DOSAGE & ADMINISTRATION SECTION.

2 DOSAGE AND ADMINISTRATION. Premedicate to reduce the risk of CRS and infusion-related reactions (IRR). (2.1, 2.3)Administer only as an intravenous infusion. (2.1, 2.6)Recommended Dosage (2.2):Dosing ScheduleDayDose of LYNOZYFICStep-Up Dosing ScheduleDay 1Step-up dose 15 mgDay 8Step-up dose 225 mgDay 15First treatment dose200 mgWeekly Dosing ScheduleOne week after Day 15 treatment dose and once weekly from Week to Week 13 for 10 treatment dosesSecond and subsequent treatment doses200 mgBiweekly (Every Weeks) Dosing ScheduleWeek 14 and every weeks thereafterSubsequent treatment doses200 mgPatients who have achieved and maintained VGPR or better at or after Week 24 and received at least 17 doses of 200 mgEvery Weeks Dosing ScheduleAt Week 24 or after and every weeks thereafterSubsequent treatment doses200 mgPatients should be hospitalized for 24 hours after administration of the first step-up dose and for 24 hours after administration of the second step-up dose. (2.1)See Full Prescribing Information for instructions on preparation and administration. (2.6). Premedicate to reduce the risk of CRS and infusion-related reactions (IRR). (2.1, 2.3). Administer only as an intravenous infusion. (2.1, 2.6). Recommended Dosage (2.2):. Patients should be hospitalized for 24 hours after administration of the first step-up dose and for 24 hours after administration of the second step-up dose. (2.1). See Full Prescribing Information for instructions on preparation and administration. (2.6). 2.1Important Administration Instructions. Administer LYNOZYFIC intravenously according to the step-up schedule to reduce the incidence and severity of cytokine release syndrome (CRS) [see Dosage and Administration (2.2)].Administer only as an intravenous infusion after dilution in 0.9% Sodium Chloride Injection [see Dosage and Administration (2.6)].Administer pretreatment medications [see Dosage and Administration (2.3)].LYNOZYFIC should be administered by healthcare provider with immediate access to emergency equipment and appropriate medical support to manage severe reactions such as cytokine release syndrome (CRS), infusion-related reactions (IRR), and neurologic toxicity, including ICANS [see Warnings and Precautions (5.1 and 5.2)].Due to the risk of CRS and neurologic toxicity, including ICANS, patients should be hospitalized for 24 hours after administration of the first step-up dose, and for 24 hours after administration of the second step-up dose.. Administer LYNOZYFIC intravenously according to the step-up schedule to reduce the incidence and severity of cytokine release syndrome (CRS) [see Dosage and Administration (2.2)].. Administer only as an intravenous infusion after dilution in 0.9% Sodium Chloride Injection [see Dosage and Administration (2.6)].. Administer pretreatment medications [see Dosage and Administration (2.3)].. LYNOZYFIC should be administered by healthcare provider with immediate access to emergency equipment and appropriate medical support to manage severe reactions such as cytokine release syndrome (CRS), infusion-related reactions (IRR), and neurologic toxicity, including ICANS [see Warnings and Precautions (5.1 and 5.2)].. Due to the risk of CRS and neurologic toxicity, including ICANS, patients should be hospitalized for 24 hours after administration of the first step-up dose, and for 24 hours after administration of the second step-up dose.. 2.2 Recommended Dosage. The recommended dosage for LYNOZYFIC is presented in Table 1. In patients who experience CRS, ICANS, or neurologic adverse reactions, refer to Tables 3, 4, and 5, respectively, for recommendations regarding administration of the next LYNOZYFIC dose. Continue treatment until disease progression or unacceptable toxicity. The recommended dosing schedule for LYNOZYFIC is provided in Table 1. The recommended dosage of LYNOZYFIC is step-up doses of mg, 25 mg, and 200 mg, followed by 200 mg weekly for 10 doses, followed by 200 mg biweekly (every weeks). In patients who have achieved and maintained VGPR or better at or after Week 24 and received at least 17 doses of 200 mg, decrease the dosing frequency to 200 mg every weeks.Table 1:LYNOZYFIC Dosing ScheduleDosing ScheduleDayWeekly doses should be at least days apart. Biweekly doses should be at least 10 days apart. Every 4-week doses should be at least 24 days apart. LYNOZYFIC DoseDuration of InfusionStep-up Dosing ScheduleDay 1Step-up dose 15 mg4 hoursDay 8Step-up dose 225 mgDay 15First treatment dose200 mgWeekly Dosing ScheduleOne week after Day 15 treatment dose and once weekly from Week to Week 13 for 10 treatment dosesSecond and subsequent treatment doses200 mg1 hour for the second treatment dose, and 30 minutes for subsequent dosesFor patients who experienced CRS with the previous dose of LYNOZYFIC, the duration of infusion should be maintained at the duration of the previous infusion; reduce the duration of infusion sequentially in subsequent doses in patients who do not experience CRS (e.g., hours, hour, then 30 minutes). Biweekly (Every Weeks) Dosing ScheduleWeek 14 and every weeks thereafterSubsequent treatment doses200 mg30 minutesPatients who have achieved and maintained VGPR or better at or after Week 24 and received at least 17 doses of 200 mgEvery Weeks Dosing ScheduleAt Week 24 or after and every weeks thereafter200 mg30 minutes. 2.3Recommended Pretreatment Medications. Administer the following pre-treatment medications before each dose of the LYNOZYFIC step-up dosing schedule, which includes step-up dose 1, step-up dose 2, and the first treatment dose, the second treatment dose, and if indicated, subsequent treatment doses (see Tables 1, 2, and 3), to reduce the risk of CRS and/or IRR [see Warnings and Precautions (5.1)]:acetaminophen (or equivalent) 650 mg to 1,000 mg orally 30 to 60 minutes prior to infusiondiphenhydramine (or equivalent) 25 mg orally or intravenously 30 to 60 minutes prior to infusiondexamethasone (or equivalent) intravenously to hours prior to infusion 40 mg dexamethasone (or equivalent) before step-up dose 1, step-up dose 2, and the first full treatment doseOnce treatment dose of LYNOZYFIC is tolerated without CRS and/or IRR with 40 mg dexamethasone (or equivalent), administer 10 mg dexamethasone (or equivalent) prior to the subsequent LYNOZYFIC treatment dose Pre-treatment medications may be discontinued once treatment dose of LYNOZYFIC is tolerated without CRS and/or IRR following pre-treatment with 10 mg dexamethasone (or equivalent), acetaminophen (or equivalent), and diphenhydramine (or equivalent) as described.. acetaminophen (or equivalent) 650 mg to 1,000 mg orally 30 to 60 minutes prior to infusion. diphenhydramine (or equivalent) 25 mg orally or intravenously 30 to 60 minutes prior to infusion. dexamethasone (or equivalent) intravenously to hours prior to infusion 40 mg dexamethasone (or equivalent) before step-up dose 1, step-up dose 2, and the first full treatment doseOnce treatment dose of LYNOZYFIC is tolerated without CRS and/or IRR with 40 mg dexamethasone (or equivalent), administer 10 mg dexamethasone (or equivalent) prior to the subsequent LYNOZYFIC treatment dose 40 mg dexamethasone (or equivalent) before step-up dose 1, step-up dose 2, and the first full treatment dose. Once treatment dose of LYNOZYFIC is tolerated without CRS and/or IRR with 40 mg dexamethasone (or equivalent), administer 10 mg dexamethasone (or equivalent) prior to the subsequent LYNOZYFIC treatment dose. 2.4Restarting LYNOZYFIC After Dosage Delay. Table provides recommendations for restarting therapy after dose delay. Refer to Table 3, Table 4, and Table for recommendations about management of CRS, ICANS, or other adverse reactions.Table 2:Recommendations for Restarting Therapy with LYNOZYFIC After Dose DelayLast Dose AdministeredTime since the last dose administeredConsider benefit-risk of restarting LYNOZYFIC in patients who require dose delay of more than 30 days. Action for next dose. (For CRS/IRR or ICANS, refer to the dose modifications in Table 3, Table 4, and Table 5.)NOTE: Administer pre-treatment medications prior to step-up dose 1, step-up dose 2, the first treatment dose, the second treatment dose, and if indicated, subsequent treatment doses [see Dosage and Administration (2.3)].5 mg14 days or lessAdminister 25 mgGreater than 14 daysRestart step-up dosing from mg25 mg14 days or lessAdminister 200 mgGreater than 14 days and less than or equal to 28 daysRestart step-up dosing from 25 mgGreater than 28 daysRestart step-up dosing from mg200 mg49 days or lessAdminister 200 mgGreater than 49 daysRestart step-up dosing from mg. 2.5Management of Adverse Reactions. Table describes the management of CRS. Table describes the management of ICANS. Table describes the management of other adverse reactions.. Cytokine Release SyndromeIdentify CRS based on clinical presentation [see Warnings and Precautions (5.1)]. Evaluate and treat other causes of fever, hypoxia, and hypotension. If CRS is suspected, withhold LYNOZYFIC until CRS resolves. CRS should be managed according to the recommendations in Table and per current practice guidelines. Supportive therapy for CRS should be administered, which may include intensive care for severe or life-threatening CRS.Table 3:Recommendations for Management of Cytokine Release SyndromeGradeBased on American Society for Transplantation and Cellular Therapy (ASTCT) criteria for grading CRS (2019). Presenting SymptomsRecommendationsGrade 1Fever >=100.4oF (38oC)Attributed to CRS. Fever may not always be present concurrently with hypotension or hypoxia as it may be masked by interventions such as steroids, antipyretics, or anticytokine therapy. Withhold LYNOZYFIC until CRS resolves.Provide supportive care, which may include intensive care.When CRS resolves, resume LYNOZYFIC.Administer pretreatment medications prior to next dose [see Dosage and Administration (2.3)]. Follow the recommendations in Table for restarting dosing. Grade 2Fever >=100.4F (38C) with:Hypotension responsive to fluids and not requiring vasopressorsand/orhypoxia requiring low-flow oxygenLow-flow oxygen defined as oxygen delivered at less than L/minute: high-flow oxygen defined as oxygen delivered at greater than or equal to L/minute. by nasal cannula or blow-byWithhold LYNOZYFIC until CRS resolves.Provide supportive care, which may include intensive care.When CRS resolves, resume treatment with LYNOZYFIC. Consider decrease in infusion rate up to 50% (no more than hours total) when resuming treatment. Increase rate on subsequent infusions if tolerated.Monitor patients within proximity of healthcare facility for 24 hours following this dose, and consider hospitalization. Grade 3Fever >=100.4F (38C) with: Hypotension requiring vasopressor (with or without vasopressin) and/or hypoxia requiring high-flow oxygen by nasal cannula, face mask, non-rebreather mask, or Venturi mask.Withhold LYNOZYFIC until CRS resolves.Provide supportive care, which may include intensive care.When CRS resolves, resume treatment with LYNOZYFIC at reduced dose: If the last dose administered was mg, administer 2.5 mg. If the last dose administered was 25 mg, restart step-up dosing from mg. If the last dose administered was 200 mg, refer to Table for recommendations regarding restarting therapy based on time since the last dose. Decrease infusion rate up to 50% (no more than hours total).Hospitalize for 24 hours after the administration for this dose. After resuming treatment, if the administered dose is tolerated:Continue with the next dose of the recommended dosing regimen per Table 1.If the full dose is tolerated, infusion rate can be increased to the rate prior to the adverse reaction. Permanently discontinue LYNOZYFIC if Grade CRS recurs with subsequent infusions.Grade 4Fever >=100.4F (38C) with: Hypotension requiring multiple vasopressors (excluding vasopressin) and/or hypoxia requiring oxygen by positive pressure (e.g., continuous positive airway pressure (CPAP), bilevel positive airway pressure (BiPAP), intubation, and mechanical ventilation).Discontinue LYNOZYFIC permanently.CRS should be managed per Grade recommendations.OtherAST/ALT greater than times ULN associated with CRS Grade or lessWithhold LYNOZYFIC until CRS resolves and AST/ALT are less than times ULN if baseline was normal or 1.5 to times baseline if baseline was abnormal.Provide supportive care, which may include intensive care, and monitor.No change in dose is needed in patients without CRS symptoms with transaminase levels that are trending towards baseline within days.If values do not trend towards baseline in days, decrease the dose. See infusion rate information by CRS grade.. Withhold LYNOZYFIC until CRS resolves.. Provide supportive care, which may include intensive care.. When CRS resolves, resume LYNOZYFIC.Administer pretreatment medications prior to next dose [see Dosage and Administration (2.3)]. Follow the recommendations in Table for restarting dosing. Withhold LYNOZYFIC until CRS resolves.. Provide supportive care, which may include intensive care.. When CRS resolves, resume treatment with LYNOZYFIC. Consider decrease in infusion rate up to 50% (no more than hours total) when resuming treatment. Increase rate on subsequent infusions if tolerated.Monitor patients within proximity of healthcare facility for 24 hours following this dose, and consider hospitalization. Consider decrease in infusion rate up to 50% (no more than hours total) when resuming treatment. Increase rate on subsequent infusions if tolerated.. Monitor patients within proximity of healthcare facility for 24 hours following this dose, and consider hospitalization.. Withhold LYNOZYFIC until CRS resolves.. Provide supportive care, which may include intensive care.. When CRS resolves, resume treatment with LYNOZYFIC at reduced dose: If the last dose administered was mg, administer 2.5 mg. If the last dose administered was 25 mg, restart step-up dosing from mg. If the last dose administered was 200 mg, refer to Table for recommendations regarding restarting therapy based on time since the last dose. Decrease infusion rate up to 50% (no more than hours total).Hospitalize for 24 hours after the administration for this dose. Decrease infusion rate up to 50% (no more than hours total).. Hospitalize for 24 hours after the administration for this dose.. After resuming treatment, if the administered dose is tolerated:Continue with the next dose of the recommended dosing regimen per Table 1.If the full dose is tolerated, infusion rate can be increased to the rate prior to the adverse reaction. Continue with the next dose of the recommended dosing regimen per Table 1.. If the full dose is tolerated, infusion rate can be increased to the rate prior to the adverse reaction.. Permanently discontinue LYNOZYFIC if Grade CRS recurs with subsequent infusions.. Discontinue LYNOZYFIC permanently.. CRS should be managed per Grade recommendations.. Withhold LYNOZYFIC until CRS resolves and AST/ALT are less than times ULN if baseline was normal or 1.5 to times baseline if baseline was abnormal.. Provide supportive care, which may include intensive care, and monitor.. No change in dose is needed in patients without CRS symptoms with transaminase levels that are trending towards baseline within days.. If values do not trend towards baseline in days, decrease the dose. See infusion rate information by CRS grade.. Neurologic Toxicity, including ICANSManagement recommendations for ICANS and neurologic toxicity are summarized in Table and Table 5. At the first sign of suspected neurologic toxicity, including ICANS, withhold LYNOZYFIC and consider consultation with neurologist and other specialists for further evaluation and management. Rule out other causes of neurologic symptoms. Provide supportive therapy, which may include intensive care for severe or life-threatening ICANS. Manage per current practice guidelines.Table 4:Recommendations for Management of ICANSGradeBased on American Society for Transplantation and Cellular Therapy (ASTCT) 2019 grading for ICANS. Presenting SymptomsManagement is determined by the most severe event, not attributable to any other cause. RecommendationsGrade 1ICEIf patient is arousable and able to perform Immune Effector Cell-Associated Encephalopathy (ICE) Assessment, assess: Orientation (oriented to year, month, city, hospital=4 points); Naming (name objects, e.g., point to clock, pen, button=3 points); Following Commands (e.g., show me fingers or close your eyes and stick out your tongue=1 point); Writing (ability to write standard sentence=1 point); and Attention (count backwards from 100 by ten=1 point). If patient is unarousable and unable to perform ICE Assessment (Grade ICANS)=0 points. score 7-9, or depressed level of consciousnessNot attributable to any other cause.: awakens spontaneously.Withhold until neurologic symptoms resolve or return to baseline.Follow the recommendations in Table for restarting dosing. Provide supportive therapy. Manage per current practice guidelines.Consider non-sedating, anti-seizure medications for seizure prophylaxis.Grade 2ICE score 3-6, or depressed level of consciousness: awakens to voice.Withhold until neurologic symptoms resolve or return to baseline. Provide supportive therapy. Manage per current practice guidelines.Administer dexamethasoneAll references to dexamethasone administration are dexamethasone or equivalent. 10 mg intravenously every hours. Continue dexamethasone use until resolution to Grade or less, then taper.Consider non-sedating, anti-seizure medications for seizure prophylaxis.Monitor patients within proximity of healthcare facility for 24 hours following the next dose of LYNOZYFIC and consider hospitalization.Grade 3ICE score 0-2, or depressed level of consciousness: awakens only to tactile stimulus, or seizures, either:any clinical seizure, focal or generalized, that resolves rapidly, ornon-convulsive seizures on electroencephalogram (EEG) that resolve with intervention,or raised intracranial pressure: focal/local edema on neuroimaging.Withhold until neurologic symptoms resolve or return to baseline.Provide supportive therapy, which may include intensive care. Manage per current practice guidelines.Consider neurology evaluation.Administer dexamethasone 10 mg intravenously every hours. Continue dexamethasone use until resolution to Grade or less, then taper.Consider non-sedating, anti-seizure medications for seizure prophylaxis.Permanently discontinue LYNOZYFIC for recurrent Grade ICANS.Resume treatment with LYNOZYFIC at reduced doseIf the last dose administered was mg, administer 2.5 mg. If the last dose administered was 25 mg, restart step-up dosing from mg. If the last dose administered was 200 mg, refer to Table for recommendations regarding restarting therapy based on time since the last dose. and hospitalize for 24 hours after the administration of the dose. After resuming treatment, if the administered dose is tolerated, continue with the next dose of the recommended dosing regimen per Table 1.Grade 4ICE score 0, or depressed level of consciousness: either:patient is unarousable or requires vigorous or repetitive tactile stimuli to arouse, orstupor or coma,or seizures, either:life-threatening prolonged seizure (>5 minutes), orrepetitive clinical or electrical seizures without return to baseline in between,or motor findings:deep focal motor weakness such as hemiparesis or paraparesis,or raised intracranial pressure/cerebral edema, with signs/ symptoms such as:diffuse cerebral edema on neuroimaging, ordecerebrate or decorticate posturing, orcranial nerve VI palsy, orpapilledema, orCushings triad. Permanently discontinue LYNOZYFIC.Provide supportive therapy, which may include intensive care. Manage per current practice guidelines.Consider neurology evaluation.Administer dexamethasone 10 mg intravenously every hours. Continue dexamethasone use until resolution to Grade or less, then taper.Consider non-sedating, anti-seizure medications for seizure prophylaxis.. Withhold until neurologic symptoms resolve or return to baseline.Follow the recommendations in Table for restarting dosing. Provide supportive therapy. Manage per current practice guidelines.. Consider non-sedating, anti-seizure medications for seizure prophylaxis.. Withhold until neurologic symptoms resolve or return to baseline. Provide supportive therapy. Manage per current practice guidelines.. Administer dexamethasoneAll references to dexamethasone administration are dexamethasone or equivalent. 10 mg intravenously every hours. Continue dexamethasone use until resolution to Grade or less, then taper.. Consider non-sedating, anti-seizure medications for seizure prophylaxis.. Monitor patients within proximity of healthcare facility for 24 hours following the next dose of LYNOZYFIC and consider hospitalization.. any clinical seizure, focal or generalized, that resolves rapidly, or. non-convulsive seizures on electroencephalogram (EEG) that resolve with intervention,. Withhold until neurologic symptoms resolve or return to baseline.. Provide supportive therapy, which may include intensive care. Manage per current practice guidelines.. Consider neurology evaluation.. Administer dexamethasone 10 mg intravenously every hours. Continue dexamethasone use until resolution to Grade or less, then taper.. Consider non-sedating, anti-seizure medications for seizure prophylaxis.. Permanently discontinue LYNOZYFIC for recurrent Grade ICANS.. Resume treatment with LYNOZYFIC at reduced doseIf the last dose administered was mg, administer 2.5 mg. If the last dose administered was 25 mg, restart step-up dosing from mg. If the last dose administered was 200 mg, refer to Table for recommendations regarding restarting therapy based on time since the last dose. and hospitalize for 24 hours after the administration of the dose. After resuming treatment, if the administered dose is tolerated, continue with the next dose of the recommended dosing regimen per Table 1.. patient is unarousable or requires vigorous or repetitive tactile stimuli to arouse, or. stupor or coma,. life-threatening prolonged seizure (>5 minutes), or. repetitive clinical or electrical seizures without return to baseline in between,. deep focal motor weakness such as hemiparesis or paraparesis,. diffuse cerebral edema on neuroimaging, or. decerebrate or decorticate posturing, or. cranial nerve VI palsy, or. papilledema, or. Cushings triad.. Permanently discontinue LYNOZYFIC.. Provide supportive therapy, which may include intensive care. Manage per current practice guidelines.. Consider neurology evaluation.. Administer dexamethasone 10 mg intravenously every hours. Continue dexamethasone use until resolution to Grade or less, then taper.. Consider non-sedating, anti-seizure medications for seizure prophylaxis.. Other Adverse ReactionsManagement recommendations for other adverse reactions are summarized in Table 5.Table 5:Recommendations for Management of Other Adverse ReactionsAdverse ReactionSeverityBased on National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE), Version 5.0 RecommendationsInfusion-Related ReactionsGrade 2Stop infusion and treat symptoms.May resume treatment with the remaining infusion (total infusion time must not exceed hours total) when symptoms are Grade or baseline.Consider decreasing infusion rate by up to 50% when resuming treatment. If tolerated, infusion rate can be increased with subsequent doses.Grade 3Stop infusion and treat symptoms.May resume when symptoms are Grade or baseline.After resolution of the adverse event, follow the recommendations:Decrease the infusion rate up to 50% (no more than hours total).Resume at reduced dose.If the last dose administered was mg, administer 2.5 mg. If the last dose administered was 25 mg, restart step-up dosing from mg. If the last dose administered was 200 mg, refer to Table for recommendations regarding restarting therapy based on time since the last dose. If the administered dose is tolerated, continue with the next dose of the recommended dosing regimen at the decreased infusion rate.Infusion rate can be increased if tolerated. Permanently discontinue LYNOZYFIC if Grade IRR recurs with subsequent infusions.Grade 4Permanently discontinue LYNOZYFIC and treat symptoms.Neurologic Adverse Reactions (excluding ICANS)Grade 2Withhold LYNOZYFIC until symptoms resolve to Grade or baseline.Follow the recommendations in Table for restarting dosing. Grade (First occurrence)Withhold LYNOZYFIC until Grade or baseline. Grade (Recurrent)Grade 4Permanently discontinue LYNOZYFIC.InfectionsGrades or 3Withhold LYNOZYFIC in patients with active infection until the infection improves to Grade or less. Grade 4Consider permanent discontinuation of LYNOZYFIC. If treatment is not permanently discontinued, withhold subsequent treatment doses until Grade or baseline. Other Non-hematologic Adverse ReactionsGrade 3Withhold LYNOZYFIC until Grade or baseline. Grade 4Consider permanent discontinuation of LYNOZYFIC.If LYNOZYFIC is not permanently discontinued, withhold subsequent treatment doses until Grade or baseline. Hematologic Adverse ReactionsPlatelet count less than 50,000/mcL with bleeding ORless than 25,000/mcLWithhold LYNOZYFIC until 25,000/mcL or higher and no evidence of bleeding. Absolute neutrophil count less than x 109/L with Grade or higher infection OR less than 0.5 109/LWithhold LYNOZYFIC until 0.5 109/L or higher. Febrile neutropeniaWithhold LYNOZYFIC until neutrophil count is greater than x 109/L and fever resolves. Hemoglobin less than g/dLWithhold LYNOZYFIC until hemoglobin is g/dL or higher. Stop infusion and treat symptoms.. May resume treatment with the remaining infusion (total infusion time must not exceed hours total) when symptoms are Grade or baseline.. Consider decreasing infusion rate by up to 50% when resuming treatment. If tolerated, infusion rate can be increased with subsequent doses.. Stop infusion and treat symptoms.. May resume when symptoms are Grade or baseline.. After resolution of the adverse event, follow the recommendations:Decrease the infusion rate up to 50% (no more than hours total).Resume at reduced dose.If the last dose administered was mg, administer 2.5 mg. If the last dose administered was 25 mg, restart step-up dosing from mg. If the last dose administered was 200 mg, refer to Table for recommendations regarding restarting therapy based on time since the last dose. If the administered dose is tolerated, continue with the next dose of the recommended dosing regimen at the decreased infusion rate.Infusion rate can be increased if tolerated. Decrease the infusion rate up to 50% (no more than hours total).. Resume at reduced dose.If the last dose administered was mg, administer 2.5 mg. If the last dose administered was 25 mg, restart step-up dosing from mg. If the last dose administered was 200 mg, refer to Table for recommendations regarding restarting therapy based on time since the last dose. If the administered dose is tolerated, continue with the next dose of the recommended dosing regimen at the decreased infusion rate.. Infusion rate can be increased if tolerated.. Permanently discontinue LYNOZYFIC if Grade IRR recurs with subsequent infusions.. Permanently discontinue LYNOZYFIC and treat symptoms.. Withhold LYNOZYFIC until symptoms resolve to Grade or baseline.Follow the recommendations in Table for restarting dosing. Withhold LYNOZYFIC until Grade or baseline. Permanently discontinue LYNOZYFIC.. Withhold LYNOZYFIC in patients with active infection until the infection improves to Grade or less. Consider permanent discontinuation of LYNOZYFIC. If treatment is not permanently discontinued, withhold subsequent treatment doses until Grade or baseline. Withhold LYNOZYFIC until Grade or baseline. Consider permanent discontinuation of LYNOZYFIC.. If LYNOZYFIC is not permanently discontinued, withhold subsequent treatment doses until Grade or baseline. Withhold LYNOZYFIC until 25,000/mcL or higher and no evidence of bleeding. Withhold LYNOZYFIC until 0.5 109/L or higher. Withhold LYNOZYFIC until neutrophil count is greater than x 109/L and fever resolves. Withhold LYNOZYFIC until hemoglobin is g/dL or higher. 2.6Preparation and Administration. PreparationUse aseptic technique to prepare LYNOZYFIC. Each vial is intended for one time use only. Do not shake.Parenteral drug products should be inspected visually for particulate matter and discoloration prior to administration, whenever solution and container permit. LYNOZYFIC is clear to slightly opalescent, colorless to pale yellow solution. Discard the vial if the solution is cloudy, discolored, or contains particulate matter.Determine the dose, total volume of LYNOZYFIC solution, and the number of LYNOZYFIC vials needed (see Table 6).. Use aseptic technique to prepare LYNOZYFIC. Each vial is intended for one time use only. Do not shake.. Parenteral drug products should be inspected visually for particulate matter and discoloration prior to administration, whenever solution and container permit. LYNOZYFIC is clear to slightly opalescent, colorless to pale yellow solution. Discard the vial if the solution is cloudy, discolored, or contains particulate matter.. Determine the dose, total volume of LYNOZYFIC solution, and the number of LYNOZYFIC vials needed (see Table 6).. DilutionWithdraw the desired dose from the vial of LYNOZYFIC and transfer into an intravenous infusion bag [polyvinyl chloride (PVC) or polyolefin (PO)] of 0.9% Sodium Chloride Injection, according to Table 6. Discard any unused portion left in the vial. Mix diluted solution by gentle inversion. Do not shake the solution. Table 6:Dilution of LYNOZYFICLYNOZYFIC doseLYNOZYFIC vial strengthVolume of LYNOZYFIC to be added to the infusion bagSize of 0.9% Sodium Chloride Injection Infusion Bag (PVC or PO)2.5 mgModified dose due to adverse reaction. For instructions on when to use the modified dose refer to Table 3, Table 4, and Table 5. mg/2.5 mL1.25 mL50 mL5 mg5 mg/2.5 mL2.5 mL50 mL or 100 mL25 mg5 mg/2.5 mL12.5 mL50 mL or 100 mL200 mg200 mg/10 mL10 mL50 mL or 100 mL. Withdraw the desired dose from the vial of LYNOZYFIC and transfer into an intravenous infusion bag [polyvinyl chloride (PVC) or polyolefin (PO)] of 0.9% Sodium Chloride Injection, according to Table 6. Discard any unused portion left in the vial. Mix diluted solution by gentle inversion. Do not shake the solution. Diluted LYNOZYFIC StorageUse diluted LYNOZYFIC immediately. If not used immediately, store the solution:at room temperature up to 25C (77F) for no more than hours from preparation to the start of the infusion.Orunder refrigeration at 2C to 8C (36F to 46F) for no more than 48 hours from preparation to the start of the infusion.Do not freeze.Do not shake.. at room temperature up to 25C (77F) for no more than hours from preparation to the start of the infusion.Or. under refrigeration at 2C to 8C (36F to 46F) for no more than 48 hours from preparation to the start of the infusion.. AdministrationAdminister as an intravenous infusion only.Refer to Dosage and Administration (2.2) for infusion rates.Connect the prepared intravenous infusion bag containing the final LYNOZYFIC solution to intravenous tubing constructed of PVC, polyethylene (PE)-lined PVC, or polyurethane (PU). Use of 0.2-micron to 5-micron polyethersulfone (PES) filter is required.Prime with LYNOZYFIC to the end of the intravenous tubing.Do not mix LYNOZYFIC with other drugs or concurrently administer other drugs through the same intravenous line.Upon completion of LYNOZYFIC infusion, flush the infusion line with an adequate volume of sterile 0.9% Sodium Chloride Injection to ensure that the entire contents of the infusion bag are administered. Total infusion time should include flushing of the infusion line.. Administer as an intravenous infusion only.. Refer to Dosage and Administration (2.2) for infusion rates.. Connect the prepared intravenous infusion bag containing the final LYNOZYFIC solution to intravenous tubing constructed of PVC, polyethylene (PE)-lined PVC, or polyurethane (PU). Use of 0.2-micron to 5-micron polyethersulfone (PES) filter is required.. Prime with LYNOZYFIC to the end of the intravenous tubing.. Do not mix LYNOZYFIC with other drugs or concurrently administer other drugs through the same intravenous line.. Upon completion of LYNOZYFIC infusion, flush the infusion line with an adequate volume of sterile 0.9% Sodium Chloride Injection to ensure that the entire contents of the infusion bag are administered. Total infusion time should include flushing of the infusion line.

PACKAGE LABEL.PRINCIPAL DISPLAY PANEL.

PRINCIPAL DISPLAY PANEL 5 mg 2.5 mL Vial Carton. NDC 61755-054-01 Rx onlyLYNOZYFIC(TM)(linvoseltamab-gcpt) Injection5 mg 2.5 mL (2 mg/mL)For Intravenous Infusion after DilutionSingle-Dose Vial. Discard unused portion.ATTENTION: Dispense the enclosed Medication Guideto each patient.One 2.5 mL Vial REGENERON. PRINCIPAL DISPLAY PANEL 5 mg 2.5 mL Vial Carton.

PEDIATRIC USE SECTION.

8.4 Pediatric Use. The safety and effectiveness of LYNOZYFIC have not been established in pediatric patients.

ADVERSE REACTIONS SECTION.

6 ADVERSE REACTIONS. The following clinically significant adverse reactions are described elsewhere in the labeling:Cytokine Release Syndrome [see Warnings and Precautions (5.1)] Neurologic Toxicity, including Immune Effector Cell-Associated Neurotoxicity Syndrome [see Warnings and Precautions (5.2)] Infections [see Warnings and Precautions (5.4)] Neutropenia [see Warnings and Precautions (5.5)] Hepatotoxicity [see Warnings and Precautions (5.6)] Cytokine Release Syndrome [see Warnings and Precautions (5.1)] Neurologic Toxicity, including Immune Effector Cell-Associated Neurotoxicity Syndrome [see Warnings and Precautions (5.2)] Infections [see Warnings and Precautions (5.4)] Neutropenia [see Warnings and Precautions (5.5)] Hepatotoxicity [see Warnings and Precautions (5.6)] The most common adverse reactions (>=20%) are musculoskeletal pain, cytokine release syndrome, cough, upper respiratory tract infection, diarrhea, fatigue, pneumonia, nausea, headache, and dyspnea. (6.1)The most common Grade or laboratory abnormalities (>=30%) are decreased lymphocyte count, decreased neutrophil count, decreased hemoglobin, and decreased white blood cell count. (6.1)To report SUSPECTED ADVERSE REACTIONS, contact Regeneron at 1-844-467-2998 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.. 6.1 Clinical Trials Experience. Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice.. Relapsed or Refractory Multiple MyelomaThe safety of LYNOZYFIC was evaluated in LINKER-MM1 [see Clinical Studies (14)]. Patients (n=117) received LYNOZYFIC as step-up doses of mg on Day and 25 mg on Day 8, and the first treatment dose of 200 mg on Day 15. Patients then received 200 mg intravenously once weekly from Week to Week 13, followed by 200 mg every weeks from Week 14. In the Phase portion of the study, patients who achieved and maintained VGPR or better at or after Week 24 and received at least 17 doses of 200 mg were able to receive every 4-week dosing. The median duration of treatment was 47 weeks (range 1, 151); 55% of patients were exposed for months or longer and 36% were exposed for year or longer.The median age of patients who received LYNOZYFIC was 70 years (range: 37 to 91 years); 55% were male; 71% were White, 17% were Black or African American, and 9% were Asian.Serious adverse reactions occurred in 74% of patients who received LYNOZYFIC. Serious adverse reactions that occurred in >5% of patients included cytokine release syndrome (27%), pneumonia (13%), COVID-19 (7%), and acute kidney injury (5%). Fatal adverse reactions occurred in 7% of patients, and included sepsis (3.4%), chronic kidney disease (0.9%), pneumonia (0.9%), tumor lysis syndrome (0.9%), and encephalopathy (0.9%).Permanent discontinuation of LYNOZYFIC due to adverse reactions occurred in 16% of patients. Adverse reactions leading to discontinuation that occurred in at least patients included sepsis, pneumonia, and encephalopathy.Dosage interruptions or delays of LYNOZYFIC due to adverse reactions occurred in 74% of patients. Adverse reactions which required dosage interruption or delay in >10% of patients included neutropenia (29%), upper respiratory tract infection (18%), pneumonia (15%), and COVID-19 infection (11%).The most common adverse reactions (>=20%) were musculoskeletal pain, cytokine release syndrome, cough, upper respiratory tract infection, diarrhea, fatigue, pneumonia, nausea, headache, and dyspnea. The most common Grade to laboratory abnormalities (>=30%) were decreased lymphocyte count, decreased neutrophil count, decreased hemoglobin, and decreased white blood cell count.Table summarizes the adverse reactions in LINKER-MM1.Table 7:Adverse Reactions (>=10%) in Patients with Relapsed or Refractory Multiple Myeloma Who Received LYNOZYFIC in LINKER-MM1Adverse ReactionLYNOZYFIC (N=117)All Grades (%)Grade or (%)Musculoskeletal and connective tissue disorders Musculoskeletal painIncludes other related terms. 533.4Only Grade adverse reactions occurred. Immune system disorders Cytokine release syndrome460.9 Hypogammaglobulinemia130.9 Respiratory, thoracic and mediastinal disorders Cough 390 Dyspnea 210.9 Nasal congestion160Infections and infestations Upper respiratory tract infection 356 PneumoniaPneumonia includes atypical pneumonia, COVID-19 pneumonia, PJP, pneumonia, pneumonia cytomegaloviral, pneumonia fungal, pneumonia influenzal, and pneumonia viral. Includes fatal outcome. 2821 COVID-19175 Urinary tract infections 168 Sepsis106Gastrointestinal disorders Diarrhea351.7 Nausea230 Vomiting190 Constipation170General disorders and administration site conditions Fatigue 340 Edema 190.9 Pyrexia170Nervous system disorders Headache 220.9 Encephalopathy Encephalopathy includes agitation, amnesia, cognitive disorder, confusional state, delirium, depressed level of consciousness, encephalopathy (including hyperammonemic and toxic encephalopathy), irritability, lethargy, memory impairment, mental status changes, somnolence, and excludes ICANS. 183.4 Sensory Neuropathy 130.9Metabolism and nutrition disorders Decreased appetite150.9 Skin and subcutaneous tissue disorders RashRash includes dermatitis acneiform, dermatitis contact, drug eruption, erythema, rash, rash erythematous, rash maculo-papular, rash pruritic, and stasis dermatitis. 151.7 Psychiatric disorders Insomnia130Vascular disorders Hypertension104.3 Clinically significant adverse reactions that occurred in <10% of patients treated with LYNOZYFIC included IRR, motor dysfunction, febrile neutropenia, ICANS, CMV infection, and PML.Table summarizes the laboratory abnormalities in LINKER-MM1.Table 8:Select Laboratory Abnormalities (>=5% for Grade or 4) That Worsened from Baseline in Patients with Multiple Myeloma Treated with LYNOZYFIC in LINKER-MM1Laboratory AbnormalityLaboratory tests were graded according to NCI-CTCAE (National Cancer Institute Common Terminology Criteria for Adverse Events) Version 5.0. LYNOZYFIC (N=117)The denominator used to calculate the rate varied from 106 to 117 based on the number of patients with baseline value and at least one post-treatment value. All Grades (%)Grades or (%)Hematology Lymphocyte count decreased9792 Hemoglobin decreased7242 Platelet count decreased6419 White blood cell count decreased6331 Neutrophil count decreased6247Chemistry Aspartate aminotransferase increased6110 Phosphorus decreased5524 Creatinine increased477 Alanine aminotransferase increased466.

BOXED WARNING SECTION.

WARNING: CYTOKINE RELEASE SYNDROME AND NEUROLOGIC TOXICITY, INCLUDING IMMUNE EFFECTOR CELL-ASSOCIATED NEUROTOXICITY SYNDROME. Cytokine release syndrome (CRS), including serious or life-threatening reactions, can occur in patients receiving LYNOZYFIC. Initiate treatment with LYNOZYFIC step-up dosing to reduce the risk of CRS. Manage CRS, withhold LYNOZYFIC until CRS resolves, and modify the next dose or permanently discontinue based on severity [see Dosage and Administration (2.2, 2.4, 2.5) and Warnings and Precautions (5.1)]. Neurologic toxicity, including immune effector cell-associated neurotoxicity syndrome (ICANS), including serious or life-threatening reactions, can occur in patients receiving LYNOZYFIC. Monitor patients for signs or symptoms of neurologic toxicity, including ICANS during treatment. Manage neurologic toxicity, including ICANS, withhold LYNOZYFIC until neurologic toxicity, including ICANS resolves, and modify the next dose or permanently discontinue based on severity [see Dosage and Administration (2.2, 2.4, 2.5) and Warnings and Precautions (5.2)]. Because of the risk of CRS and neurologic toxicity, including ICANS, LYNOZYFIC is available only through restricted program under Risk Evaluation and Mitigation Strategy (REMS) called the LYNOZYFIC REMS [see Warnings and Precautions (5.3)]. Cytokine release syndrome (CRS), including serious or life-threatening reactions, can occur in patients receiving LYNOZYFIC. Initiate treatment with LYNOZYFIC step-up dosing to reduce the risk of CRS. Manage CRS, withhold LYNOZYFIC until CRS resolves, and modify the next dose or permanently discontinue based on severity [see Dosage and Administration (2.2, 2.4, 2.5) and Warnings and Precautions (5.1)]. Neurologic toxicity, including immune effector cell-associated neurotoxicity syndrome (ICANS), including serious or life-threatening reactions, can occur in patients receiving LYNOZYFIC. Monitor patients for signs or symptoms of neurologic toxicity, including ICANS during treatment. Manage neurologic toxicity, including ICANS, withhold LYNOZYFIC until neurologic toxicity, including ICANS resolves, and modify the next dose or permanently discontinue based on severity [see Dosage and Administration (2.2, 2.4, 2.5) and Warnings and Precautions (5.2)]. Because of the risk of CRS and neurologic toxicity, including ICANS, LYNOZYFIC is available only through restricted program under Risk Evaluation and Mitigation Strategy (REMS) called the LYNOZYFIC REMS [see Warnings and Precautions (5.3)]. WARNING: CYTOKINE RELEASE SYNDROME and NEUROLOGIC TOXICITY, including IMMUNE EFFECTOR CELL-ASSOCIATED NEUROTOXICITY SYNDROMESee full prescribing information for complete boxed warning.Cytokine release syndrome (CRS), including serious or life-threatening reactions, can occur in patients receiving LYNOZYFIC. Initiate treatment with LYNOZYFIC step-up dosing to reduce the risk of CRS. Manage CRS, withhold LYNOZYFIC until CRS resolves and modify the next dose or permanently discontinue based on severity. (2.2, 2.4, 2.5, 5.1)Neurologic Toxicity, including immune effector cell-associated neurotoxicity syndrome (ICANS), including serious or life-threatening reactions, can occur in patients receiving LYNOZYFIC. Monitor patients for signs or symptoms of neurologic toxicity, including ICANS during treatment. Manage neurologic toxicity, including ICANS, withhold LYNOZYFIC until neurologic toxicity, including ICANS resolves and modify the next dose or permanently discontinue based on severity. (2.2, 2.4, 2.5, 5.2)LYNOZYFIC is available only through restricted program called the LYNOZYFIC Risk Evaluation and Mitigation Strategy (REMS). (5.3). Cytokine release syndrome (CRS), including serious or life-threatening reactions, can occur in patients receiving LYNOZYFIC. Initiate treatment with LYNOZYFIC step-up dosing to reduce the risk of CRS. Manage CRS, withhold LYNOZYFIC until CRS resolves and modify the next dose or permanently discontinue based on severity. (2.2, 2.4, 2.5, 5.1). Neurologic Toxicity, including immune effector cell-associated neurotoxicity syndrome (ICANS), including serious or life-threatening reactions, can occur in patients receiving LYNOZYFIC. Monitor patients for signs or symptoms of neurologic toxicity, including ICANS during treatment. Manage neurologic toxicity, including ICANS, withhold LYNOZYFIC until neurologic toxicity, including ICANS resolves and modify the next dose or permanently discontinue based on severity. (2.2, 2.4, 2.5, 5.2). LYNOZYFIC is available only through restricted program called the LYNOZYFIC Risk Evaluation and Mitigation Strategy (REMS). (5.3).

CARCINOGENESIS & MUTAGENESIS & IMPAIRMENT OF FERTILITY SECTION.

13.1Carcinogenesis, Mutagenesis, Impairment of Fertility. No carcinogenicity or genotoxicity studies have been conducted with linvoseltamab-gcpt.No animal studies have been performed to evaluate the effects of linvoseltamab-gcpt on fertility.

CLINICAL PHARMACOLOGY SECTION.

12 CLINICAL PHARMACOLOGY. 12.1Mechanism of Action. Linvoseltamab-gcpt is bispecific T-cell engaging antibody that binds to the CD3 receptor expressed on the surface of T-cells and B-cell maturation antigen (BCMA) expressed on the surface of multiple myeloma cells and some healthy B-lineage cells.In vitro, linvoseltamab-gcpt activated T-cells, caused the release of various proinflammatory cytokines, and resulted in the lysis of multiple myeloma cells. Linvoseltamab-gcpt had anti-tumor activity in mouse models of multiple myeloma.. 12.2 Pharmacodynamics. The 200 mg once weekly dosing regimen was associated with better objective response rate and complete response rate when compared to the 50 mg once weekly (0.25 times the recommended dosage) dosing regimen in patients with relapsed or refractory multiple myeloma.Linvoseltamab-gcpt exposure-response relationships have not been fully characterized.. Effect on Circulating CytokinesTransient elevation of circulating cytokines (IL-2, IL-6, and IFN-) was primarily observed during the step-up dose regimen and the first full 200 mg dose. The highest elevation of cytokines was generally observed hours after each infusion and generally returned to baseline prior to the next dose. Limited cytokine release was observed following subsequent doses.. 12.3 Pharmacokinetics. Pharmacokinetic (PK) parameters were evaluated at the recommended dosage in patients with relapsed or refractory multiple myeloma and are presented as geometric mean (CV%) unless otherwise specified.Linvoseltamab-gcpt PK exposures following use of the recommended dosing schedule are presented in Table 9. Linvoseltamab-gcpt Ctrough increased more than proportionally over dose range of 96 mg to 800 mg (0.48 to times the recommended full dose). Linvoseltamab-gcpt maximum concentration (127 mg/L [51%]) is achieved after the first dose of the every-2-weeks dosing regimen (i.e., the 12th dose of 200 mg).Table 9:Geometric Mean (CV%) Exposure Following the Recommended Dosage for Linvoseltamab-gcptDosing PeriodCmax (mg/L)Ctrough (mg/L)Cavg (mg /L)First 200 mg weekly dose52.7 (37.2)15.5 (64.8)27.4 (34.2)End of 200 mg weekly dosing (11th dose of 200 mg)124 (50.4)61.8 (123)84.6 (74.6)End of 200 mg every weeks dosing (16th dose of 200 mg)97.9 (52.7)30.2 (213)51.9 (95.3)Steady stateSteady state values are approximated at Week 28. with 200 mg every weeks dosing64.8 (45.1)6.3 (362)20.5 (84.6). DistributionLinvoseltamab-gcpt volume of distribution (Vd) is 7.05 (33.6%).. EliminationLinvoseltamab-gcpt clearance is 0.68 L/day (52.2%) at baseline and 0.43 L/day (83.8%) at steady state.Linvoseltamab-gcpt clearance decreases over time because its elimination is mediated by two parallel processes: linear, non-saturable catabolic process and nonlinear, saturable target-mediated pathway. Patients who discontinue linvoseltamab-gcpt are expected to have 97% reduction from Cmax at median (5th to 95th percentile) time of 77.7 (18 to 154) days after last dose.. MetabolismLinvoseltamab-gcpt is expected to be metabolized into small peptides by catabolic pathways.. Specific PopulationsNo clinically significant differences in the pharmacokinetics of linvoseltamab-gcpt were observed based on age (37 to 91 years), weight (44 to 172 kg), sex, race (White, Asian, or Black), ethnicity (Hispanic/Latino or not Hispanic/Latino), mild to moderate renal impairment (creatinine clearance [CrCL] 30 to 89 mL/min, by Cockcroft-Gault [C-G] equation), or mild hepatic impairment (total bilirubin less than or equal to upper limit of normal [ULN] with AST greater than ULN or total bilirubin greater than to 1.5 times ULN with any AST).The effect of severe renal impairment (CrCL 15 to 29 mL/min), end-stage renal disease (CrCL less than 15 mL/min), and moderate to severe hepatic impairment (total bilirubin greater than 1.5 times ULN with any AST) on the pharmacokinetics of linvoseltamab-gcpt is unknown.. 12.6Immunogenicity. The observed incidence of anti-drug antibodies is highly dependent on the sensitivity and specificity of the assay. Differences in assay methods preclude meaningful comparisons of the incidence of anti-drug antibodies in the study described below with the incidence of anti-drug antibodies in other studies, including those of linvoseltamab-gcpt.During treatment in LINKER-MM1 (evaluated through 30 months) [see Clinical Studies (14)], 1% (2/192) of LYNOZYFIC-treated patients developed anti-linvoseltamab-gcpt antibodies. Because of the low occurrence of anti-drug antibodies, the effect of these antibodies on the pharmacokinetics, pharmacodynamics, safety, and/or effectiveness of linvoseltamab products is unknown.

CLINICAL STUDIES SECTION.

14 CLINICAL STUDIES. 14.1Relapsed or Refractory Multiple Myeloma. The efficacy of LYNOZYFIC was evaluated in patients with relapsed or refractory multiple myeloma in an open-label, multi-center, multi-cohort study: LINKER-MM1 (NCT03761108). The study included patients who had previously received at least prior therapies, including proteasome inhibitor (PI), an immunomodulatory agent (IMiD), and an anti-CD38 antibody. The study included patients with Eastern Cooperative Oncology Group (ECOG) score of or and adequate baseline hematologic (absolute neutrophil count 1 109/L, platelet count 50 109/L, hemoglobin level >8 g/dL), renal (CrCL 30 mL/min), and hepatic (AST and ALT <= 2.5 ULN, total bilirubin <= 1.5 ULN, alkaline phosphatase <= 2.5 ULN) function.The study excluded patients with known multiple myeloma brain lesions or meningeal involvement, history of neurodegenerative condition, history of seizure within 12 months prior to study enrollment, active infection, history of an allogeneic or autologous stem cell transplantation within 12 weeks, prior BCMA-directed bispecific antibody therapy, prior bispecific T-cell engaging therapy, or prior BCMA CAR-T cell therapy.Patients received step-up dose of mg on Day 1, 25 mg on Day 8, and the first treatment dose of 200 mg on Day 15 of LYNOZYFIC by intravenous infusion. Then, patients received 200 mg of LYNOZYFIC weekly from Week to Week 13, followed by 200 mg every other week thereafter. After at least 24 weeks, the Phase patients who achieved very good partial response (VGPR) or greater received 200 mg of LYNOZYFIC every weeks. Patients were treated until disease progression or unacceptable toxicity.The efficacy population included 80 patients who had received at least four prior lines of therapy. The median age was 71 (range: 37 to 83) years with 30% of patients 75 years or older; 64% were male and 36% were female; 69% were White, 14% were Black or African American, 13% were Asian, and 2.5% were Hispanic/Latino.The International Staging System (ISS) at study entry was Stage in 39%, Stage II in 36%, and Stage III in 19%. High-risk cytogenetics (presence of del(17p), t(4;14) and t(14;16)) were present in 40% of patients. Eighteen percent of patients had extramedullary disease at baseline.The median number of prior lines of therapy was (range: to 13); 83% of patients were refractory to the last line of therapy. Sixty-five percent of patients received prior stem cell transplantation. Seventy-nine percent of patients were triple-class refractory (refractory to proteasome inhibitor, an immunomodulatory agent, and an anti-CD38 monoclonal antibody). Thirteen percent of patients were previously treated with BCMA antibody-drug conjugate.Efficacy was established based on objective response rate (ORR) as determined by blinded independent review committee (IRC), as measured using the International Myeloma Working Group (IMWG) criteria (see Table 10). The median time to first response was 0.95 months (range: 0.5 to months). With median follow-up of 11.3 months among responders, the estimated duration of response (DOR) rate was 89% (95% CI: 77, 95) at months and 72% (95% CI: 54, 84) at 12 months.Table 10:Efficacy Results for LINKER-MM1Efficacy EndpointsLYNOZYFIC N=80CI=confidence interval; NE=not estimableObjective Response Rate (ORR) (n)70% (56)(95% CI)(59,80) Complete response (CR) or better, (n)45% (36) (95% CI)(34,57) Stringent complete response (sCR), (n)39% (31) Complete response (CR), (n)6% (5) Very good partial response (VGPR) (n)19% (15) Partial response (PR), (n)6% (5)Duration of Response (DOR)Based on Kaplan-Meier estimation. Median, months (95% CI)NR (12, NE).

CLINICAL TRIALS EXPERIENCE SECTION.

6.1 Clinical Trials Experience. Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice.. Relapsed or Refractory Multiple MyelomaThe safety of LYNOZYFIC was evaluated in LINKER-MM1 [see Clinical Studies (14)]. Patients (n=117) received LYNOZYFIC as step-up doses of mg on Day and 25 mg on Day 8, and the first treatment dose of 200 mg on Day 15. Patients then received 200 mg intravenously once weekly from Week to Week 13, followed by 200 mg every weeks from Week 14. In the Phase portion of the study, patients who achieved and maintained VGPR or better at or after Week 24 and received at least 17 doses of 200 mg were able to receive every 4-week dosing. The median duration of treatment was 47 weeks (range 1, 151); 55% of patients were exposed for months or longer and 36% were exposed for year or longer.The median age of patients who received LYNOZYFIC was 70 years (range: 37 to 91 years); 55% were male; 71% were White, 17% were Black or African American, and 9% were Asian.Serious adverse reactions occurred in 74% of patients who received LYNOZYFIC. Serious adverse reactions that occurred in >5% of patients included cytokine release syndrome (27%), pneumonia (13%), COVID-19 (7%), and acute kidney injury (5%). Fatal adverse reactions occurred in 7% of patients, and included sepsis (3.4%), chronic kidney disease (0.9%), pneumonia (0.9%), tumor lysis syndrome (0.9%), and encephalopathy (0.9%).Permanent discontinuation of LYNOZYFIC due to adverse reactions occurred in 16% of patients. Adverse reactions leading to discontinuation that occurred in at least patients included sepsis, pneumonia, and encephalopathy.Dosage interruptions or delays of LYNOZYFIC due to adverse reactions occurred in 74% of patients. Adverse reactions which required dosage interruption or delay in >10% of patients included neutropenia (29%), upper respiratory tract infection (18%), pneumonia (15%), and COVID-19 infection (11%).The most common adverse reactions (>=20%) were musculoskeletal pain, cytokine release syndrome, cough, upper respiratory tract infection, diarrhea, fatigue, pneumonia, nausea, headache, and dyspnea. The most common Grade to laboratory abnormalities (>=30%) were decreased lymphocyte count, decreased neutrophil count, decreased hemoglobin, and decreased white blood cell count.Table summarizes the adverse reactions in LINKER-MM1.Table 7:Adverse Reactions (>=10%) in Patients with Relapsed or Refractory Multiple Myeloma Who Received LYNOZYFIC in LINKER-MM1Adverse ReactionLYNOZYFIC (N=117)All Grades (%)Grade or (%)Musculoskeletal and connective tissue disorders Musculoskeletal painIncludes other related terms. 533.4Only Grade adverse reactions occurred. Immune system disorders Cytokine release syndrome460.9 Hypogammaglobulinemia130.9 Respiratory, thoracic and mediastinal disorders Cough 390 Dyspnea 210.9 Nasal congestion160Infections and infestations Upper respiratory tract infection 356 PneumoniaPneumonia includes atypical pneumonia, COVID-19 pneumonia, PJP, pneumonia, pneumonia cytomegaloviral, pneumonia fungal, pneumonia influenzal, and pneumonia viral. Includes fatal outcome. 2821 COVID-19175 Urinary tract infections 168 Sepsis106Gastrointestinal disorders Diarrhea351.7 Nausea230 Vomiting190 Constipation170General disorders and administration site conditions Fatigue 340 Edema 190.9 Pyrexia170Nervous system disorders Headache 220.9 Encephalopathy Encephalopathy includes agitation, amnesia, cognitive disorder, confusional state, delirium, depressed level of consciousness, encephalopathy (including hyperammonemic and toxic encephalopathy), irritability, lethargy, memory impairment, mental status changes, somnolence, and excludes ICANS. 183.4 Sensory Neuropathy 130.9Metabolism and nutrition disorders Decreased appetite150.9 Skin and subcutaneous tissue disorders RashRash includes dermatitis acneiform, dermatitis contact, drug eruption, erythema, rash, rash erythematous, rash maculo-papular, rash pruritic, and stasis dermatitis. 151.7 Psychiatric disorders Insomnia130Vascular disorders Hypertension104.3 Clinically significant adverse reactions that occurred in <10% of patients treated with LYNOZYFIC included IRR, motor dysfunction, febrile neutropenia, ICANS, CMV infection, and PML.Table summarizes the laboratory abnormalities in LINKER-MM1.Table 8:Select Laboratory Abnormalities (>=5% for Grade or 4) That Worsened from Baseline in Patients with Multiple Myeloma Treated with LYNOZYFIC in LINKER-MM1Laboratory AbnormalityLaboratory tests were graded according to NCI-CTCAE (National Cancer Institute Common Terminology Criteria for Adverse Events) Version 5.0. LYNOZYFIC (N=117)The denominator used to calculate the rate varied from 106 to 117 based on the number of patients with baseline value and at least one post-treatment value. All Grades (%)Grades or (%)Hematology Lymphocyte count decreased9792 Hemoglobin decreased7242 Platelet count decreased6419 White blood cell count decreased6331 Neutrophil count decreased6247Chemistry Aspartate aminotransferase increased6110 Phosphorus decreased5524 Creatinine increased477 Alanine aminotransferase increased466.

CONTRAINDICATIONS SECTION.

4 CONTRAINDICATIONS. None.. None. (4).

DESCRIPTION SECTION.

11 DESCRIPTION. Linvoseltamab-gcpt, bispecific B-cell maturation antigen (BCMA)-directed CD3 T-cell engager, is recombinant human immunoglobulin (Ig)G4 antibody. Linvoseltamab-gcpt is produced by recombinant DNA technology in Chinese hamster ovary (CHO) cell suspension culture. The molecular weight of linvoseltamab-gcpt is approximately 146 kDa.LYNOZYFIC (linvoseltamab-gcpt) injection for intravenous use is sterile, preservative-free, clear to slightly opalescent, colorless to pale yellow solution with pH 6.0.Each LYNOZYFIC mg/2.5 mL vial contains mg of linvoseltamab-gcpt. Each mL contains mg of linvoseltamab-gcpt, histidine (0.7 mg), L-histidine hydrochloride monohydrate (1.1 mg), polysorbate 80 (1 mg), sucrose (100 mg), and Water for Injection, USP.Each LYNOZYFIC 200 mg/10 mL vial contains 200 mg of linvoseltamab-gcpt. Each mL contains 20 mg of linvoseltamab-gcpt, histidine (0.7 mg), L-histidine hydrochloride monohydrate (1.1 mg), polysorbate 80 (1 mg), sucrose (100 mg), and Water for Injection, USP.

DOSAGE FORMS & STRENGTHS SECTION.

3 DOSAGE FORMS AND STRENGTHS. LYNOZYFIC is clear to slightly opalescent, colorless to pale yellow solution, available as:Injection: mg/2.5 mL (2 mg/mL) single-dose vialInjection: 200 mg/10 mL (20 mg/mL) single-dose vial. Injection: mg/2.5 mL (2 mg/mL) single-dose vial. Injection: 200 mg/10 mL (20 mg/mL) single-dose vial. Injection:5 mg/2.5 mL (2 mg/mL) single-dose vial (3)200 mg/10 mL (20 mg/mL) single-dose vial (3). mg/2.5 mL (2 mg/mL) single-dose vial (3). 200 mg/10 mL (20 mg/mL) single-dose vial (3).

DRUG INTERACTIONS SECTION.

7 DRUG INTERACTIONS. 7.1Effects of LYNOZYFIC on Other Drugs. Certain CYP substratesMonitor for toxicity unless otherwise recommended in the Prescribing Information of certain CYP substrates where minimal changes in the concentration may lead to serious adverse reactions when used concomitantly with LYNOZYFIC.Linvoseltamab-gcpt causes the release of cytokines [see Clinical Pharmacology (12.2)] that may suppress cytochrome P450 (CYP) enzyme activity. Concomitant use with LYNOZYFIC increases CYP substrate exposure which may increase the risk of adverse reactions related to these substrates. Increased CYP substrate exposure is more likely to occur from initiation of the LYNOZYFIC step-up dosing schedule up to 14 days after the first 200 mg dose, and during and after CRS [see Warnings and Precautions (5.1)].

FEMALES & MALES OF REPRODUCTIVE POTENTIAL SECTION.

8.3 Females and Males of Reproductive Potential. LYNOZYFIC may cause fetal harm when administered to pregnant woman [see Use in Specific Populations (8.1)].. Pregnancy TestingVerify the pregnancy status of females of reproductive potential prior to initiating treatment with LYNOZYFIC.. Contraception. FemalesAdvise females of reproductive potential to use effective contraception during treatment and for months after the last dose of LYNOZYFIC.

GERIATRIC USE SECTION.

8.5 Geriatric Use. Of the 117 patients with relapsed or refractory multiple myeloma who received LYNOZYFIC, 42 (36%) of patients were 65 to 74 years of age and 31 (26%) were 75 years of age and older [see Clinical Studies (14)]. No overall differences in safety or effectiveness were observed in patients 65 years of age and older, including patients 75 years of age and older, when compared with younger patients.

HOW SUPPLIED SECTION.

16 HOW SUPPLIED/STORAGE AND HANDLING. LYNOZYFIC (linvoseltamab-gcpt) injection is clear to slightly opalescent, colorless to pale yellow solution in single-dose vial. It is supplied as provided in Table 11.Table 11:Packaging ConfigurationsCarton contentsNDCOne mg/2.5 mL (2 mg/mL) single-dose vial61755-054-01One 200 mg/10 mL (20 mg/mL) single-dose vial61755-056-01. Store unopened vial in refrigerator at 2C to 8C (36F to 46F) in the original carton to protect from light. Do not freeze or shake.

IMMUNOGENICITY.

12.6Immunogenicity. The observed incidence of anti-drug antibodies is highly dependent on the sensitivity and specificity of the assay. Differences in assay methods preclude meaningful comparisons of the incidence of anti-drug antibodies in the study described below with the incidence of anti-drug antibodies in other studies, including those of linvoseltamab-gcpt.During treatment in LINKER-MM1 (evaluated through 30 months) [see Clinical Studies (14)], 1% (2/192) of LYNOZYFIC-treated patients developed anti-linvoseltamab-gcpt antibodies. Because of the low occurrence of anti-drug antibodies, the effect of these antibodies on the pharmacokinetics, pharmacodynamics, safety, and/or effectiveness of linvoseltamab products is unknown.

INDICATIONS & USAGE SECTION.

1 INDICATIONS AND USAGE. LYNOZYFIC is indicated for the treatment of adult patients with relapsed or refractory multiple myeloma who have received at least four prior lines of therapy, including proteasome inhibitor, an immunomodulatory agent, and an anti-CD38 monoclonal antibody.This indication is approved under accelerated approval based on response rate and durability of response [see Clinical Studies (14)]. Continued approval for this indication may be contingent upon verification and description of clinical benefit in confirmatory trial(s).. LYNOZYFIC is bispecific B-cell maturation antigen (BCMA)-directed CD3 T-cell engager indicated for the treatment of adult patients with relapsed or refractory multiple myeloma who have received at least four prior lines of therapy, including proteasome inhibitor, an immunomodulatory agent, and an anti-CD38 monoclonal antibody.This indication is approved under accelerated approval based on response rate and durability of response. Continued approval for this indication may be contingent upon verification and description of clinical benefit in confirmatory trial(s). (1).

INFORMATION FOR PATIENTS SECTION.

17 PATIENT COUNSELING INFORMATION. Advise the patient to read the FDA-approved patient labeling (Medication Guide).. Cytokine Release Syndrome (CRS)Advise patients that they should be hospitalized for 24 hours after administration of the first and second step-up doses of LYNOZYFIC [see Dosage and Administration (2.2)]. Inform patients of the risk of CRS, and discuss the signs and symptoms associated with CRS, including fever, chills, hypoxia, tachycardia, and hypotension. Counsel patients to seek immediate medical attention should signs or symptoms of CRS occur at any time [see Warnings and Precautions (5.1)].. Neurologic Toxicity, including Immune Effector Cell-Associated Neurotoxicity SyndromeDiscuss the signs and symptoms associated with neurologic toxicity, including ICANS, including confusion, depressed level of consciousness, and lethargy. Advise patients to immediately contact their healthcare provider if they experience any signs or symptoms of neurologic toxicity. Advise patients to refrain from driving, or operating heavy or potentially dangerous machinery, for 48 hours after completion of each of the step-up doses or if they experience new onset of neurologic toxicity symptoms until the symptoms resolve [see Warnings and Precautions (5.2)]. LYNOZYFIC REMSLYNOZYFIC is available only through restricted program called the LYNOZYFIC REMS. Inform patients that they will be given Patient Wallet Card that they should carry with them at all times and show to all of their healthcare providers. This card describes symptoms of CRS and neurologic toxicity, including ICANS which, if experienced, should prompt the patient to seek immediate medical attention [see Warnings and Precautions (5.3)].. InfectionsAdvise patients of the risk of serious infections. Instruct patients to immediately report infection-related signs or symptoms of infection (e.g., fever, chills, weakness) [see Warnings and Precautions (5.4)].. NeutropeniaDiscuss the signs and symptoms associated with neutropenia and febrile neutropenia [see Warnings and Precautions (5.5)].. HepatotoxicityAdvise patients that liver enzymes elevations may occur and that they should report symptoms that may indicate liver toxicity, including fatigue, anorexia, right upper abdominal discomfort, dark urine, or jaundice [see Warnings and Precautions (5.6)]. Embryo-Fetal ToxicityAdvise pregnant women and females of reproductive potential of the potential risk to fetus. Advise females of reproductive potential to inform their healthcare provider if they are pregnant or become pregnant. Advise females of reproductive potential to use effective contraception during treatment with LYNOZYFIC and for months after the last dose [see Warnings and Precautions (5.7), Use in Specific Populations (8.1, 8.3)].. LactationAdvise women not to breastfeed during treatment with LYNOZYFIC and for months after the last dose [see Use in Specific Populations (8.2)].

LACTATION SECTION.

8.2 Lactation. Risk SummaryThere are no data on the presence of linvoseltamab-gcpt in human milk, the effects on the breastfed child, or the effects on milk production. Maternal IgG is known to be present in human milk.Because of the potential for serious adverse reactions in breastfed child, advise women not to breastfeed during treatment with LYNOZYFIC and for months after the last dose.

MECHANISM OF ACTION SECTION.

12.1Mechanism of Action. Linvoseltamab-gcpt is bispecific T-cell engaging antibody that binds to the CD3 receptor expressed on the surface of T-cells and B-cell maturation antigen (BCMA) expressed on the surface of multiple myeloma cells and some healthy B-lineage cells.In vitro, linvoseltamab-gcpt activated T-cells, caused the release of various proinflammatory cytokines, and resulted in the lysis of multiple myeloma cells. Linvoseltamab-gcpt had anti-tumor activity in mouse models of multiple myeloma.

NONCLINICAL TOXICOLOGY SECTION.

13 NONCLINICAL TOXICOLOGY. 13.1Carcinogenesis, Mutagenesis, Impairment of Fertility. No carcinogenicity or genotoxicity studies have been conducted with linvoseltamab-gcpt.No animal studies have been performed to evaluate the effects of linvoseltamab-gcpt on fertility.

PHARMACODYNAMICS SECTION.

12.2 Pharmacodynamics. The 200 mg once weekly dosing regimen was associated with better objective response rate and complete response rate when compared to the 50 mg once weekly (0.25 times the recommended dosage) dosing regimen in patients with relapsed or refractory multiple myeloma.Linvoseltamab-gcpt exposure-response relationships have not been fully characterized.. Effect on Circulating CytokinesTransient elevation of circulating cytokines (IL-2, IL-6, and IFN-) was primarily observed during the step-up dose regimen and the first full 200 mg dose. The highest elevation of cytokines was generally observed hours after each infusion and generally returned to baseline prior to the next dose. Limited cytokine release was observed following subsequent doses.

PHARMACOKINETICS SECTION.

12.3 Pharmacokinetics. Pharmacokinetic (PK) parameters were evaluated at the recommended dosage in patients with relapsed or refractory multiple myeloma and are presented as geometric mean (CV%) unless otherwise specified.Linvoseltamab-gcpt PK exposures following use of the recommended dosing schedule are presented in Table 9. Linvoseltamab-gcpt Ctrough increased more than proportionally over dose range of 96 mg to 800 mg (0.48 to times the recommended full dose). Linvoseltamab-gcpt maximum concentration (127 mg/L [51%]) is achieved after the first dose of the every-2-weeks dosing regimen (i.e., the 12th dose of 200 mg).Table 9:Geometric Mean (CV%) Exposure Following the Recommended Dosage for Linvoseltamab-gcptDosing PeriodCmax (mg/L)Ctrough (mg/L)Cavg (mg /L)First 200 mg weekly dose52.7 (37.2)15.5 (64.8)27.4 (34.2)End of 200 mg weekly dosing (11th dose of 200 mg)124 (50.4)61.8 (123)84.6 (74.6)End of 200 mg every weeks dosing (16th dose of 200 mg)97.9 (52.7)30.2 (213)51.9 (95.3)Steady stateSteady state values are approximated at Week 28. with 200 mg every weeks dosing64.8 (45.1)6.3 (362)20.5 (84.6). DistributionLinvoseltamab-gcpt volume of distribution (Vd) is 7.05 (33.6%).. EliminationLinvoseltamab-gcpt clearance is 0.68 L/day (52.2%) at baseline and 0.43 L/day (83.8%) at steady state.Linvoseltamab-gcpt clearance decreases over time because its elimination is mediated by two parallel processes: linear, non-saturable catabolic process and nonlinear, saturable target-mediated pathway. Patients who discontinue linvoseltamab-gcpt are expected to have 97% reduction from Cmax at median (5th to 95th percentile) time of 77.7 (18 to 154) days after last dose.. MetabolismLinvoseltamab-gcpt is expected to be metabolized into small peptides by catabolic pathways.. Specific PopulationsNo clinically significant differences in the pharmacokinetics of linvoseltamab-gcpt were observed based on age (37 to 91 years), weight (44 to 172 kg), sex, race (White, Asian, or Black), ethnicity (Hispanic/Latino or not Hispanic/Latino), mild to moderate renal impairment (creatinine clearance [CrCL] 30 to 89 mL/min, by Cockcroft-Gault [C-G] equation), or mild hepatic impairment (total bilirubin less than or equal to upper limit of normal [ULN] with AST greater than ULN or total bilirubin greater than to 1.5 times ULN with any AST).The effect of severe renal impairment (CrCL 15 to 29 mL/min), end-stage renal disease (CrCL less than 15 mL/min), and moderate to severe hepatic impairment (total bilirubin greater than 1.5 times ULN with any AST) on the pharmacokinetics of linvoseltamab-gcpt is unknown.

PREGNANCY SECTION.

8.1 Pregnancy. Risk SummaryBased on the mechanism of action, LYNOZYFIC may cause fetal harm when administered to pregnant woman [see Clinical Pharmacology (12.1)]. There are no available data on the use of LYNOZYFIC in pregnant women to evaluate for drug associated risk. No animal reproductive or developmental toxicity studies have been conducted with LYNOZYFIC.Linvoseltamab-gcpt causes T-cell activation and cytokine release; immune activation may compromise pregnancy maintenance. In addition, based on the finding of B-cell depletion in non-pregnant animals, linvoseltamab-gcpt can cause B-cell lymphocytopenia in infants exposed to linvoseltamab-gcpt in-utero. Human immunoglobulin (IgG) is known to cross the placenta after the first trimester of pregnancy; therefore, linvoseltamab-gcpt has the potential to be transmitted from the mother to the developing fetus. Advise women of the potential risk to the fetus.LYNOZYFIC is associated with hypogammaglobulinemia, therefore, assessment of immunoglobulin levels in newborns of mothers treated with LYNOZYFIC should be considered.In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2% to 4% and 15% to 20%, respectively.

SPL MEDGUIDE SECTION.

MEDICATION GUIDELYNOZYFIC(TM) (lin-oh-ZI-fik)(linvoseltamab-gcpt)injection, for intravenous useThis Medication Guide has been approved by the U.S. Food and Drug Administration.Issued: July 2025 What is the most important information should know about LYNOZYFICLYNOZYFIC may cause serious or life-threatening side effects, including:Cytokine Release Syndrome (CRS) and infusion related reactions (IRR). CRS is common during treatment with LYNOZYFIC and can also be serious or life-threatening. Tell your healthcare provider or get medical help right away if you develop any signs or symptoms of CRS or IRR, including:fever of 100.4F (38C) or higherchills or shakingtrouble breathingfast heartbeatdizziness or light-headednessNeurologic problems. LYNOZYFIC can cause neurologic problems that can be serious or life-threatening. Tell your healthcare provider or get medical help right away if you develop any signs or symptoms of neurologic problems, including:headacheagitation, trouble staying awake, confusion or disorientation, seeing or hearing things that are not real (hallucinations)trouble speaking, writing, thinking, remembering things, paying attention, or understanding thingsproblems walking, muscle weakness, shaking (tremors), loss of balance, or muscle spasmsnumbness and tingling (feeling like pins and needles)burning, throbbing, or stabbing painchanges in your handwritingseizuresDue to the risk of CRS and neurologic problems, you will receive LYNOZYFIC on step-up dosing schedule and should be hospitalized for 24 hours after the first and second step-up doses. During the step-up dosing schedule:For your first dose, you will receive smaller step-up dose of LYNOZYFIC on Day of your treatment.For your second dose, you will receive larger step-up dose of LYNOZYFIC, which is usually given on Day of your treatment.For your third dose, you will receive the first treatment dose of LYNOZYFIC, which is usually given on Day 15 of your treatment. Your healthcare provider may repeat one or both of the step-up doses depending on side effects or if your treatment is delayed.Before the step-up doses and the first two treatment doses of LYNOZYFIC, you will receive medicines to help reduce your risk of CRS and IRR. Your healthcare provider will decide if you need to receive medicine to help reduce your risk of side effects with future doses.See How will receive LYNOZYFIC for more information about how you will receive LYNOZYFIC.LYNOZYFIC is available only through the LYNOZYFIC Risk Evaluation and Mitigation Strategy (REMS) due to the risk of side effects of CRS and neurologic problems. You will receive Patient Wallet Card from your healthcare provider. Carry the LYNOZYFIC Patient Wallet Card with you at all times and show it to all of your healthcare providers. The LYNOZYFIC Patient Wallet Card lists signs and symptoms of CRS and neurologic problems. Get medical help right away if you develop any of the signs and symptoms listed on the LYNOZYFIC Patient Wallet Card. You may need to be treated in hospital.Your healthcare provider will monitor you for signs and symptoms of CRS and neurologic problems during treatment with LYNOZYFIC, as well as other side effects, and may treat you in hospital if needed. Your healthcare provider may temporarily stop or completely stop your treatment with LYNOZYFIC if you develop CRS, neurologic problems, or any other severe side effects.If you have any questions about LYNOZYFIC, ask your healthcare provider.See What are the possible side effects of LYNOZYFIC below for more information about side effects.What is LYNOZYFICLYNOZYFIC is prescription medicine used to treat adults with multiple myeloma who: have already received at least treatment regimens, including proteasome inhibitor, an immunomodulatory agent and an anti-CD38 monoclonal antibody to treat their multiple myeloma, and their cancer has come back or did not respond to prior treatment.It is not known if LYNOZYFIC is safe and effective in children.Before receiving LYNOZYFIC, tell your healthcare provider about all of your medical conditions, including if you:have an infection.are pregnant or plan to become pregnant. LYNOZYFIC may harm your unborn baby. Tell your healthcare provider right away if you become pregnant or think that you may be pregnant during treatment with LYNOZYFIC. Females who are able to become pregnant: Your healthcare provider should do pregnancy test before you start treatment with LYNOZYFIC.You should use an effective form of birth control (contraception) during treatment with LYNOZYFIC and for months after your last dose of LYNOZYFIC. are breastfeeding or plan to breastfeed. It is not known whether LYNOZYFIC passes into your breast milk. Do not breastfeed during treatment with LYNOZYFIC and for months after your last dose of LYNOZYFIC.Tell your healthcare provider about all the medicines you take, including prescription and over-the-counter medicines, vitamins, and herbal supplements. How will receive LYNOZYFICLYNOZYFIC will be given to you by your healthcare provider by infusion through needle placed in vein (intravenous infusion).See What is the most important information should know about LYNOZYFIC for more information about how you will receive LYNOZYFIC. After the step-up dosing schedule, the treatment dose of LYNOZYFIC is usually given time each week for 11 doses, and then time every other week for doses. After these doses and based on how your disease responds, your healthcare provider will decide if you are able to receive LYNOZYFIC less often (every weeks) or will continue to have every other week treatment.Your healthcare provider will decide how long you will receive treatment with LYNOZYFIC.If you miss any appointments, call your healthcare provider as soon as possible to reschedule your appointment. It is important for you to be monitored closely for side effects during treatment with LYNOZYFIC.What should avoid while receiving LYNOZYFICDo not drive, or operate heavy or potentially dangerous machinery, or do other dangerous activities for 48 hours after completing each of your step-up doses or at any time during treatment with LYNOZYFIC if you develop new neurologic symptoms, until the symptoms go away.See What is the most important information should know about LYNOZYFIC for more information about signs and symptoms of neurologic problems.What are the possible side effects of LYNOZYFICLYNOZYFIC may cause serious side effects, including:See What is the most important information should know about LYNOZYFIC Infections. LYNOZYFIC can cause bacterial, viral, or fungal infections that are serious, life-threatening, or that may lead to death. Upper respiratory tract infections and pneumonia are common during treatment with LYNOZYFIC.Your healthcare provider will monitor you for signs and symptoms of infection before and during treatment with LYNOZYFIC.Your healthcare provider may prescribe medicines for you to help prevent infections and treat you as needed if you develop an infection during treatment with LYNOZYFIC.Tell your healthcare provider right away if you develop any signs or symptoms of infection during treatment with LYNOZYFIC, including: fever of 100.4 (38 C) or higherchillscoughshortness of breath chest painsore throatpain during urinationfeeling weak or generally unwellDecreased white blood cell counts. Decreased white blood cell counts are common during treatment with LYNOZYFIC and can also be severe. Fever can happen with low white blood cell counts and may be sign that you have an infection. Your healthcare provider will check your blood cell counts before you start treatment and during treatment with LYNOZYFIC, and will treat you as needed.Liver problems. LYNOZYFIC can cause increased liver enzymes and bilirubin in your blood. These increases can happen with or without you also having CRS. Your healthcare provider will do blood tests to check your liver before starting and during treatment with LYNOZYFIC. Tell your healthcare provider if you develop any of the following signs or symptoms of liver problems:tirednessloss of appetitepain in your right upper stomach-area (abdomen)dark urineyellowing of your skin or the white part of your eyesThe most common side effects of LYNOZYFIC include: muscle and bone paincoughdiarrheatiredness or weaknessnauseaheadacheshortness of breathThe most common severe abnormal blood test results with LYNOZYFIC include: low white blood cell counts and low red blood cell counts.These are not all of the possible side effects of LYNOZYFIC.Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088.General information about safe and effective use of LYNOZYFICMedicines are sometimes prescribed for purposes other than those listed in Medication Guide. You can ask your pharmacist or healthcare provider for information about LYNOZYFIC that is written for health professionals.What are the ingredients in LYNOZYFICActive ingredient: linvoseltamab-gcpt Inactive ingredients: histidine, L-histidine hydrochloride monohydrate, polysorbate 80, sucrose, and Water for Injection. Manufactured by: Regeneron Pharmaceuticals, Inc., Tarrytown, NY 10591 U.S. License No. 1760For more information about LYNOZYFIC, go to www.LYNOZYFIC.com or call 1-844-746-4363.LYNOZYFIC is trademark of Regeneron Pharmaceuticals, Inc.(C) 2025 Regeneron Pharmaceuticals, Inc.All rights reserved.. Cytokine Release Syndrome (CRS) and infusion related reactions (IRR). CRS is common during treatment with LYNOZYFIC and can also be serious or life-threatening. Tell your healthcare provider or get medical help right away if you develop any signs or symptoms of CRS or IRR, including:. fever of 100.4F (38C) or higher. chills or shaking. trouble breathing. fast heartbeat. dizziness or light-headedness. Neurologic problems. LYNOZYFIC can cause neurologic problems that can be serious or life-threatening. Tell your healthcare provider or get medical help right away if you develop any signs or symptoms of neurologic problems, including:. headache. agitation, trouble staying awake, confusion or disorientation, seeing or hearing things that are not real (hallucinations). trouble speaking, writing, thinking, remembering things, paying attention, or understanding things. problems walking, muscle weakness, shaking (tremors), loss of balance, or muscle spasms. numbness and tingling (feeling like pins and needles). burning, throbbing, or stabbing pain. changes in your handwriting. seizures. During the step-up dosing schedule:For your first dose, you will receive smaller step-up dose of LYNOZYFIC on Day of your treatment.For your second dose, you will receive larger step-up dose of LYNOZYFIC, which is usually given on Day of your treatment.For your third dose, you will receive the first treatment dose of LYNOZYFIC, which is usually given on Day 15 of your treatment. For your first dose, you will receive smaller step-up dose of LYNOZYFIC on Day of your treatment.. For your second dose, you will receive larger step-up dose of LYNOZYFIC, which is usually given on Day of your treatment.. For your third dose, you will receive the first treatment dose of LYNOZYFIC, which is usually given on Day 15 of your treatment. Your healthcare provider may repeat one or both of the step-up doses depending on side effects or if your treatment is delayed.. Before the step-up doses and the first two treatment doses of LYNOZYFIC, you will receive medicines to help reduce your risk of CRS and IRR. Your healthcare provider will decide if you need to receive medicine to help reduce your risk of side effects with future doses.. See How will receive LYNOZYFIC for more information about how you will receive LYNOZYFIC.. LYNOZYFIC is available only through the LYNOZYFIC Risk Evaluation and Mitigation Strategy (REMS) due to the risk of side effects of CRS and neurologic problems. You will receive Patient Wallet Card from your healthcare provider. Carry the LYNOZYFIC Patient Wallet Card with you at all times and show it to all of your healthcare providers. The LYNOZYFIC Patient Wallet Card lists signs and symptoms of CRS and neurologic problems. Get medical help right away if you develop any of the signs and symptoms listed on the LYNOZYFIC Patient Wallet Card. You may need to be treated in hospital.. have already received at least treatment regimens, including proteasome inhibitor, an immunomodulatory agent and an anti-CD38 monoclonal antibody to treat their multiple myeloma, and their cancer has come back or did not respond to prior treatment.. have an infection.. are pregnant or plan to become pregnant. LYNOZYFIC may harm your unborn baby. Tell your healthcare provider right away if you become pregnant or think that you may be pregnant during treatment with LYNOZYFIC. Females who are able to become pregnant: Your healthcare provider should do pregnancy test before you start treatment with LYNOZYFIC.You should use an effective form of birth control (contraception) during treatment with LYNOZYFIC and for months after your last dose of LYNOZYFIC. Your healthcare provider should do pregnancy test before you start treatment with LYNOZYFIC.. You should use an effective form of birth control (contraception) during treatment with LYNOZYFIC and for months after your last dose of LYNOZYFIC.. are breastfeeding or plan to breastfeed. It is not known whether LYNOZYFIC passes into your breast milk. Do not breastfeed during treatment with LYNOZYFIC and for months after your last dose of LYNOZYFIC.. LYNOZYFIC will be given to you by your healthcare provider by infusion through needle placed in vein (intravenous infusion).. See What is the most important information should know about LYNOZYFIC for more information about how you will receive LYNOZYFIC. After the step-up dosing schedule, the treatment dose of LYNOZYFIC is usually given time each week for 11 doses, and then time every other week for doses. After these doses and based on how your disease responds, your healthcare provider will decide if you are able to receive LYNOZYFIC less often (every weeks) or will continue to have every other week treatment.. Your healthcare provider will decide how long you will receive treatment with LYNOZYFIC.. If you miss any appointments, call your healthcare provider as soon as possible to reschedule your appointment. It is important for you to be monitored closely for side effects during treatment with LYNOZYFIC.. See What is the most important information should know about LYNOZYFIC Infections. LYNOZYFIC can cause bacterial, viral, or fungal infections that are serious, life-threatening, or that may lead to death. Upper respiratory tract infections and pneumonia are common during treatment with LYNOZYFIC.Your healthcare provider will monitor you for signs and symptoms of infection before and during treatment with LYNOZYFIC.Your healthcare provider may prescribe medicines for you to help prevent infections and treat you as needed if you develop an infection during treatment with LYNOZYFIC.Tell your healthcare provider right away if you develop any signs or symptoms of infection during treatment with LYNOZYFIC, including: Your healthcare provider will monitor you for signs and symptoms of infection before and during treatment with LYNOZYFIC.. Your healthcare provider may prescribe medicines for you to help prevent infections and treat you as needed if you develop an infection during treatment with LYNOZYFIC.. Tell your healthcare provider right away if you develop any signs or symptoms of infection during treatment with LYNOZYFIC, including:. fever of 100.4 (38 C) or higherchillscoughshortness of breath. fever of 100.4 (38 C) or higher. chills. cough. shortness of breath. chest painsore throatpain during urinationfeeling weak or generally unwell. chest pain. sore throat. pain during urination. feeling weak or generally unwell. Decreased white blood cell counts. Decreased white blood cell counts are common during treatment with LYNOZYFIC and can also be severe. Fever can happen with low white blood cell counts and may be sign that you have an infection. Your healthcare provider will check your blood cell counts before you start treatment and during treatment with LYNOZYFIC, and will treat you as needed.. Liver problems. LYNOZYFIC can cause increased liver enzymes and bilirubin in your blood. These increases can happen with or without you also having CRS. Your healthcare provider will do blood tests to check your liver before starting and during treatment with LYNOZYFIC. Tell your healthcare provider if you develop any of the following signs or symptoms of liver problems:. tiredness. loss of appetite. pain in your right upper stomach-area (abdomen). dark urine. yellowing of your skin or the white part of your eyes. muscle and bone pain. cough. diarrhea. tiredness or weakness. nausea. headache. shortness of breath.

SPL UNCLASSIFIED SECTION.

2.1Important Administration Instructions. Administer LYNOZYFIC intravenously according to the step-up schedule to reduce the incidence and severity of cytokine release syndrome (CRS) [see Dosage and Administration (2.2)].Administer only as an intravenous infusion after dilution in 0.9% Sodium Chloride Injection [see Dosage and Administration (2.6)].Administer pretreatment medications [see Dosage and Administration (2.3)].LYNOZYFIC should be administered by healthcare provider with immediate access to emergency equipment and appropriate medical support to manage severe reactions such as cytokine release syndrome (CRS), infusion-related reactions (IRR), and neurologic toxicity, including ICANS [see Warnings and Precautions (5.1 and 5.2)].Due to the risk of CRS and neurologic toxicity, including ICANS, patients should be hospitalized for 24 hours after administration of the first step-up dose, and for 24 hours after administration of the second step-up dose.. Administer LYNOZYFIC intravenously according to the step-up schedule to reduce the incidence and severity of cytokine release syndrome (CRS) [see Dosage and Administration (2.2)].. Administer only as an intravenous infusion after dilution in 0.9% Sodium Chloride Injection [see Dosage and Administration (2.6)].. Administer pretreatment medications [see Dosage and Administration (2.3)].. LYNOZYFIC should be administered by healthcare provider with immediate access to emergency equipment and appropriate medical support to manage severe reactions such as cytokine release syndrome (CRS), infusion-related reactions (IRR), and neurologic toxicity, including ICANS [see Warnings and Precautions (5.1 and 5.2)].. Due to the risk of CRS and neurologic toxicity, including ICANS, patients should be hospitalized for 24 hours after administration of the first step-up dose, and for 24 hours after administration of the second step-up dose.

STORAGE AND HANDLING SECTION.

Store unopened vial in refrigerator at 2C to 8C (36F to 46F) in the original carton to protect from light. Do not freeze or shake.

USE IN SPECIFIC POPULATIONS SECTION.

8 USE IN SPECIFIC POPULATIONS. Lactation: Advise not to breastfeed. (8.2). 8.1 Pregnancy. Risk SummaryBased on the mechanism of action, LYNOZYFIC may cause fetal harm when administered to pregnant woman [see Clinical Pharmacology (12.1)]. There are no available data on the use of LYNOZYFIC in pregnant women to evaluate for drug associated risk. No animal reproductive or developmental toxicity studies have been conducted with LYNOZYFIC.Linvoseltamab-gcpt causes T-cell activation and cytokine release; immune activation may compromise pregnancy maintenance. In addition, based on the finding of B-cell depletion in non-pregnant animals, linvoseltamab-gcpt can cause B-cell lymphocytopenia in infants exposed to linvoseltamab-gcpt in-utero. Human immunoglobulin (IgG) is known to cross the placenta after the first trimester of pregnancy; therefore, linvoseltamab-gcpt has the potential to be transmitted from the mother to the developing fetus. Advise women of the potential risk to the fetus.LYNOZYFIC is associated with hypogammaglobulinemia, therefore, assessment of immunoglobulin levels in newborns of mothers treated with LYNOZYFIC should be considered.In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2% to 4% and 15% to 20%, respectively.. 8.2 Lactation. Risk SummaryThere are no data on the presence of linvoseltamab-gcpt in human milk, the effects on the breastfed child, or the effects on milk production. Maternal IgG is known to be present in human milk.Because of the potential for serious adverse reactions in breastfed child, advise women not to breastfeed during treatment with LYNOZYFIC and for months after the last dose.. 8.3 Females and Males of Reproductive Potential. LYNOZYFIC may cause fetal harm when administered to pregnant woman [see Use in Specific Populations (8.1)].. Pregnancy TestingVerify the pregnancy status of females of reproductive potential prior to initiating treatment with LYNOZYFIC.. Contraception. FemalesAdvise females of reproductive potential to use effective contraception during treatment and for months after the last dose of LYNOZYFIC.. 8.4 Pediatric Use. The safety and effectiveness of LYNOZYFIC have not been established in pediatric patients.. 8.5 Geriatric Use. Of the 117 patients with relapsed or refractory multiple myeloma who received LYNOZYFIC, 42 (36%) of patients were 65 to 74 years of age and 31 (26%) were 75 years of age and older [see Clinical Studies (14)]. No overall differences in safety or effectiveness were observed in patients 65 years of age and older, including patients 75 years of age and older, when compared with younger patients.

WARNINGS AND PRECAUTIONS SECTION.

5 WARNINGS AND PRECAUTIONS. Infections: Can cause serious or fatal infections. Monitor patients for signs or symptoms of infection and treat accordingly. (5.4)Neutropenia: Monitor complete blood cell counts at baseline and periodically during treatment. (5.5)Hepatotoxicity: Can cause hepatotoxicity. Monitor liver enzymes and bilirubin at baseline and during treatment as clinically indicated. (5.6)Embryo-Fetal Toxicity: May cause fetal harm. Advise females of reproductive potential of the potential risk to the fetus and to use effective contraception. (5.7, 8.1, 8.3). Infections: Can cause serious or fatal infections. Monitor patients for signs or symptoms of infection and treat accordingly. (5.4). Neutropenia: Monitor complete blood cell counts at baseline and periodically during treatment. (5.5). Hepatotoxicity: Can cause hepatotoxicity. Monitor liver enzymes and bilirubin at baseline and during treatment as clinically indicated. (5.6). Embryo-Fetal Toxicity: May cause fetal harm. Advise females of reproductive potential of the potential risk to the fetus and to use effective contraception. (5.7, 8.1, 8.3). 5.1Cytokine Release Syndrome (CRS). LYNOZYFIC can cause cytokine release syndrome (CRS), which can be serious or life-threatening.In LINKER-MM1, CRS occurred in 46% (54/117) of patients who received LYNOZYFIC at the recommended dose, with Grade CRS occurring in 35% (41/117) of patients, Grade in 10% (12/117), and Grade in 0.9% (1/117) [see Adverse Reactions (6.1)]. Thirty-eight percent (45/117) of patients had CRS following step-up dose 1, including patient who experienced Grade CRS; 8% (9/117) had an initial CRS event following subsequent dose. Seventeen percent (19/113) of patients developed CRS after step-up dose 2, 10% (11/111) developed CRS after the first full 200 mg dose of LYNOZYFIC, and 3.6% (4/110) developed CRS after the second full dose. Recurrent CRS occurred in 20% (23/117) of patients. The median time to onset of CRS from the end of infusion was 11 (range: -1 to 184) hours after the most recent dose with median duration of 15 (range: to 76) hours.Clinical signs and symptoms of CRS included, but were not limited to pyrexia, chills, hypoxia, tachycardia, and hypotension.Administer pretreatment medications and initiate therapy according to LYNOZYFIC step-up dosing to reduce the incidence and severity of CRS [see Dosage and Administration (2.2) and Dosage and Administration (2.3)]. Monitor patients for signs and symptoms of CRS after infusion. Counsel patients to seek immediate medical attention should signs or symptoms of CRS occur.At the first sign of CRS, immediately evaluate patients for hospitalization, manage per current practice guidelines, and administer supportive care; withhold LYNOZYFIC until CRS resolves and modify the next dose or permanently discontinue LYNOZYFIC based on severity [see Dosage and Administration (2.5)]. Infusion Related ReactionsInfusion-related reactions (IRR) may be clinically indistinguishable from manifestations of CRS. In the patients who were treated with the recommended step-up dosing regimen and pretreatment medications [see Dosage and Administration (2.2) and Dosage and Administration (2.3)], the rate of IRR was 9% [11/117 including Grade IRR (4.3%) and Grade IRR (1.7%)]. For IRR, interrupt or slow the rate of infusion or permanently discontinue LYNOZYFIC based on severity of reaction [see Dosage and Administration (2.5)].LYNOZYFIC is available only through restricted program under REMS [see Warnings and Precautions (5.3)].. 5.2Neurologic Toxicity, including Immune Effector Cell-Associated Neurotoxicity Syndrome. LYNOZYFIC can cause serious or life-threatening neurologic toxicity, including immune effector cell-associated neurotoxicity syndrome (ICANS) [see Adverse Reactions (6.1)]. In LINKER-MM1, neurologic toxicity occurred in 54% of patients, with Grade or neurologic toxicity occurring in 8%, at the recommended dose [see Adverse Reactions (6.1)]. Neurologic toxicities included ICANS, depressed level of consciousness, encephalopathy, and toxic encephalopathy.ICANS occurred in 8% of patients who received LYNOZYFIC with the recommended dosing regimen, including Grade events in 2.6%. Most patients experienced ICANS following step-up dose (5%). Two patients (1.8%) experienced initial ICANS following step-up dose and one patient developed the first occurrence of ICANS following subsequent full dose of LYNOZYFIC. Recurrent ICANS occurred in one patient. The median time to onset of ICANS was (range: to 4) day after the most recent dose with median duration of (range: to 11) days. The onset of ICANS can be concurrent with CRS, following resolution of CRS, or in the absence of CRS.The most common clinical signs and symptoms of ICANS are confusion, depressed level of consciousness, and lethargy. Monitor patients for signs and symptoms of neurologic toxicity during treatment. At the first sign of neurologic toxicity, including ICANS, immediately evaluate the patient; provide supportive therapy and consider further management per current practice guidelines. Withhold LYNOZYFIC until ICANS resolves and modify the next dose or permanently discontinue LYNOZYFIC based on severity [see Dosage and Administration (2.5)]. Counsel patients to seek immediate medical attention should signs or symptoms of neurologic toxicity occur at any time.Due to the potential for neurologic toxicity, including ICANS, patients receiving LYNOZYFIC are at risk of confusion and depressed consciousness. Advise patients to refrain from driving, or operating heavy or potentially dangerous machinery, for 48 hours after completion of each of the step-up doses [see Dosage and Administration (2.2)] and in the event of new onset of any neurological symptoms, until symptoms resolve.LYNOZYFIC is available only through restricted program under REMS [see Warnings and Precautions (5.3)].. 5.3LYNOZYFIC REMS. LYNOZYFIC is available only through restricted program under REMS called the LYNOZYFIC REMS because of the risks of CRS and neurologic toxicity, including ICANS [see Warnings and Precautions (5.1, 5.2)].Notable requirements of the LYNOZYFIC REMS include the following:Prescribers must be certified with the program by enrolling and completing training.Prescribers must counsel patients receiving LYNOZYFIC about the risk of CRS and neurologic toxicity, including ICANS, and provide patients with LYNOZYFIC Patient Wallet Card.Pharmacies and healthcare settings that dispense LYNOZYFIC must be certified with the LYNOZYFIC REMS program and must verify prescribers are certified through the LYNOZYFIC REMS program.Wholesalers and distributors must only distribute LYNOZYFIC to certified pharmacies or healthcare settings.Further information about the LYNOZYFIC REMS program is available at lynozyficREMS.com or by telephone at 1-855-212-6391.. Prescribers must be certified with the program by enrolling and completing training.. Prescribers must counsel patients receiving LYNOZYFIC about the risk of CRS and neurologic toxicity, including ICANS, and provide patients with LYNOZYFIC Patient Wallet Card.. Pharmacies and healthcare settings that dispense LYNOZYFIC must be certified with the LYNOZYFIC REMS program and must verify prescribers are certified through the LYNOZYFIC REMS program.. Wholesalers and distributors must only distribute LYNOZYFIC to certified pharmacies or healthcare settings.. 5.4Infections. LYNOZYFIC can cause serious, life-threatening, or fatal infections. In patients who received LYNOZYFIC at the recommended dose in LINKER-MM1, serious infections, including opportunistic infections, occurred in 42% of patients, with Grade or infections in 38% and fatal infections in 4% [see Adverse Reactions (6.1)]. The most common serious infection reported (>=10%) were pneumonia and sepsis. Two cases of progressive multifocal leukoencephalopathy (PML) occurred in patients receiving LYNOZYFIC.Monitor patients for signs and symptoms of infection and immunoglobulin levels prior to and during treatment with LYNOZYFIC and treat appropriately. Administer prophylactic antimicrobials, antibiotics, antifungals, antivirals, vaccines, and subcutaneous or intravenous immunoglobulin (IVIG) according to guidelines, including prophylaxis for PJP and herpesviruses [see Dosage and Administration (2.3)].Withhold LYNOZYFIC or consider permanent discontinuation of LYNOZYFIC based on severity of the infection [see Dosage and Administration (2.5)].. 5.5Neutropenia. LYNOZYFIC can cause neutropenia and febrile neutropenia. In patients who received LYNOZYFIC at the recommended dose in LINKER-MM1, decreased neutrophil count occurred in 62% of patients with Grade or decreased neutrophil count in 47%. Febrile neutropenia occurred in 8% of patients [see Adverse Reactions (6.1)].Monitor complete blood cell counts at baseline and periodically during treatment and provide supportive care per local guidelines. Monitor patients with neutropenia for signs of infection. Withhold LYNOZYFIC based on severity [see Dosage and Administration (2.5)].. 5.6Hepatotoxicity. LYNOZYFIC can cause hepatotoxicity. In LINKER-MM1, elevated ALT occurred in 46% of patients, with Grade or ALT elevation occurring in 6%; elevated AST occurred in 61% of patients, with Grade or AST elevation occurring in 10% of patients who received the recommended dose. Grade or total bilirubin elevations occurred in 1.7% of patients [see Adverse Reactions (6.1)]. Liver enzyme elevation can occur with or without concurrent CRS.Monitor liver enzymes and bilirubin at baseline and during treatment as clinically indicated. Withhold LYNOZYFIC or consider permanent discontinuation of LYNOZYFIC based on severity [see Dosage and Administration (2.5)]. 5.7Embryo-Fetal Toxicity. Based on its mechanism of action, LYNOZYFIC may cause fetal harm when administered to pregnant woman. Advise pregnant women of the potential risk to the fetus. Advise females of reproductive potential to use effective contraception during treatment with LYNOZYFIC and for months after the last dose [see Use in Specific Populations (8.1, 8.3)].