DOSAGE FORMS & STRENGTHS SECTION.

3 DOSAGE FORMS AND STRENGTHS ELREXFIO injection is clear to slightly opalescent, and colorless to pale brown liquid solution available as:o76 mg/1.9 mL (40 mg/mL) in single-dose vialo44 mg/1.1 mL (40 mg/mL) in single-dose vial. o76 mg/1.9 mL (40 mg/mL) in single-dose vial. o44 mg/1.1 mL (40 mg/mL) in single-dose vial. Injection:o76 mg/1.9 mL (40 mg/mL) in single-dose vial. (3)o44 mg/1.1 mL (40 mg/mL) in single-dose vial. (3). o76 mg/1.9 mL (40 mg/mL) in single-dose vial. (3). o44 mg/1.1 mL (40 mg/mL) in single-dose vial. (3).

DRUG INTERACTIONS SECTION.

7 DRUG INTERACTIONS For certain CYP substrates, minimal changes in the concentration may lead to serious adverse reactions. Monitor for toxicity or drug concentrations of such CYP substrates when co-administered with ELREXFIO.ELREXFIO causes release of cytokines [see Clinical Pharmacology (12.2)] that may suppress activity of cytochrome P450 (CYP) enzymes, resulting in increased exposure of CYP substrates. Increased exposure of CYP substrates is more likely to occur after the first dose of ELREXFIO Day and up to 14 days after the 32 mg dose on Day 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 ELREXFIO 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 ELREXFIO.Contraception Females Advise females of reproductive potential to use effective contraception during treatment and for months after the last dose of ELREXFIO.

GERIATRIC USE SECTION.

8.5 Geriatric Use Of the 183 patients with relapsed or refractory multiple myeloma treated with ELREXFIO in MagnetisMM-3 at the recommended dosage, 62% were 65 years of age or older, and 19% were 75 years of age or older. No overall differences in safety or effectiveness were observed in patients 65-74 years of age compared to younger patients. Clinical studies did not include sufficient numbers of patients 75 years of age or older to determine whether they respond differently from younger patients.

ADVERSE REACTIONS SECTION.

6 ADVERSE REACTIONS The following adverse reactions are discussed elsewhere in labeling:oCytokine Release Syndrome [see Warnings and Precautions (5.1)].oNeurologic Toxicity, Including ICANS [see Warnings and Precautions (5.2)].oInfections [see Warnings and Precautions (5.4)].oNeutropenia [see Warnings and Precautions (5.5)].oHepatotoxicity [see Warnings and Precautions (5.6)].. oCytokine Release Syndrome [see Warnings and Precautions (5.1)].. oNeurologic Toxicity, Including ICANS [see Warnings and Precautions (5.2)].. oInfections [see Warnings and Precautions (5.4)].. oNeutropenia [see Warnings and Precautions (5.5)].. oHepatotoxicity [see Warnings and Precautions (5.6)].. Most common adverse reactions (incidence >=20%) are CRS, fatigue, injection site reaction, diarrhea, upper respiratory tract infection, musculoskeletal pain, pneumonia, decreased appetite, rash, cough, nausea, and pyrexia.The most common Grade to laboratory abnormalities (>=30%) are decreased lymphocytes, decreased neutrophils, decreased hemoglobin, decreased white blood cells, and decreased platelets. (6.1) To report SUSPECTED ADVERSE REACTIONS, contact Pfizer Inc. at 1-800-438-1985 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/Refractory Multiple MyelomaMagnetisMM-3The safety of ELREXFIO was evaluated in MagnetisMM-3 [see Clinical Studies (14)]. The safety population described (n 183) includes patients who received the recommended dosage regimen of 12 mg subcutaneously on Day 1, 32 mg on Day 4, and 76 mg once weekly starting on Day 8. Among patients who received ELREXFIO, 42% were exposed for months or longer and 9% were exposed for one year or longer.The median age of patients who received ELREXFIO was 68 years (range: 36 to 88 years); 48% were female; 61% were White, 10% were Hispanic/Latino, 9% were Asian, and 6% were Black or African American.Serious adverse reactions occurred in 68% of patients who received ELREXFIO at the recommended dosing schedule. Serious adverse reactions in >2% of patients included pneumonia (25%), sepsis (13%), CRS (13%), upper respiratory tract infection (4.4%), acute kidney injury (3.8%), urinary tract infection (3.3%), COVID-19 (3.3%), encephalopathy (3.3%), pyrexia (2.2%), and febrile neutropenia (2.2%). Fatal adverse reactions occurred in 10% of patients including pneumonia (3.3%), sepsis (2.7%), acute respiratory distress syndrome (0.5%), cardio-respiratory arrest (0.5%), cardiogenic shock (0.5%), cardiopulmonary failure (0.5%), COVID-19 (0.5%), failure to thrive (0.5%), and pulmonary embolism (0.5%).Permanent discontinuations of ELREXFIO due to an adverse reaction occurred in 17% of patients. Adverse reactions which resulted in permanent discontinuation of ELREXFIO in >2% of patients included septic shock (2.2%).Dosage interruptions of ELREXFIO due to an adverse reaction occurred in 73% of patients. Adverse reactions which resulted in dose interruptions of ELREXFIO in >5% of patients included neutropenia, pneumonia, COVID-19, upper respiratory tract infection, thrombocytopenia, and anemia.The most common adverse reactions (>=20%) were CRS, fatigue, injection site reaction, diarrhea, upper respiratory tract infection, musculoskeletal pain, pneumonia, decreased appetite, rash, cough, nausea, and pyrexia. The most common Grade to laboratory abnormalities (>=30%) were decreased lymphocytes, decreased neutrophils, decreased hemoglobin, decreased white blood cells, and decreased platelets.Table summarizes adverse reactions in MagnetisMM-3.Table 8. Adverse Reactions (>=10%) in Patients with Relapsed or Refractory Multiple Myeloma Who Received ELREXFIO in MagnetisMM-3Adverse reactions were graded based on CTCAE Version 5.0, with the exception of CRS, which was graded based on the ASTCT 2019 criteria.System Organ ClassPreferred TermELREXFION 183All Grades(%)Grade or 4(%)Immune system disordersCytokine release syndrome580.5Only grade adverse reactions occurred. HypogammaglobulinemiaIncludes other related terms. 132.2 General disorders and site administration conditionsFatigue 436 Injection site reaction 370Pyrexia212.7 Edema 181.1 Gastrointestinal disordersDiarrhea361.1 Nausea210Constipation140Vomiting140InfectionsUpper respiratory tract infection 364.9PneumoniaPneumonia includes COVID-19 pneumonia, lower respiratory tract infection, lower respiratory tract infection viral, pneumocystis jirovecii pneumonia, pneumonia, pneumonia adenoviral, pneumonia bacterial, pneumonia cytomegaloviral, pneumonia fungal, pneumonia influenzal, pneumonia pseudomonal, pneumonia viral. 3219SepsisSepsis includes bacteremia, device related bacteremia, device related sepsis, escherichia bacteremia, escherichia sepsis, klebsiella sepsis, pseudomonal sepsis, sepsis, septic shock, staphylococcal bacteremia, staphylococcal sepsis, streptococcal sepsis, urosepsis. 1511Urinary tract infection 124.4 Musculoskeletal and connective tissue disordersMusculoskeletal pain 342.7 Metabolism and nutrition disordersDecreased appetite261.1 Skin and Subcutaneous Tissue disordersRashRash incudes erythema, palmar-plantar erythrodysesthesia syndrome, rash, rash erythematous, rash macular, rash maculo-papular, rash pustular, symmetrical drug-related intertriginous and flexural exanthema. 260Dry skin140Skin exfoliation 100Respiratory, thoracic and mediastinal disordersCough 240Dyspnea 153.3 Nervous system disordersHeadache180EncephalopathyEncephalopathy includes agitation, altered state of consciousness, cognitive disorder, confusional state, delirium, depressed level of consciousness, disorientation, hallucination, lethargy, memory impairment, metabolic encephalopathy, somnolence, toxic encephalopathy. 142.2Sensory neuropathySensory neuropathy includes burning sensation, dysesthesia, hypoesthesia, neuropathy peripheral, paresthesia, parosmia, peripheral sensorimotor neuropathy, peripheral sensory neuropathy, polyneuropathy, sensory loss. 130.5 Motor dysfunctionMotor dysfunction includes ataxia, balance disorder, gait disturbance, motor dysfunction, muscle contracture, muscle spasms, muscular weakness, peripheral motor neuropathy, peroneal nerve palsy, tremor. 141.1 Cardiac disordersCardiac arrhythmia 161.6Vascular disordersHemorrhage 131.6Psychiatric disordersInsomnia 130Injury, poisoning and procedural complicationsFall100.5 Clinically relevant adverse reactions in <10% of patients who received ELREXFIO included ICANS, febrile neutropenia, Guillain-Barre syndrome, abdominal pain, acute kidney injury, COVID-19, cardiac failure, congestion, thrombosis, cytomegalovirus infection, and progressive multifocal leukoencephalopathy. Table summarizes laboratory abnormalities in MagnetisMM-3.Table 9. Select Laboratory Abnormalities (>=30%) That Worsened from Baseline in Patients with Relapsed or Refractory Multiple Myeloma Who Received ELREXFIO in MagnetisMM-3Laboratory tests were graded according to NCI-CTCAE Version 5.0. Laboratory AbnormalityELREXFIOThe denominator used to calculate the rate varied from 181 to 183 based on the number of patients with baseline value and at least one post-treatment value.All Grades (%)Grade or (%)HematologyLymphocyte count decreased9184White blood cell decreased6940Hemoglobin decreased6843Neutrophil count decreased6251Platelet count decreased6132ChemistryAlbumin decreased556AST increase406Creatinine increased383.3Potassium decreased368ALT increase363.8Alkaline phosphatase increased341.1Creatinine clearance decreased3210.

BOXED WARNING SECTION.

WARNING: CYTOKINE RELEASE SYNDROME and NEUROLOGIC TOXICITY including IMMUNE EFFECTOR CELL-ASSOCIATED NEUROTOXICITY SYNDROME oCytokine Release Syndrome (CRS), including life-threatening or fatal reactions, can occur in patients receiving ELREXFIO. Initiate treatment with ELREXFIO step-up dosing schedule to reduce the risk of CRS. Withhold ELREXFIO until CRS resolves or permanently discontinue based on severity [see Dosage and Administration (2.2, 2.5), Warnings and Precautions (5.1)].oNeurologic toxicity, including Immune Effector Cell-Associated Neurotoxicity Syndrome (ICANS), and serious and life-threatening reactions, can occur in patients receiving ELREXFIO. Monitor patients for signs and symptoms of neurologic toxicity, including ICANS, during treatment. Withhold ELREXFIO until the neurologic toxicity resolves or permanently discontinue based on severity [see Dosage and Administration (2.5), Warnings and Precautions (5.2)].oBecause of the risk of CRS and neurologic toxicity, including ICANS, ELREXFIO is available only through restricted program under Risk Evaluation and Mitigation Strategy (REMS) called ELREXFIO REMS [see Warnings and Precautions (5.3)].. oCytokine Release Syndrome (CRS), including life-threatening or fatal reactions, can occur in patients receiving ELREXFIO. Initiate treatment with ELREXFIO step-up dosing schedule to reduce the risk of CRS. Withhold ELREXFIO until CRS resolves or permanently discontinue based on severity [see Dosage and Administration (2.2, 2.5), Warnings and Precautions (5.1)].. oNeurologic toxicity, including Immune Effector Cell-Associated Neurotoxicity Syndrome (ICANS), and serious and life-threatening reactions, can occur in patients receiving ELREXFIO. Monitor patients for signs and symptoms of neurologic toxicity, including ICANS, during treatment. Withhold ELREXFIO until the neurologic toxicity resolves or permanently discontinue based on severity [see Dosage and Administration (2.5), Warnings and Precautions (5.2)].. oBecause of the risk of CRS and neurologic toxicity, including ICANS, ELREXFIO is available only through restricted program under Risk Evaluation and Mitigation Strategy (REMS) called ELREXFIO REMS [see Warnings and Precautions (5.3)].. WARNING: CYTOKINE RELEASE SYNDROME and NEUROLOGIC TOXICITY including IMMUNE EFFECTOR CELL-ASSOCIATED NEUROTOXICITY SYNDROME See full prescribing information for complete boxed warning.oCytokine Release Syndrome (CRS), including life-threatening or fatal reactions, can occur in patients receiving ELREXFIO. Initiate treatment with ELREXFIO step-up dosing schedule to reduce risk of CRS. Withhold ELREXFIO until CRS resolves or permanently discontinue based on severity. (2.2, 2.5, 5.1)oNeurologic toxicity, including Immune Effector Cell-Associated Neurotoxicity Syndrome (ICANS), and serious and life-threatening reactions, can occur in patients receiving ELREXFIO. Monitor patients for signs and symptoms of neurologic toxicity, including ICANS, during treatment. Withhold ELREXFIO until the neurologic toxicity resolves or permanently discontinue based on severity. (2.5, 5.2)oELREXFIO is available only through restricted program called the ELREXFIO Risk Evaluation and Mitigation Strategy (REMS). (5.3). oCytokine Release Syndrome (CRS), including life-threatening or fatal reactions, can occur in patients receiving ELREXFIO. Initiate treatment with ELREXFIO step-up dosing schedule to reduce risk of CRS. Withhold ELREXFIO until CRS resolves or permanently discontinue based on severity. (2.2, 2.5, 5.1). oNeurologic toxicity, including Immune Effector Cell-Associated Neurotoxicity Syndrome (ICANS), and serious and life-threatening reactions, can occur in patients receiving ELREXFIO. Monitor patients for signs and symptoms of neurologic toxicity, including ICANS, during treatment. Withhold ELREXFIO until the neurologic toxicity resolves or permanently discontinue based on severity. (2.5, 5.2). oELREXFIO is available only through restricted program called the ELREXFIO Risk Evaluation and Mitigation Strategy (REMS). (5.3).

CARCINOGENESIS & MUTAGENESIS & IMPAIRMENT OF FERTILITY SECTION.

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

CLINICAL PHARMACOLOGY SECTION.

12 CLINICAL PHARMACOLOGY 12.1 Mechanism of Action Elranatamab-bcmm is bispecific B-cell maturation antigen (BCMA)-directed T-cell engaging antibody that binds BCMA on plasma cells, plasmablasts, and multiple myeloma cells and CD3 on T-cells leading to cytolysis of the BCMA-expressing cells. Elranatamab-bcmm activated T-cells, caused proinflammatory cytokine release, and resulted in multiple myeloma cell lysis.. 12.2 Pharmacodynamics Cytokine ConcentrationsTransient elevation of circulating cytokines IL-2, IL-6, IL-8, IL-10, TNF-, and IFN- was observed at dosage levels of 30 ug/kg (0.03 times the approved recommended dosage) and above. After administration of the approved recommended dosage of ELREXFIO, the highest elevation of cytokines was generally observed within 72 hours after first elranatamab-bcmm dose at 12 mg on Day 1, and generally returned to baseline prior to the administration of the first full dose 76 mg on Day 8.. 12.3 Pharmacokinetics Pharmacokinetic parameters are presented as geometric mean (coefficient of variation [CV]%) and are based upon subcutaneously administered unless otherwise specified.Elranatamab-bcmm exhibits dose proportional pharmacokinetics over dose range from to 76 mg (0.079 to times the approved recommended dosage). Elranatamab-bcmm maximum concentration [33.0 mcg/mL (46%)] is achieved at the end of weekly dosing regimen (i.e., at week 24 of 76 mg weekly dosing). Pharmacokinetic exposures are summarized for the recommended dosage of ELREXFIO in Table 10.Table 10. Pharmacokinetic Parameters of Elranatamab-bcmm in Subjects with Relapsed or Refractory Multiple MyelomaTimepointParametersCavg (mcg/mL)Cmax (mcg/mL)Ctrough (mcg/mL)First full 76 mg dose3.1 (94%)3.8 (94%)3.3 (102%)End of weekly dose (week 24)In patients who have achieved response. 32.0 (46%)33.0 (46%)30.5 (48%)Steady state (biweekly dosing) Steady state exposure of elranatamab biweekly dose is approximated at week 48. 17.7 (53%)19.5 (51%)15.1 (60%)Steady state (every weeks dosing) Steady state exposure of elranatamab once every weeks dose is approximated at week 72. 8.8 (58%)11.5 (54%)5.9 (78%)Absorption The mean bioavailability of elranatamab-bcmm was 56.2% when administered subcutaneously. The median (min, max) Tmax after elranatamab SC administration was (3 to 7) days.DistributionThe steady state volume of distribution of elranatamab-bcmm was 7.76 (33%).EliminationThe half-life of elranatamab-bcmm is 22 (64%) days at the 76 mg dosage, with clearance of 0.324 L/day (100%) following 24 weeks dosing. MetabolismElranatamab-bcmm is expected to be metabolized into small peptides by catabolic pathways.Specific PopulationsNo clinically significant differences in the pharmacokinetics of elranatamab-bcmm were observed based on age (36 to 89 years), sex, race (White, Asian, or Black), body weight (37 to 160 kg), mild or moderate renal impairment (estimated glomerular filtration rate [eGFR] by Modification of Diet in Renal Disease [MDRD] method: 30 to 89 mL/min), or mild hepatic impairment (total bilirubin to <=1.5 ULN or any AST greater than ULN).The effects of severe renal impairment (eGFR 15 to 29 mL/min), end-stage renal disease (eGFR <15 mL/min), or moderate to severe hepatic impairment (total bilirubin >1.5 times ULN and any AST) on the PK of elranatamab-bcmm are unknown. 12.6 Immunogenicity 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 studies described below with the incidence of anti-drug antibodies in other studies, including those of elranatamab-bcmm or of other elranatamab products.In the MagnetisMM-3 study, of the 168 participant who received recommended step-up and full dosage of ELREXFIO for up to 36 months and are evaluable for presence of ADA against elranatamab-bcmm, 9.5% (16/168) of patients tested positive for anti-elranatamab-bcmm-antibodies. Among the 16 patients who tested positive for ADAs, 56% (9/16) tested positive for neutralizing antibodies against elranatamab-bcmm. The effect of these antibodies on the pharmacokinetics, pharmacodynamics, safety, and/or effectiveness of ELREXFIO products is unknown.

CLINICAL STUDIES SECTION.

14 CLINICAL STUDIES 14.1 Relapsed or Refractory Multiple Myeloma The efficacy of ELREXFIO monotherapy was evaluated in patients with relapsed or refractory multiple myeloma in an open-label, single arm, multi-center study (MagnetisMM-3, NCT04649359). The study included patients who were refractory to at least one proteasome inhibitor (PI), one immunomodulatory agent (IMiD), and one anti-CD38 monoclonal antibody. MagnetisMM-3 included 123 patients naive to prior BCMA-directed therapy (pivotal Cohort A) and 64 patients with prior BCMA-directed antibody drug conjugate (ADC) or chimeric antigen receptor (CAR) T-cell therapy (supportive Cohort B). Patients had measurable disease by International Myeloma Working Group (IMWG) criteria at enrollment. The study included patients with an Eastern Cooperative Oncology Group (ECOG) score of <=2, adequate baseline bone marrow (absolute neutrophil count >=1.0 109/L, platelet count >=25 109/L, hemoglobin level >=8 g/dL), renal (CrCL >= 30 mL/min), and hepatic (AST and ALT <=2.5 ULN, total bilirubin <=2 ULN) function, and left-ventricular ejection fraction >=40%. Patients with stem cell transplant within 12 weeks prior to enrollment and active infections were excluded from the study. Eligible patients received subcutaneous administration of ELREXFIO at step-up doses of 12 mg on Day and 32 mg on Day of treatment, followed by the first treatment dose of ELREXFIO (76 mg) on Day of treatment. Thereafter, patients received 76 mg once weekly. After 24 weeks, in patients who achieved an IMWG response category of partial response or better with responses persisting for at least months, the dose interval was changed from every week to every weeks.The 123 patients enrolled in pivotal Cohort had received median of prior lines of therapy (range: to 22). Ninety-seven patients who were not exposed to prior BCMA-directed therapy and received at least four prior lines of therapy comprised the efficacy population. Among the 97 patients in the efficacy population, the median age was 69 (range: 46 to 89) years with 18.6% of patients >=75 years of age. Forty percent were female; 59.8% were White, 13.4% were Asian, 7.2% were Hispanic/Latino, 5.2% were Black or African American. Disease stage (R-ISS) at study entry was 20.6% in Stage I, 53.6% in Stage II, and 17.5% in Stage III. The median time since initial diagnosis of multiple myeloma to enrollment was 79.6 (range: 16 to 228) months. 96.9% were triple-class refractory, and 94.8% were refractory to their last line of therapy. 69.1% received prior autologous stem cell transplantation, and 7.2% received prior allogenic stem cell transplantation. High-risk cytogenetics [t(4;14), t(14;16), or del(17p)] were present in 22.7% of patients. 34.0% of patients had extramedullary disease at baseline by BICR.Efficacy was based on response rate and duration of response (DOR), as assessed by BICR based on IMWG criteria. Efficacy results from BCMA-directed therapy naive patients are shown in Table 11. The median (range) time to first response (TTR) was 1.22 (0.9 to 6.5) months. With median follow-up of 11.1 months (95% CI: 10.6, 12.0) among responders, the DOR rate at months was 90.4% (95% CI: 78.4%, 95.9%) and at months was 82.3% (95% CI: 67.1%, 90.9%).Table 11. Efficacy Results from BCMA-directed Therapy Naive PatientsAbbreviations: CI Confidence interval; NR Not reached; NE Not estimable.N 97Objective Response Rate (ORR: sCR+CR+VGPR+PR), (%) (95% CI)56 (57.7%)(47.3, 67.7) Complete response (CR) or betterComplete response or better Stringent complete response (sCR) complete response (CR). 25 (25.8%) Very good partial response (VGPR)25 (25.8%) Partial response (PR)6 (6.2%)Duration of Response (DOR) (months) Median (95% CI)NR (12.0, NE)Among the 64 patients enrolled in Cohort who previously received PI, an IMiD, an anti-CD38 monoclonal antibody, and BCMA-directed therapy, 63 patients received at least four prior lines of therapy. Patients had received median of prior lines of therapy (range: to 19); 73% and 32% received prior BCMA-directed ADC and CAR T-cell therapy, respectively.Confirmed ORR by BICR was 33.3% (95% CI: 22.0, 46.3). After median (95% CI) follow-up of 10.2 (9.9, 11) months among responders, median DOR was not reached (95% CI: NE, NE) and the DOR rate at months was 84.3% (95% CI: 58.7, 94.7).

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/Refractory Multiple MyelomaMagnetisMM-3The safety of ELREXFIO was evaluated in MagnetisMM-3 [see Clinical Studies (14)]. The safety population described (n 183) includes patients who received the recommended dosage regimen of 12 mg subcutaneously on Day 1, 32 mg on Day 4, and 76 mg once weekly starting on Day 8. Among patients who received ELREXFIO, 42% were exposed for months or longer and 9% were exposed for one year or longer.The median age of patients who received ELREXFIO was 68 years (range: 36 to 88 years); 48% were female; 61% were White, 10% were Hispanic/Latino, 9% were Asian, and 6% were Black or African American.Serious adverse reactions occurred in 68% of patients who received ELREXFIO at the recommended dosing schedule. Serious adverse reactions in >2% of patients included pneumonia (25%), sepsis (13%), CRS (13%), upper respiratory tract infection (4.4%), acute kidney injury (3.8%), urinary tract infection (3.3%), COVID-19 (3.3%), encephalopathy (3.3%), pyrexia (2.2%), and febrile neutropenia (2.2%). Fatal adverse reactions occurred in 10% of patients including pneumonia (3.3%), sepsis (2.7%), acute respiratory distress syndrome (0.5%), cardio-respiratory arrest (0.5%), cardiogenic shock (0.5%), cardiopulmonary failure (0.5%), COVID-19 (0.5%), failure to thrive (0.5%), and pulmonary embolism (0.5%).Permanent discontinuations of ELREXFIO due to an adverse reaction occurred in 17% of patients. Adverse reactions which resulted in permanent discontinuation of ELREXFIO in >2% of patients included septic shock (2.2%).Dosage interruptions of ELREXFIO due to an adverse reaction occurred in 73% of patients. Adverse reactions which resulted in dose interruptions of ELREXFIO in >5% of patients included neutropenia, pneumonia, COVID-19, upper respiratory tract infection, thrombocytopenia, and anemia.The most common adverse reactions (>=20%) were CRS, fatigue, injection site reaction, diarrhea, upper respiratory tract infection, musculoskeletal pain, pneumonia, decreased appetite, rash, cough, nausea, and pyrexia. The most common Grade to laboratory abnormalities (>=30%) were decreased lymphocytes, decreased neutrophils, decreased hemoglobin, decreased white blood cells, and decreased platelets.Table summarizes adverse reactions in MagnetisMM-3.Table 8. Adverse Reactions (>=10%) in Patients with Relapsed or Refractory Multiple Myeloma Who Received ELREXFIO in MagnetisMM-3Adverse reactions were graded based on CTCAE Version 5.0, with the exception of CRS, which was graded based on the ASTCT 2019 criteria.System Organ ClassPreferred TermELREXFION 183All Grades(%)Grade or 4(%)Immune system disordersCytokine release syndrome580.5Only grade adverse reactions occurred. HypogammaglobulinemiaIncludes other related terms. 132.2 General disorders and site administration conditionsFatigue 436 Injection site reaction 370Pyrexia212.7 Edema 181.1 Gastrointestinal disordersDiarrhea361.1 Nausea210Constipation140Vomiting140InfectionsUpper respiratory tract infection 364.9PneumoniaPneumonia includes COVID-19 pneumonia, lower respiratory tract infection, lower respiratory tract infection viral, pneumocystis jirovecii pneumonia, pneumonia, pneumonia adenoviral, pneumonia bacterial, pneumonia cytomegaloviral, pneumonia fungal, pneumonia influenzal, pneumonia pseudomonal, pneumonia viral. 3219SepsisSepsis includes bacteremia, device related bacteremia, device related sepsis, escherichia bacteremia, escherichia sepsis, klebsiella sepsis, pseudomonal sepsis, sepsis, septic shock, staphylococcal bacteremia, staphylococcal sepsis, streptococcal sepsis, urosepsis. 1511Urinary tract infection 124.4 Musculoskeletal and connective tissue disordersMusculoskeletal pain 342.7 Metabolism and nutrition disordersDecreased appetite261.1 Skin and Subcutaneous Tissue disordersRashRash incudes erythema, palmar-plantar erythrodysesthesia syndrome, rash, rash erythematous, rash macular, rash maculo-papular, rash pustular, symmetrical drug-related intertriginous and flexural exanthema. 260Dry skin140Skin exfoliation 100Respiratory, thoracic and mediastinal disordersCough 240Dyspnea 153.3 Nervous system disordersHeadache180EncephalopathyEncephalopathy includes agitation, altered state of consciousness, cognitive disorder, confusional state, delirium, depressed level of consciousness, disorientation, hallucination, lethargy, memory impairment, metabolic encephalopathy, somnolence, toxic encephalopathy. 142.2Sensory neuropathySensory neuropathy includes burning sensation, dysesthesia, hypoesthesia, neuropathy peripheral, paresthesia, parosmia, peripheral sensorimotor neuropathy, peripheral sensory neuropathy, polyneuropathy, sensory loss. 130.5 Motor dysfunctionMotor dysfunction includes ataxia, balance disorder, gait disturbance, motor dysfunction, muscle contracture, muscle spasms, muscular weakness, peripheral motor neuropathy, peroneal nerve palsy, tremor. 141.1 Cardiac disordersCardiac arrhythmia 161.6Vascular disordersHemorrhage 131.6Psychiatric disordersInsomnia 130Injury, poisoning and procedural complicationsFall100.5 Clinically relevant adverse reactions in <10% of patients who received ELREXFIO included ICANS, febrile neutropenia, Guillain-Barre syndrome, abdominal pain, acute kidney injury, COVID-19, cardiac failure, congestion, thrombosis, cytomegalovirus infection, and progressive multifocal leukoencephalopathy. Table summarizes laboratory abnormalities in MagnetisMM-3.Table 9. Select Laboratory Abnormalities (>=30%) That Worsened from Baseline in Patients with Relapsed or Refractory Multiple Myeloma Who Received ELREXFIO in MagnetisMM-3Laboratory tests were graded according to NCI-CTCAE Version 5.0. Laboratory AbnormalityELREXFIOThe denominator used to calculate the rate varied from 181 to 183 based on the number of patients with baseline value and at least one post-treatment value.All Grades (%)Grade or (%)HematologyLymphocyte count decreased9184White blood cell decreased6940Hemoglobin decreased6843Neutrophil count decreased6251Platelet count decreased6132ChemistryAlbumin decreased556AST increase406Creatinine increased383.3Potassium decreased368ALT increase363.8Alkaline phosphatase increased341.1Creatinine clearance decreased3210.

CONTRAINDICATIONS SECTION.

4 CONTRAINDICATIONS None.. None. (4).

DESCRIPTION SECTION.

11 DESCRIPTION Elranatamab-bcmm is bispecific B-cell maturation antigen (BCMA)-directed CD3 T-cell engager. It is bispecific, humanized immunoglobulin 2-alanine (IgG2a) kappa antibody derived from two monoclonal antibodies (mAbs), an anti-BCMA mAb and an anti-CD3 mAb. Each of these mAbs contributes one distinct heavy (H) chain and one distinct light (L) chain to the bispecific elranatamab-bcmm. The resulting 4-chain bispecific antibody is covalently linked via five inter-chain disulfide bonds. Elranatamab-bcmm is produced using two recombinant Chinese hamster ovary (CHO) cell lines, one that contains the DNA encoding the sequence for anti-BCMA monoclonal antibody (mAb) and one that contains the sequence for anti-CD3 mAb, which are grown separately in suspension culture using chemically-defined (CD), animal-derived component-free (ACF) media. The molecular weight of elranatamab-bcmm is approximately 148.5 kDa.ELREXFIO(R) (elranatamab-bcmm) injection is sterile, preservative-free, clear to slightly opalescent, and colorless to pale brown liquid solution for subcutaneous administration. ELREXFIO (elranatamab-bcmm) is supplied at concentration of 40 mg/mL in either 76 mg/1.9 mL or 44 mg/1.1 mL single-dose vials. Each mL of solution contains 40 mg elranatamab-bcmm, edetate disodium (0.045 mg), histidine (1.12 mg), L-histidine hydrochloride monohydrate (2.67 mg), polysorbate 80 (0.2 mg), sucrose (85 mg) and Water for Injection. The pH is 5.8.

DOSAGE & ADMINISTRATION SECTION.

2 DOSAGE AND ADMINISTRATION ELREXFIO Dosing Schedule (2.2)Dosing ScheduleDayELREXFIO DoseStep-up Dosing ScheduleDay 1Step-up dose 112 mgDay 4Step-up dose 232 mgDay 8First treatment dose76 mgWeekly Dosing ScheduleOne week after first treatment dose and weekly thereafter through week 24Subsequent treatment doses76 mgBiweekly (Every Week) Dosing ScheduleResponders only week 25 onward. Week 25 and every weeks thereafter through week 48Subsequent treatment doses76 mgEvery Week Dosing ScheduleIn patients who have maintained the response following 24 weeks of treatment at the biweekly dosing schedule. Week 49 and every weeks thereafterSubsequent treatment doses76 mgoPatients should be hospitalized for 48 hours after administration of the first step-up dose, and for 24 hours after administration of the second step-up dose. (2.1)oFor subcutaneous injection only. (2.2)oAdminister pre-treatment medications as recommended. (2.3)oSee Full Prescribing Information for instructions on preparation and administration. (2.6). oPatients should be hospitalized for 48 hours after administration of the first step-up dose, and for 24 hours after administration of the second step-up dose. (2.1). oFor subcutaneous injection only. (2.2). oAdminister pre-treatment medications as recommended. (2.3). oSee Full Prescribing Information for instructions on preparation and administration. (2.6). 2.1 Important Dosing Information Administer ELREXFIO subcutaneously according to the step-up dosing schedule to reduce the incidence and severity of cytokine release syndrome (CRS).Administer pre-treatment medications prior to each dose in the ELREXFIO step-up dosing schedule, which includes step-up dose 1, step-up dose 2, and the first treatment dose as recommended [see Dosage and Administration (2.2, 2.3)].ELREXFIO should only be administered by qualified healthcare professional with appropriate medical support to manage severe reactions such as CRS and neurologic toxicity, including ICANS [see Warnings and Precautions (5.1, 5.2)].Due to the risk of CRS, patients should be hospitalized for 48 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 For subcutaneous injection only.The recommended dosing schedule for ELREXFIO is provided in Table 1. The recommended dosages of ELREXFIO subcutaneous injection are: step-up dose of 12 mg on Day 1, step-up dose of 32 mg on Day 4, followed by the first treatment dose of 76 mg on Day 8, and then 76 mg weekly thereafter through week 24.For patients who have received at least 24 weeks of treatment with ELREXFIO and have achieved response [partial response (PR) or better] and maintained this response for at least months, the dose interval should transition to an every two-week schedule. For patients who have received at least 24 weeks of treatment with ELREXFIO at the every two-week dosing schedule and have maintained the response, the dose interval should transition to an every four-week schedule. Continue treatment with ELREXFIO until disease progression or unacceptable toxicity.Administer pre-treatment medications prior to each dose in the ELREXFIO step-up dosing schedule, which includes step-up dose 1, step-up dose 2, and the first treatment dose as recommended [see Dosage and Administration (2.3)].Table 1. ELREXFIO Dosing ScheduleNote: See Table for recommendations on restarting ELREXFIO after dose delays.Dosing ScheduleDayELREXFIO DoseStep-up Dosing ScheduleDay 1Administer pre-treatment medications prior to each dose in the ELREXFIO step-up dosing schedule, which includes step-up dose 1, step-up dose 2, and the first treatment dose [see Dosage and Administration (2.3)]. Step-up dose 112 mgDay A minimum of days should be maintained between step-up dose (12 mg) and step-up dose (32 mg). Step-up dose 232 mgDay A minimum of days should be maintained between step-up dose (32 mg) and the first treatment (76 mg) dose. First treatment dose76 mgWeekly Dosing ScheduleOne week after first treatment dose and weekly thereafterA minimum of days should be maintained between treatment doses. through week 24Subsequent treatment doses76 mgBiweekly (Every Week) Dosing ScheduleResponders only week 25 onwardWeek 25 and every weeks thereafter through week 48Subsequent treatment doses76 mgEvery Week Dosing ScheduleIn patients who have maintained the response following 24 weeks of treatment at the biweekly dosing scheduleWeek 49 and every weeks thereafter Subsequent treatment doses76 mg. 2.3 Recommended Pre-treatment Medications Administer the following pre-treatment medications approximately hour before the first three doses of ELREXFIO in the step-up dosing schedule, which includes step-up dose 1, step-up dose 2, and the first treatment dose as described in Table to reduce the risk of CRS [see Warnings and Precautions (5.1)]:oacetaminophen (or equivalent) 650 mg orallyodexamethasone (or equivalent) 20 mg orally or intravenously odiphenhydramine (or equivalent) 25 mg orally. oacetaminophen (or equivalent) 650 mg orally. odexamethasone (or equivalent) 20 mg orally or intravenously odiphenhydramine (or equivalent) 25 mg orally. 2.4 Restarting ELREXFIO After Dosage Delay If dose of ELREXFIO is delayed, restart therapy based on the recommendations listed in Table and resume the dosing schedule accordingly [see Dosage and Administration (2.2) ]. Administer pre-treatment medications as indicated in Table 2.Table 2. Recommendation for Restarting Therapy with ELREXFIO After Dosage DelayLast Dose AdministeredTime Since the Last Dose AdministeredAction for Next DoseStep-up dose (12 mg)2 weeks or less (<=14 days)Restart ELREXFIO at step-up dose (32 mg).Administer pre-treatment medications prior to the ELREXFIO dose [see Dosage and Administration (2.3) ]. If tolerated, increase to 76 mg days later.Greater than weeks (>14 days)Restart ELREXFIO step-up dosing schedule at step-up dose (12 mg). Step-up dose (32 mg)2 weeks or less (<=14 days)Restart ELREXFIO at 76 mg. Greater than weeks to less than or equal to weeks (15 days to <=28 days)Restart ELREXFIO at step-up dose (32 mg). If tolerated, increase to 76 mg week later. Greater than weeks (>28 days)Restart ELREXFIO step-up dosing schedule at step-up dose (12 mg). Any weekly treatment dose (76 mg)8 weeks or less (<=56 days)Restart ELREXFIO at 76 mg.Greater than weeks to less or equal to 12 weeks (57 days to <=84 days)Consider benefit-risk of restarting ELREXFIO in patients who require dose delay of more than 56 days due to an adverse reaction.Restart ELREXFIO at step-up dose (32 mg).If tolerated, increase to 76 mg week later.Greater than 12 weeks (>84 days)Restart ELREXFIO step-up dosing schedule at step-up dose (12 mg).Any biweekly or every-4-week treatment dose (76 mg)12 weeks or less (<=84 days) Restart ELREXFIO at 76 mg.Greater than 12 weeks (>84 days) Restart ELREXFIO step-up dosing schedule at step-up dose (12 mg). 2.5 Dosage Modifications for Adverse Reactions Dosage reductions of ELREXFIO are not recommended. Dosage delays may be required to manage toxicities related to ELREXFIO [see Warnings and Precautions (5)]. Recommendations on restarting ELREXFIO after dose delay are provided in Table 2.See Table and Table for recommended actions for adverse reactions of CRS and ICANS, respectively. See Table for recommended actions for neurologic toxicity excluding ICANS and Table for recommended actions for other adverse reactions following administration of ELREXFIO. Consider further management per current practice guidelines.Management of CRS, Neurologic Toxicity Including ICANS Cytokine Release Syndrome (CRS) Management recommendations for CRS are summarized in Table 3. Identify 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 ELREXFIO until CRS resolves. Manage CRS according to the recommendations in Table and consider further management per current practice guidelines. Administer supportive therapy for CRS, which may include intensive care for severe or life-threatening CRS. Consider laboratory testing to monitor for disseminated intravascular coagulation (DIC), hematology parameters, as well as pulmonary, cardiac, renal, and hepatic function.Table 3. Recommendations for Management of CRSGradeBased on American Society for Transplantation and Cellular Therapy (ASTCT) 2019 grading criteria for CRS.Presenting SymptomsActionsGrade 1Temperature >=100.4 (38 C)Attributed to CRS. Fever may not always be present concurrently with hypotension or hypoxia as it may be masked by interventions such as antipyretics or anti-cytokine therapy. oWithhold ELREXFIO until CRS resolves.See Table for recommendations on restarting ELREXFIO after dose delays.oAdminister pretreatment medications prior to next dose of ELREXFIO.Grade 2Temperature >=100.4 (38 C) with either:oHypotension responsive to fluid and not requiring vasopressors, and/oroOxygen requirement of low-flow nasal cannulaLow-flow nasal cannula is <=6 L/min, and high-flow nasal cannula is >6 L/min. or blow-byoWithhold ELREXFIO until CRS resolves.oMonitor patients daily for 48 hours following the next dose of ELREXFIO. Instruct patients to remain within proximity of healthcare facility, and consider hospitalization.oAdminister pretreatment medications prior to next dose of ELREXFIO.Grade 3(First occurrence)Temperature >=100.4 (38 C) with either:oHypotension requiring one vasopressor with or without vasopressin, and/oroOxygen requirement of high-flow nasal cannula, facemask, non-rebreather mask, or Venturi maskoWithhold ELREXFIO until CRS resolves.oProvide supportive therapy, which may include intensive care.oPatients should be hospitalized for 48 hours following the next dose of ELREXFIO.oAdminister pretreatment medications prior to next dose of ELREXFIO.Grade (Recurrent)Temperature >=100.4 (38 C) with either:oHypotension requiring one vasopressor with or without vasopressin, and/oroOxygen requirement of high-flow nasal cannula, facemask, non-rebreather mask, or Venturi maskoPermanently discontinue therapy with ELREXFIO.oProvide supportive therapy, which may include intensive care.Grade 4Temperature >=100.4 (38 C) with either:oHypotension requiring multiple vasopressors (excluding vasopressin), and/oroOxygen requirement of positive pressure (e.g., continuous positive airway pressure [CPAP], bilevel positive airway pressure [BiPAP], intubation, and mechanical ventilation)oPermanently discontinue therapy with ELREXFIO.oProvide supportive therapy, which may include intensive care.Neurologic Toxicity Including ICANS Management recommendations for ICANS and neurologic toxicity are summarized in Table and Table 5.At the first sign of neurologic toxicity, including ICANS, withhold ELREXFIO and consider neurology evaluation. Rule out other causes of neurologic symptoms. Provide supportive therapy, which may include intensive care, for severe or life-threatening neurologic toxicities, including ICANS [see Warnings and Precautions (5.2)]. Manage ICANS according to the recommendations in Table and consider further management per current practice guidelines.Table 4. Recommendations for Management of ICANSGradeBased on American Society for Transplantation and Cellular Therapy (ASTCT) 2019 grading criteria for ICANS.Presenting SymptomsManagement is determined by the most severe event, not attributable to any other cause.ActionsGrade 1ICE score 7-9If 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. Or depressed level of consciousnessNot attributable to any other cause.: awakens spontaneously.oWithhold ELREXFIO until ICANS resolves.See Table for recommendations on restarting ELREXFIO after dose delays.oMonitor neurologic symptoms and consider consultation with neurologist and other specialists for further evaluation and management.oConsider non-sedating, anti-seizure medications (e.g., levetiracetam) for seizure prophylaxis.Grade 2ICE score 3-6 Or depressed level of consciousness: awakens to voice.oWithhold ELREXFIO until ICANS resolves.oAdminister dexamethasoneAll references to dexamethasone administration are dexamethasone or equivalent medications. 10 mg intravenously every hours. Continue dexamethasone use until resolution to Grade or less, then taper.oMonitor neurologic symptoms and consider consultation with neurologist and other specialists for further evaluation and management. oConsider non-sedating, anti-seizure medications (e.g., levetiracetam) for seizure prophylaxis. oMonitor patients daily for 48 hours following the next dose of ELREXFIO. Instruct patients to remain within proximity of healthcare facility, and consider hospitalization.Grade 3(First occurrence)ICE score 0-2 or depressed level of consciousness: awakens only to tactile stimulus, or seizures, either:oany clinical seizure, focal or generalized, that resolves rapidly, or onon-convulsive seizures on electroencephalogram (EEG) that resolve with intervention, or raised intracranial pressure: focal/local edema on neuroimaging oWithhold ELREXFIO until ICANS resolves.oAdminister dexamethasone 10 mg intravenously every hours. Continue dexamethasone use until resolution to Grade or less, then taper.oMonitor neurologic symptoms and consider consultation with neurologist and other specialists for further evaluation and management. oConsider non-sedating, anti-seizure medications (e.g., levetiracetam) for seizure prophylaxis. oProvide supportive therapy, which may include intensive care.oPatients should be hospitalized for 48 hours following the next dose of ELREXFIO.Grade (recurrent)ICE score 0-2 or depressed level of consciousness: awakens only to tactile stimulus, or seizures, either:oany clinical seizure, focal or generalized, that resolves rapidly, or onon-convulsive seizures on electroencephalogram (EEG) that resolve with intervention, or raised intracranial pressure: focal/local edema on neuroimaging oPermanently discontinue ELREXFIO.oAdminister dexamethasone 10 mg intravenously every hours. Continue dexamethasone use until resolution to Grade or less, then taper.oMonitor neurologic symptoms and consider consultation with neurologist and other specialists for further evaluation and management. oConsider non-sedating, anti-seizure medications (e.g., levetiracetam) for seizure prophylaxis. oProvide supportive therapy, which may include intensive care.Grade 4ICE score Or, depressed level of consciousness either:opatient is unarousable or requires vigorous or repetitive tactile stimuli to arouse, orostupor or coma, or seizures, either:olife-threatening prolonged seizure (>5 minutes), ororepetitive clinical or electrical seizures without return to baseline in between,or motor findings:odeep focal motor weakness such as hemiparesis or paraparesis, or raised intracranial pressure/cerebral edema, with signs/symptoms such as:odiffuse cerebral edema on neuroimaging, orodecerebrate or decorticate posturing, orocranial nerve VI palsy, oropapilledema, oroCushings triadoPermanently discontinue ELREXFIO.oAdminister dexamethasone 10 mg intravenously every hours. Continue dexamethasone use until resolution to Grade or less, then taper.oAlternatively, consider administration of methylprednisolone 1,000 mg per day intravenously for days.oMonitor neurologic symptoms and consider consultation with neurologist and other specialists for further evaluation and management. oConsider non-sedating, anti-seizure medications (e.g., levetiracetam) for seizure prophylaxis. oProvide supportive therapy, which may include intensive care.Table 5. Recommendations for Management of Neurologic Toxicity, Excluding ICANSAdverse ReactionSeverityActionsNeurologic Toxicity (excluding ICANS)Grade 1oWithhold ELREXFIO until neurologic toxicity symptoms resolve or stabilize.Grade 2Grade (First occurrence)oWithhold ELREXFIO until neurologic toxicity symptoms improve to Grade or less.oProvide supportive therapy.Grade (Recurrent)Grade 4oPermanently discontinue ELREXFIO.oProvide supportive therapy, which may include intensive care.Table 6. Recommended Dosage Modifications for Other Adverse ReactionsAdverse ReactionsSeverityActionsHematologic Adverse Reactions [see Warnings and Precautions (5.5)]Absolute neutrophil count less than 0.5 109/LoWithhold ELREXFIO until absolute neutrophil count is 0.5 109/L or higher.See Table for recommendations on restarting ELREXFIO after dose delays.Febrile neutropeniaoWithhold ELREXFIO until absolute neutrophil count is x 109/L or higher and fever resolves.Hemoglobin less than g/dLoWithhold ELREXFIO until hemoglobin is g/dL or higher.Platelet count less than 25,000/mcL Platelet count between 25,000/mcL and 50,000/mcL with bleedingoWithhold ELREXFIO until platelet count is 25,000/mcL or higher and no evidence of bleeding.Infections and Other Non-hematologic Adverse ReactionsBased on National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE), Version 5.0. [see Warnings and Precautions (5.4, 5.6) and Adverse Reactions (6.1)]Grade 3oWithhold ELREXFIO until adverse reaction improves to <=Grade or baseline. Grade 4oConsider permanent discontinuation of ELREXFIO.oIf ELREXFIO is not permanently discontinued, withhold subsequent treatment doses of ELREXFIO (e.g., doses administered after ELREXFIO step-up dosing schedule) until adverse reaction improves to Grade or less.. oWithhold ELREXFIO until CRS resolves.See Table for recommendations on restarting ELREXFIO after dose delays.. oAdminister pretreatment medications prior to next dose of ELREXFIO.. oHypotension responsive to fluid and not requiring vasopressors, and/or. oOxygen requirement of low-flow nasal cannulaLow-flow nasal cannula is <=6 L/min, and high-flow nasal cannula is >6 L/min. or blow-by. oWithhold ELREXFIO until CRS resolves.. oMonitor patients daily for 48 hours following the next dose of ELREXFIO. Instruct patients to remain within proximity of healthcare facility, and consider hospitalization.. oAdminister pretreatment medications prior to next dose of ELREXFIO.. oHypotension requiring one vasopressor with or without vasopressin, and/or. oOxygen requirement of high-flow nasal cannula, facemask, non-rebreather mask, or Venturi mask. oWithhold ELREXFIO until CRS resolves.. oProvide supportive therapy, which may include intensive care.. oPatients should be hospitalized for 48 hours following the next dose of ELREXFIO.. oAdminister pretreatment medications prior to next dose of ELREXFIO.. oHypotension requiring one vasopressor with or without vasopressin, and/or. oOxygen requirement of high-flow nasal cannula, facemask, non-rebreather mask, or Venturi mask. oPermanently discontinue therapy with ELREXFIO.. oProvide supportive therapy, which may include intensive care.. oHypotension requiring multiple vasopressors (excluding vasopressin), and/or. oOxygen requirement of positive pressure (e.g., continuous positive airway pressure [CPAP], bilevel positive airway pressure [BiPAP], intubation, and mechanical ventilation). oPermanently discontinue therapy with ELREXFIO.. oProvide supportive therapy, which may include intensive care.. oWithhold ELREXFIO until ICANS resolves.See Table for recommendations on restarting ELREXFIO after dose delays.. oMonitor neurologic symptoms and consider consultation with neurologist and other specialists for further evaluation and management.. oConsider non-sedating, anti-seizure medications (e.g., levetiracetam) for seizure prophylaxis.. oWithhold ELREXFIO until ICANS resolves.. oAdminister dexamethasoneAll references to dexamethasone administration are dexamethasone or equivalent medications. 10 mg intravenously every hours. Continue dexamethasone use until resolution to Grade or less, then taper.. oMonitor neurologic symptoms and consider consultation with neurologist and other specialists for further evaluation and management. oConsider non-sedating, anti-seizure medications (e.g., levetiracetam) for seizure prophylaxis. oMonitor patients daily for 48 hours following the next dose of ELREXFIO. Instruct patients to remain within proximity of healthcare facility, and consider hospitalization.. oany clinical seizure, focal or generalized, that resolves rapidly, or onon-convulsive seizures on electroencephalogram (EEG) that resolve with intervention, oWithhold ELREXFIO until ICANS resolves.. oAdminister dexamethasone 10 mg intravenously every hours. Continue dexamethasone use until resolution to Grade or less, then taper.. oMonitor neurologic symptoms and consider consultation with neurologist and other specialists for further evaluation and management. oConsider non-sedating, anti-seizure medications (e.g., levetiracetam) for seizure prophylaxis. oProvide supportive therapy, which may include intensive care.. oPatients should be hospitalized for 48 hours following the next dose of ELREXFIO.. oany clinical seizure, focal or generalized, that resolves rapidly, or onon-convulsive seizures on electroencephalogram (EEG) that resolve with intervention, oPermanently discontinue ELREXFIO.. oAdminister dexamethasone 10 mg intravenously every hours. Continue dexamethasone use until resolution to Grade or less, then taper.. oMonitor neurologic symptoms and consider consultation with neurologist and other specialists for further evaluation and management. oConsider non-sedating, anti-seizure medications (e.g., levetiracetam) for seizure prophylaxis. oProvide supportive therapy, which may include intensive care.. opatient is unarousable or requires vigorous or repetitive tactile stimuli to arouse, or. ostupor or coma, olife-threatening prolonged seizure (>5 minutes), or. orepetitive clinical or electrical seizures without return to baseline in between,. odeep focal motor weakness such as hemiparesis or paraparesis, odiffuse cerebral edema on neuroimaging, or. odecerebrate or decorticate posturing, or. ocranial nerve VI palsy, or. opapilledema, or. oCushings triad. oPermanently discontinue ELREXFIO.. oAdminister dexamethasone 10 mg intravenously every hours. Continue dexamethasone use until resolution to Grade or less, then taper.. oAlternatively, consider administration of methylprednisolone 1,000 mg per day intravenously for days.. oMonitor neurologic symptoms and consider consultation with neurologist and other specialists for further evaluation and management. oConsider non-sedating, anti-seizure medications (e.g., levetiracetam) for seizure prophylaxis. oProvide supportive therapy, which may include intensive care.. oWithhold ELREXFIO until neurologic toxicity symptoms resolve or stabilize.. oWithhold ELREXFIO until neurologic toxicity symptoms improve to Grade or less.. oProvide supportive therapy.. oPermanently discontinue ELREXFIO.. oProvide supportive therapy, which may include intensive care.. oWithhold ELREXFIO until absolute neutrophil count is 0.5 109/L or higher.See Table for recommendations on restarting ELREXFIO after dose delays.. oWithhold ELREXFIO until absolute neutrophil count is x 109/L or higher and fever resolves.. oWithhold ELREXFIO until hemoglobin is g/dL or higher.. oWithhold ELREXFIO until platelet count is 25,000/mcL or higher and no evidence of bleeding.. oWithhold ELREXFIO until adverse reaction improves to <=Grade or baseline. oConsider permanent discontinuation of ELREXFIO.. oIf ELREXFIO is not permanently discontinued, withhold subsequent treatment doses of ELREXFIO (e.g., doses administered after ELREXFIO step-up dosing schedule) until adverse reaction improves to Grade or less.. 2.6 Preparation and Administration Instructions ELREXFIO is intended for subcutaneous use by healthcare provider only. ELREXFIO should be administered by healthcare provider with adequate medical personnel and appropriate medical equipment to manage severe reactions, including CRS and neurologic toxicity, including ICANS [see Warnings and Precautions (5.1, 5.2)].ELREXFIO 76 mg/1.9 mL (40 mg/mL) vial and 44 mg/1.1 mL (40 mg/mL) vial are supplied as ready-to-use solution that do not need dilution prior to administration.ELREXFIO is clear to slightly opalescent, and colorless to pale brown liquid solution. Parenteral drug products should be inspected visually for particulate matter and discoloration prior to administration, whenever solution and container permit. Do not administer if solution is discolored or contains particulate matter.Use aseptic technique to prepare and administer ELREXFIO.PreparationELREXFIO vials are for one-time use in single patient and do not contain any preservatives. Prepare ELREXFIO following the instructions below (see Table 7) depending on the required dose.Table 7. Injection VolumesTotal Dose (mg)Volume of Injection12 mg0.3 mL32 mg0.8 mL76 mg1.9 mLRemove the appropriate strength ELREXFIO vial from refrigerated storage [2 to C (36 to 46 F)]. Once removed from refrigerated storage, equilibrate ELREXFIO to ambient temperature [15 to 30 (59 to 86 F)]. Do not warm ELREXFIO in any other way. Withdraw the required injection volume of ELREXFIO from the vial into an appropriately sized syringe with stainless steel injection needles (30G or wider) and polypropylene or polycarbonate syringe material. Discard unused portion.AdministrationInject the required volume of ELREXFIO into the subcutaneous tissue of the abdomen (preferred injection site). Alternatively, ELREXFIO may be injected into the subcutaneous tissue at other sites (e.g., thigh).Do not inject into tattoos or scars or areas where the skin is red, bruised, tender, hard or not intact.Storage of Prepared SyringeIf the prepared dosing syringe is not used immediately, the syringe may be stored refrigerated between C to C (36 to 46 F) for maximum of 72 hours or between C to 25 (46 to 77 F) for maximum of 24 hours. Once removed from refrigerated storage, the prepared syringe must be used or discarded.

HOW SUPPLIED SECTION.

16 HOW SUPPLIED/STORAGE AND HANDLING. How SuppliedELREXFIO(R) (elranatamab-bcmm) injection is sterile, preservative-free, clear to slightly opalescent, and colorless to pale brown liquid solution supplied as follows:oOne 76 mg/1.9 mL (40 mg/mL) single-dose vial in carton. NDC: 0069-4494-02oOne 44 mg/1.1 mL (40 mg/mL) single-dose vial in carton. NDC: 0069-2522-02ELREXFIO is supplied in single-dose glass vial sealed with rubber stopper (not made of natural rubber latex) and an aluminum seal with flip-off cap.Storage and HandlingStore refrigerated at C to C (36 to 46 F) in the original carton until time of use to protect from light.Do not freeze or shake the vial or carton.. oOne 76 mg/1.9 mL (40 mg/mL) single-dose vial in carton. NDC: 0069-4494-02. oOne 44 mg/1.1 mL (40 mg/mL) single-dose vial in carton. NDC: 0069-2522-02.

IMMUNOGENICITY.

12.6 Immunogenicity 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 studies described below with the incidence of anti-drug antibodies in other studies, including those of elranatamab-bcmm or of other elranatamab products.In the MagnetisMM-3 study, of the 168 participant who received recommended step-up and full dosage of ELREXFIO for up to 36 months and are evaluable for presence of ADA against elranatamab-bcmm, 9.5% (16/168) of patients tested positive for anti-elranatamab-bcmm-antibodies. Among the 16 patients who tested positive for ADAs, 56% (9/16) tested positive for neutralizing antibodies against elranatamab-bcmm. The effect of these antibodies on the pharmacokinetics, pharmacodynamics, safety, and/or effectiveness of ELREXFIO products is unknown.

INDICATIONS & USAGE SECTION.

1 INDICATIONS AND USAGE ELREXFIO 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 of clinical benefit in confirmatory trial(s).. ELREXFIO 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 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)Discuss the signs and symptoms associated with CRS, including fever, hypoxia, chills, hypotension, tachycardia, and elevated liver enzymes. Advise patients to immediately contact their healthcare provider if they experience any signs or symptoms of CRS. Advise patients that they will be hospitalized for 48 hours after administration of the first step-up dose, and for 24 hours after administration of the second step-up dose [see Dosage and Administration (2.5), Warnings and Precautions (5.1)].Neurologic Toxicity, Including Immune Effector Cell-associated Neurotoxicity Syndrome (ICANS)Discuss the signs and symptoms associated with neurologic toxicity, including ICANS, including headache, encephalopathy, motor dysfunction, sensory neuropathy, and Guillain-Barre Syndrome. 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 completing each of the step-up doses and the first treatment dose within the ELREXFIO step-up dosing schedule and in the event of new onset of any neurological toxicity symptoms until symptoms resolve [see Dosage and Administration (2.5), Warnings and Precautions (5.2)].ELREXFIO REMSELREXFIO is available only through restricted program called ELREXFIO REMS. Inform patients that they will be given an ELREXFIO Patient Wallet Card that they should carry with them at all times and show to all of their healthcare providers. This card describes signs and symptoms of CRS and neurologic toxicity, including ICANS which, if experienced, should prompt the patient to immediately seek medical attention [see Warnings and Precautions (5.3)].InfectionsDiscuss the signs and symptoms of infection [see Dosage and Administration (2.5), Warnings and Precautions (5.4)].NeutropeniaDiscuss the signs and symptoms associated with neutropenia and febrile neutropenia [see Dosage and Administration (2.5), Warnings and Precautions (5.5)].HepatotoxicityAdvise patients that liver enzyme 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 ELREXFIO 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 ELREXFIO and for months after the last dose [see Use in Specific Populations (8.2)].Manufactured by:Pfizer Inc.NY, NY 10001US License No. 2001 LAB-1518-4.0. Logo.

LACTATION SECTION.

8.2 Lactation Risk SummaryThere are no data on the presence of elranatamab-bcmm 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 ELREXFIO and for months after the last dose.

MECHANISM OF ACTION SECTION.

12.1 Mechanism of Action Elranatamab-bcmm is bispecific B-cell maturation antigen (BCMA)-directed T-cell engaging antibody that binds BCMA on plasma cells, plasmablasts, and multiple myeloma cells and CD3 on T-cells leading to cytolysis of the BCMA-expressing cells. Elranatamab-bcmm activated T-cells, caused proinflammatory cytokine release, and resulted in multiple myeloma cell lysis.

NONCLINICAL TOXICOLOGY SECTION.

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

PACKAGE LABEL.PRINCIPAL DISPLAY PANEL.

PRINCIPAL DISPLAY PANEL 44 mg/1.1 mL Vial DISPENSE THE ACCOMPANYINGMEDICATION GUIDE TO EACH PATIENTPROFESSIONAL SAMPLE NOT FOR SALENDC 63539-252-01Rx onlyELREXFIOTM (elranatamab-bcmm)INJECTION FOR SUBCUTANEOUS USE44 mg/1.1 mL (40 mg/mL)One SINGLE-DOSE VIALDISCARD UNUSED PORTION. Pfizer. PRINCIPAL DISPLAY PANEL 44 mg/1.1 mL Vial.

PEDIATRIC USE SECTION.

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

PHARMACODYNAMICS SECTION.

12.2 Pharmacodynamics Cytokine ConcentrationsTransient elevation of circulating cytokines IL-2, IL-6, IL-8, IL-10, TNF-, and IFN- was observed at dosage levels of 30 ug/kg (0.03 times the approved recommended dosage) and above. After administration of the approved recommended dosage of ELREXFIO, the highest elevation of cytokines was generally observed within 72 hours after first elranatamab-bcmm dose at 12 mg on Day 1, and generally returned to baseline prior to the administration of the first full dose 76 mg on Day 8.

PHARMACOKINETICS SECTION.

12.3 Pharmacokinetics Pharmacokinetic parameters are presented as geometric mean (coefficient of variation [CV]%) and are based upon subcutaneously administered unless otherwise specified.Elranatamab-bcmm exhibits dose proportional pharmacokinetics over dose range from to 76 mg (0.079 to times the approved recommended dosage). Elranatamab-bcmm maximum concentration [33.0 mcg/mL (46%)] is achieved at the end of weekly dosing regimen (i.e., at week 24 of 76 mg weekly dosing). Pharmacokinetic exposures are summarized for the recommended dosage of ELREXFIO in Table 10.Table 10. Pharmacokinetic Parameters of Elranatamab-bcmm in Subjects with Relapsed or Refractory Multiple MyelomaTimepointParametersCavg (mcg/mL)Cmax (mcg/mL)Ctrough (mcg/mL)First full 76 mg dose3.1 (94%)3.8 (94%)3.3 (102%)End of weekly dose (week 24)In patients who have achieved response. 32.0 (46%)33.0 (46%)30.5 (48%)Steady state (biweekly dosing) Steady state exposure of elranatamab biweekly dose is approximated at week 48. 17.7 (53%)19.5 (51%)15.1 (60%)Steady state (every weeks dosing) Steady state exposure of elranatamab once every weeks dose is approximated at week 72. 8.8 (58%)11.5 (54%)5.9 (78%)Absorption The mean bioavailability of elranatamab-bcmm was 56.2% when administered subcutaneously. The median (min, max) Tmax after elranatamab SC administration was (3 to 7) days.DistributionThe steady state volume of distribution of elranatamab-bcmm was 7.76 (33%).EliminationThe half-life of elranatamab-bcmm is 22 (64%) days at the 76 mg dosage, with clearance of 0.324 L/day (100%) following 24 weeks dosing. MetabolismElranatamab-bcmm is expected to be metabolized into small peptides by catabolic pathways.Specific PopulationsNo clinically significant differences in the pharmacokinetics of elranatamab-bcmm were observed based on age (36 to 89 years), sex, race (White, Asian, or Black), body weight (37 to 160 kg), mild or moderate renal impairment (estimated glomerular filtration rate [eGFR] by Modification of Diet in Renal Disease [MDRD] method: 30 to 89 mL/min), or mild hepatic impairment (total bilirubin to <=1.5 ULN or any AST greater than ULN).The effects of severe renal impairment (eGFR 15 to 29 mL/min), end-stage renal disease (eGFR <15 mL/min), or moderate to severe hepatic impairment (total bilirubin >1.5 times ULN and any AST) on the PK of elranatamab-bcmm are unknown.

PREGNANCY SECTION.

8.1 Pregnancy Risk Summary Based on the mechanism of action, ELREXFIO may cause fetal harm when administered to pregnant woman [see Clinical Pharmacology (12.1)]. There are no available data on the use of ELREXFIO in pregnant women to evaluate for drug associated risk. No animal reproductive or developmental toxicity studies have been conducted with ELREXFIO. Elranatamab-bcmm 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, elranatamab-bcmm can cause B-cell lymphocytopenia in infants exposed to elranatamab-bcmm in-utero. Human immunoglobulin (IgG) is known to cross the placenta after the first trimester of pregnancy; therefore, elranatamab-bcmm has the potential to be transmitted from the mother to the developing fetus. Advise women of the potential risk to the fetus.ELREXFIO is associated with hypogammaglobulinemia, therefore, assessment of immunoglobulin levels in newborns of mothers treated with ELREXFIO 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.

RECENT MAJOR CHANGES SECTION.

Dosage and Administration, Recommended Dosage (2.2)7/2025Dosage and Administration, Restarting ELREXFIO After Dosage Delay (2.4)7/2025Dosage and Administration, Preparation and Administration Instructions (2.6)7/2025.

SPL MEDGUIDE SECTION.

This Medication Guide has been approved by the U.S. Food and Drug Administration. Revised: Feb 2026MEDICATION GUIDEELREXFIO(R) (el-reks-fe-o)(elranatamab-bcmm) injection, for subcutaneous useWhat is the most important information should know about ELREXFIO ELREXFIO may cause serious side effects, including:oCytokine Release Syndrome (CRS). CRS is common during treatment with ELREXFIO and can also be serious, life-threatening, or can lead to death. Tell your healthcare provider or get medical help right away if you develop any signs or symptoms of CRS, including:ofever of 100.4 (38 C) or higherotrouble breathingochillsodizziness or light-headednessofast heartbeatoheadacheoincreased liver enzymes in your blood. See What are the possible side effects of ELREXFIO for more information about the signs and symptoms of liver problems. Due to the risk of CRS, you will receive ELREXFIO on step-up dosing schedule and should be hospitalized for 48 hours after the first step-up dose and for 24 hours after the second step-up dose of ELREXFIO.oDuring the step-up dosing schedule:for your first dose, you will receive smaller step-up dose of ELREXFIO on Day of your treatmentfor your second dose, you will receive larger step-up dose of ELREXFIO, which is usually given on Day of your treatmentfor your third dose, you will receive the first full treatment dose of ELREXFIO, which is usually given on Day of your treatmentoIf your dose of ELREXFIO is delayed for any reason, you may need to repeat the step-up dosing schedule. oBefore each step-up dose and the first full treatment dose of ELREXFIO, you will receive medicines to help reduce your risk of CRS. Your healthcare provider will decide if you need to receive medicines to help reduce your risk of CRS with future doses.oSee How will receive ELREXFIO for more information about how you will receive ELREXFIO. oNeurologic problems. ELREXFIO 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:oheadacheoagitation, trouble staying awake, confusion or disorientation, seeing or hearing things that are not real (hallucinations)otrouble speaking, thinking, remembering things, paying attention, or understanding thingsoproblems walking, muscle weakness, shaking (tremors), loss of balance, or muscle spasmsonumbness and tingling (feeling like pins and needles)oburning, throbbing, or stabbing painochanges in your handwritingoELREXFIO is available only through the ELREXFIO Risk Evaluation and Mitigation Strategy (REMS) due to the risk of CRS and neurologic problems. You will receive an ELREXFIO Patient Wallet Card from your healthcare provider. Carry the ELREXFIO Patient Wallet Card with you at all times and show it to all of your healthcare providers. The ELREXFIO Patient Wallet Card lists symptoms of CRS and neurologic problems. Get medical help right away if you develop any of the symptoms listed on the ELREXFIO 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 ELREXFIO, as well as other side effects, and will treat you if needed. Your healthcare provider may temporarily stop or completely stop your treatment with ELREXFIO if you develop CRS, neurologic problems, or any other side effects that are severe.If you have any questions about ELREXFIO, ask your healthcare provider.See What are possible side effects of ELREXFIO for more information about side effects.What is ELREXFIOELREXFIO is prescription medicine used to treat adults with multiple myeloma who:ohave already received at least treatment regimens, including proteasome inhibitor, an immunomodulatory agent and an anti-CD38 monoclonal antibody to treat their multiple myeloma, andotheir cancer has come back or did not respond to prior treatment.It is not known if ELREXFIO is safe and effective in children.Before receiving ELREXFIO, tell your healthcare provider about all of your medical conditions, including if you:ohave an infection.oare pregnant or plan to become pregnant. ELREXFIO may harm your unborn baby.Females who are able to become pregnant:oYour healthcare provider should do pregnancy test before you start treatment with ELREXFIO.oYou should use effective birth control (contraception) during treatment and for months after your last dose of ELREXFIO.oTell your healthcare provider right away if you become pregnant or think that you may be pregnant during treatment with ELREXFIO.oare breastfeeding or plan to breastfeed. It is not known if ELREXFIO passes into your breast milk. Do not breastfeed during treatment and for months after your last dose of ELREXFIO.Tell your healthcare provider about all the medicines you take, including prescription and over-the-counter medicines, vitamins, and herbal supplements.How will receive ELREXFIOoELREXFIO will be given to you by your healthcare provider as an injection under your skin (subcutaneous injection), usually in your stomach-area (abdomen). Your thigh or another area of your body may also be used.oSee What is the most important information should know about ELREXFIO for more information about how you will receive ELREXFIO.oAfter you receive your first full treatment dose, ELREXFIO is usually given time each week through Week 24.oStarting on Week 25, your future doses will usually be given time every weeks.oStarting on Week 49, your future doses will usually be given time every weeks.oYour healthcare provider will decide the time between doses and how long you will receive treatment with ELREXFIO.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 ELREXFIO.What should avoid while receiving ELREXFIODo not drive, operate heavy or potentially dangerous machinery, or do other dangerous activities during treatment with ELREXFIO:ofor 48 hours after completing each of the doses of ELREXFIO that are part of the step-up dosing schedule and your first full treatment dose, and oat any time during treatment with ELREXFIO if you develop any new neurologic symptoms such as dizziness, confusion, shaking (tremors), sleepiness, or any other symptom that impairs consciousness, until the symptoms go away.See What is the most important information should know about ELREXFIO for more information about signs and symptoms of neurologic problems.What are the possible side effects of ELREXFIOELREXFIO may cause serious side effects, including:oSee What is the most important information should know about ELREXFIOoInfections. Upper respiratory tract infections and pneumonia are common during treatment with ELREXFIO. ELREXFIO can cause bacterial and viral infections that are severe, life-threatening, or that may lead to death.oYour healthcare provider may prescribe medicines for you to help prevent infections and treat you as needed if you develop an infection during treatment with ELREXFIO.oTell your healthcare provider right away if you develop any signs or symptoms of an infection during treatment with ELREXFIO, including: fever of 100.4 (38 C) or higherchillscoughshortness of breathchest painsore throatpain during urinationfeeling weak or generally unwelloDecreased white blood cell counts. Decreased white blood cell counts are common during treatment with ELREXFIO 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 treat you as needed.oLiver problems. ELREXFIO can cause increased liver enzymes and bilirubin in your blood. These increases can happen with or without you also having CRS. Tell your healthcare provider if you develop any of the following signs or symptoms of liver problems:otirednessoloss of appetiteopain in your right upper stomach-area (abdomen)odark urineoyellowing of your skin or the white part of your eyesYour healthcare provider will check your blood and monitor you for signs and symptoms of these serious side effects before you start and during treatment with ELREXFIO and may temporarily or completely stop treatment with ELREXFIO if you develop certain side effects.The most common side effects of ELREXFIO include:otirednessoinjection site reaction, such as redness, itching, pain, bruising, rash, swelling, tendernessodiarrheaomuscle and bone painodecreased appetiteorashocoughonauseaofeverThe most common severe abnormal blood test results with ELREXFIO include decreased white blood cells, red blood cells, and platelets.These are not all of the possible side effects of ELREXFIO.Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088.General information about the safe and effective use of ELREXFIO.Medicines are sometimes prescribed for purposes other than those listed in Medication Guide. You can ask your pharmacist or healthcare provider for more information about ELREXFIO that is written for health professionals.What are the ingredients in ELREXFIOActive ingredient: elranatamab-bcmmInactive ingredients: edetate disodium, histidine, L-histidine hydrochloride monohydrate, polysorbate 80, sucrose, and Water for InjectionManufactured by: Pfizer Inc., NY, NY 10001US License No. 2001LAB-1551-3.0For more information on ELREXFIO, go to www.ELREXFIO.com For more information on Pfizer, go to www.Pfizer.com or call 1-800-438-1985. oCytokine Release Syndrome (CRS). CRS is common during treatment with ELREXFIO and can also be serious, life-threatening, or can lead to death. Tell your healthcare provider or get medical help right away if you develop any signs or symptoms of CRS, including:. ofever of 100.4 (38 C) or higher. otrouble breathing. ochills. odizziness or light-headedness. ofast heartbeat. oheadache. oincreased liver enzymes in your blood. See What are the possible side effects of ELREXFIO for more information about the signs and symptoms of liver problems.. Due to the risk of CRS, you will receive ELREXFIO on step-up dosing schedule and should be hospitalized for 48 hours after the first step-up dose and for 24 hours after the second step-up dose of ELREXFIO.oDuring the step-up dosing schedule:for your first dose, you will receive smaller step-up dose of ELREXFIO on Day of your treatmentfor your second dose, you will receive larger step-up dose of ELREXFIO, which is usually given on Day of your treatmentfor your third dose, you will receive the first full treatment dose of ELREXFIO, which is usually given on Day of your treatmentoIf your dose of ELREXFIO is delayed for any reason, you may need to repeat the step-up dosing schedule. oBefore each step-up dose and the first full treatment dose of ELREXFIO, you will receive medicines to help reduce your risk of CRS. Your healthcare provider will decide if you need to receive medicines to help reduce your risk of CRS with future doses.oSee How will receive ELREXFIO for more information about how you will receive ELREXFIO. oDuring the step-up dosing schedule:for your first dose, you will receive smaller step-up dose of ELREXFIO on Day of your treatmentfor your second dose, you will receive larger step-up dose of ELREXFIO, which is usually given on Day of your treatmentfor your third dose, you will receive the first full treatment dose of ELREXFIO, which is usually given on Day of your treatment. for your first dose, you will receive smaller step-up dose of ELREXFIO on Day of your treatment. for your second dose, you will receive larger step-up dose of ELREXFIO, which is usually given on Day of your treatment. for your third dose, you will receive the first full treatment dose of ELREXFIO, which is usually given on Day of your treatment. oIf your dose of ELREXFIO is delayed for any reason, you may need to repeat the step-up dosing schedule. oBefore each step-up dose and the first full treatment dose of ELREXFIO, you will receive medicines to help reduce your risk of CRS. Your healthcare provider will decide if you need to receive medicines to help reduce your risk of CRS with future doses.. oSee How will receive ELREXFIO for more information about how you will receive ELREXFIO.. oNeurologic problems. ELREXFIO 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:. oheadache. oagitation, trouble staying awake, confusion or disorientation, seeing or hearing things that are not real (hallucinations). otrouble speaking, thinking, remembering things, paying attention, or understanding things. oproblems walking, muscle weakness, shaking (tremors), loss of balance, or muscle spasms. onumbness and tingling (feeling like pins and needles). oburning, throbbing, or stabbing pain. ochanges in your handwriting. oELREXFIO is available only through the ELREXFIO Risk Evaluation and Mitigation Strategy (REMS) due to the risk of CRS and neurologic problems. You will receive an ELREXFIO Patient Wallet Card from your healthcare provider. Carry the ELREXFIO Patient Wallet Card with you at all times and show it to all of your healthcare providers. The ELREXFIO Patient Wallet Card lists symptoms of CRS and neurologic problems. Get medical help right away if you develop any of the symptoms listed on the ELREXFIO Patient Wallet Card. You may need to be treated in hospital.. ohave already received at least treatment regimens, including proteasome inhibitor, an immunomodulatory agent and an anti-CD38 monoclonal antibody to treat their multiple myeloma, and. otheir cancer has come back or did not respond to prior treatment.. ohave an infection.. oare pregnant or plan to become pregnant. ELREXFIO may harm your unborn baby.Females who are able to become pregnant:oYour healthcare provider should do pregnancy test before you start treatment with ELREXFIO.oYou should use effective birth control (contraception) during treatment and for months after your last dose of ELREXFIO.oTell your healthcare provider right away if you become pregnant or think that you may be pregnant during treatment with ELREXFIO.. oYour healthcare provider should do pregnancy test before you start treatment with ELREXFIO.. oYou should use effective birth control (contraception) during treatment and for months after your last dose of ELREXFIO.. oTell your healthcare provider right away if you become pregnant or think that you may be pregnant during treatment with ELREXFIO.. oare breastfeeding or plan to breastfeed. It is not known if ELREXFIO passes into your breast milk. Do not breastfeed during treatment and for months after your last dose of ELREXFIO.. oELREXFIO will be given to you by your healthcare provider as an injection under your skin (subcutaneous injection), usually in your stomach-area (abdomen). Your thigh or another area of your body may also be used.. oSee What is the most important information should know about ELREXFIO for more information about how you will receive ELREXFIO.. oAfter you receive your first full treatment dose, ELREXFIO is usually given time each week through Week 24.. oStarting on Week 25, your future doses will usually be given time every weeks.. oStarting on Week 49, your future doses will usually be given time every weeks.. oYour healthcare provider will decide the time between doses and how long you will receive treatment with ELREXFIO.. ofor 48 hours after completing each of the doses of ELREXFIO that are part of the step-up dosing schedule and your first full treatment dose, and oat any time during treatment with ELREXFIO if you develop any new neurologic symptoms such as dizziness, confusion, shaking (tremors), sleepiness, or any other symptom that impairs consciousness, until the symptoms go away.. oSee What is the most important information should know about ELREXFIO. oInfections. Upper respiratory tract infections and pneumonia are common during treatment with ELREXFIO. ELREXFIO can cause bacterial and viral infections that are severe, life-threatening, or that may lead to death.oYour healthcare provider may prescribe medicines for you to help prevent infections and treat you as needed if you develop an infection during treatment with ELREXFIO.oTell your healthcare provider right away if you develop any signs or symptoms of an infection during treatment with ELREXFIO, including: oYour healthcare provider may prescribe medicines for you to help prevent infections and treat you as needed if you develop an infection during treatment with ELREXFIO.. oTell your healthcare provider right away if you develop any signs or symptoms of an infection during treatment with ELREXFIO, including:. fever of 100.4 (38 C) or higher. chills. cough. shortness of breath. chest pain. sore throat. pain during urination. feeling weak or generally unwell. oDecreased white blood cell counts. Decreased white blood cell counts are common during treatment with ELREXFIO 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 treat you as needed.. oLiver problems. ELREXFIO can cause increased liver enzymes and bilirubin in your blood. These increases can happen with or without you also having CRS. Tell your healthcare provider if you develop any of the following signs or symptoms of liver problems:. otiredness. oloss of appetite. opain in your right upper stomach-area (abdomen). odark urine. oyellowing of your skin or the white part of your eyes. otiredness. oinjection site reaction, such as redness, itching, pain, bruising, rash, swelling, tenderness. odiarrhea. omuscle and bone pain. odecreased appetite. orash. ocough. onausea. ofever. Logo.

SPL UNCLASSIFIED SECTION.

2.1 Important Dosing Information Administer ELREXFIO subcutaneously according to the step-up dosing schedule to reduce the incidence and severity of cytokine release syndrome (CRS).Administer pre-treatment medications prior to each dose in the ELREXFIO step-up dosing schedule, which includes step-up dose 1, step-up dose 2, and the first treatment dose as recommended [see Dosage and Administration (2.2, 2.3)].ELREXFIO should only be administered by qualified healthcare professional with appropriate medical support to manage severe reactions such as CRS and neurologic toxicity, including ICANS [see Warnings and Precautions (5.1, 5.2)].Due to the risk of CRS, patients should be hospitalized for 48 hours after administration of the first step-up dose, and for 24 hours after administration of the second step-up dose.

USE IN SPECIFIC POPULATIONS SECTION.

8 USE IN SPECIFIC POPULATIONS Lactation: Advise not to breastfeed. (8.2). 8.1 Pregnancy Risk Summary Based on the mechanism of action, ELREXFIO may cause fetal harm when administered to pregnant woman [see Clinical Pharmacology (12.1)]. There are no available data on the use of ELREXFIO in pregnant women to evaluate for drug associated risk. No animal reproductive or developmental toxicity studies have been conducted with ELREXFIO. Elranatamab-bcmm 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, elranatamab-bcmm can cause B-cell lymphocytopenia in infants exposed to elranatamab-bcmm in-utero. Human immunoglobulin (IgG) is known to cross the placenta after the first trimester of pregnancy; therefore, elranatamab-bcmm has the potential to be transmitted from the mother to the developing fetus. Advise women of the potential risk to the fetus.ELREXFIO is associated with hypogammaglobulinemia, therefore, assessment of immunoglobulin levels in newborns of mothers treated with ELREXFIO 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 elranatamab-bcmm 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 ELREXFIO and for months after the last dose.. 8.3 Females and Males of Reproductive Potential ELREXFIO 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 ELREXFIO.Contraception Females Advise females of reproductive potential to use effective contraception during treatment and for months after the last dose of ELREXFIO.. 8.4 Pediatric Use The safety and effectiveness of ELREXFIO in pediatric patients have not been established.. 8.5 Geriatric Use Of the 183 patients with relapsed or refractory multiple myeloma treated with ELREXFIO in MagnetisMM-3 at the recommended dosage, 62% were 65 years of age or older, and 19% were 75 years of age or older. No overall differences in safety or effectiveness were observed in patients 65-74 years of age compared to younger patients. Clinical studies did not include sufficient numbers of patients 75 years of age or older to determine whether they respond differently from younger patients.

WARNINGS AND PRECAUTIONS SECTION.

5 WARNINGS AND PRECAUTIONS oInfections: Can cause severe, life-threatening, or fatal infections. Monitor patients for signs and symptoms of infection and treat appropriately. Do not initiate treatment in patients with active infections. (5.4)oNeutropenia: Monitor complete blood cell counts at baseline and periodically during treatment. (5.5)oHepatotoxicity: Can cause elevated ALT, AST, and bilirubin. Monitor liver enzymes and bilirubin at baseline and during treatment as clinically indicated. (5.6)oEmbryo-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). oInfections: Can cause severe, life-threatening, or fatal infections. Monitor patients for signs and symptoms of infection and treat appropriately. Do not initiate treatment in patients with active infections. (5.4). oNeutropenia: Monitor complete blood cell counts at baseline and periodically during treatment. (5.5). oHepatotoxicity: Can cause elevated ALT, AST, and bilirubin. Monitor liver enzymes and bilirubin at baseline and during treatment as clinically indicated. (5.6). oEmbryo-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). 5.1 Cytokine Release Syndrome (CRS) ELREXFIO can cause CRS, including life-threatening or fatal reactions [see Adverse Reactions (6.1)].In the clinical trial, CRS occurred in 58% of patients who received ELREXFIO at the recommended dosing schedule [see Dosage and Administration (2.2)], with Grade CRS in 44% of patients, Grade CRS in 14% of patients, and Grade CRS in 0.5% of patients. Recurrent CRS occurred in 13% of patients. Most patients experienced CRS after the first step-up dose (43%) or the second step-up dose (19%), with 7% of patients having CRS after the first treatment dose and 1.6% of patients after subsequent dose. The median time to onset of CRS was (range: to 9) days after the most recent dose, with median duration of (range: to 19) days.Clinical signs and symptoms of CRS may include, but are not limited to, fever, hypoxia, chills, hypotension, tachycardia, headache, and elevated liver enzymes.Initiate therapy according to the ELREXFIO step-up dosing schedule to reduce risk of CRS and monitor patients following administration of ELREXFIO accordingly [see Dosage and Administration (2.2, 2.5)]. Administer pre-treatment medications prior to each dose in the step-up dosing schedule to reduce risk of CRS [see Dosage and Administration (2.3)].Counsel patients to seek medical attention should signs or symptoms of CRS occur. At the first sign of CRS, evaluate patients immediately for hospitalization. Manage CRS according to the recommendations and consider further management per current practice guidelines. Withhold or permanently discontinue ELREXFIO based on severity [see Dosage and Administration (2.5)].ELREXFIO is available only through restricted program under REMS [see Warnings and Precautions (5.3)].. 5.2 Neurologic Toxicity, Including Immune Effector Cell-Associated Neurotoxicity Syndrome (ICANS) ELREXFIO can cause serious or life-threatening neurologic toxicity, including ICANS [see Adverse Reactions (6.1)].In the clinical trial, neurologic toxicity occurred in 59% of patients who received ELREXFIO at the recommended dosing schedule [see Dosage and Administration (2.2)], with Grade or neurologic toxicity occurring in 7% of patients. Neurologic toxicities included headache (18%), encephalopathy (15%), motor dysfunction (13%), sensory neuropathy (13%), and Guillain-Barre Syndrome (0.5%).In the clinical trial, ICANS occurred in 3.3% of patients who received ELREXFIO at the recommended dosing schedule [see Dosage and Administration (2.2)]. Most patients had ICANS after the first step-up dose (2.7%), (0.5%) patient had ICANS after the second step-up dose and (0.5%) patient had ICANS after subsequent dose(s). Recurrent ICANS occurred in 1.1% of patients. The median time to onset was (range: to 4) days after the most recent dose, with median duration of (range: to 18) days. The most frequent clinical manifestations of ICANS included depressed level of consciousness and Grade or Grade Immune Effector Cell-Associated Encephalopathy (ICE) scores. The onset of ICANS can be concurrent with CRS, following resolution of CRS, or in the absence of CRS.Counsel patients to seek medical attention should signs or symptoms of neurologic toxicity occur. Monitor patients for signs and symptoms of neurologic toxicities during treatment with ELREXFIO. At the first sign of neurologic toxicity, including ICANS, evaluate and treat patients immediately based on severity. Withhold or permanently discontinue ELREXFIO based on severity per recommendations [see Dosage and Administration (2.5)] and consider further management per current practice guidelines.Due to the potential for neurologic toxicity including ICANS, patients receiving ELREXFIO are at risk of depressed level of consciousness. Advise patients not to drive or operate heavy or potentially dangerous machinery for 48 hours after completing each of the step-up doses and the first treatment dose within the ELREXFIO step-up dosing schedule and in the event of new onset of any neurological toxicity symptoms until symptoms resolve [see Dosage and Administration (2.2)].ELREXFIO is available only through restricted program under REMS [see Warnings and Precautions (5.3)].. 5.3 ELREXFIO REMS ELREXFIO is available only through restricted program under REMS called the ELREXFIO REMS because of the risks of CRS and neurologic toxicity, including ICANS [see Warnings and Precautions (5.1, 5.2)].Notable requirements of the ELREXFIO REMS include the following:oPrescribers must be certified with the program by enrolling and completing training.oPrescribers must counsel patients receiving ELREXFIO about the risk of CRS and neurologic toxicity, including ICANS, and provide patients with ELREXFIO Patient Wallet Card.oPharmacies and healthcare settings that dispense ELREXFIO must be certified with the ELREXFIO REMS program and must verify prescribers are certified through the ELREXFIO REMS program.oWholesalers and distributers must only distribute ELREXFIO to certified pharmacies or healthcare settings.Further information about the ELREXFIO REMS program is available at www.ELREXFIOREMS.com or by telephone at 1-844-923-7845.. oPrescribers must be certified with the program by enrolling and completing training.. oPrescribers must counsel patients receiving ELREXFIO about the risk of CRS and neurologic toxicity, including ICANS, and provide patients with ELREXFIO Patient Wallet Card.. oPharmacies and healthcare settings that dispense ELREXFIO must be certified with the ELREXFIO REMS program and must verify prescribers are certified through the ELREXFIO REMS program.. oWholesalers and distributers must only distribute ELREXFIO to certified pharmacies or healthcare settings.. 5.4 Infections ELREXFIO can cause severe, life-threatening, or fatal infections. In the clinical trial, in patients who received ELREXFIO according to the recommended dosing schedule, serious infections, including opportunistic infections, occurred in 42% of patients, with Grade or infections in 31%, and fatal infections in 7%. The most common serious infections reported (>=5%) were pneumonia and sepsis [see Adverse Reactions (6.1)].Do not initiate treatment with ELREXFIO in patients with active infections. Monitor patients for signs and symptoms of infection prior to and during treatment with ELREXFIO and treat appropriately. Withhold or permanently discontinue ELREXFIO based on severity [see Dosage and Administration (2.5)]. Administer prophylactic antimicrobial and anti-viral medications according to current practice guidelines. Consider treatment with subcutaneous or intravenous immunoglobulin (IVIG) as appropriate.. 5.5 Neutropenia ELREXFIO can cause neutropenia and febrile neutropenia. In patients who received ELREXFIO at the recommended dose in the clinical trial, decreased neutrophils occurred in 62% of patients, with Grade or decreased neutrophils in 51%. Febrile neutropenia occurred in 2.2% of patients [see Adverse Reactions (6.1)].Monitor complete blood cell counts at baseline and periodically during treatment. Provide supportive care according to current practice guidelines. Monitor patients with neutropenia for signs of infection. Withhold ELREXFIO based on severity [see Dosage and Administration (2.5)].. 5.6 Hepatotoxicity ELREXFIO can cause hepatotoxicity. In the clinical trial, elevated ALT occurred in 36% of patients, with Grade or ALT elevation occurring in 3.8%; elevated AST occurred in 40% of patients, with Grade or AST elevation occurring in 6%. Grade or total bilirubin elevations occurred in 0.5% 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 ELREXFIO or consider permanent discontinuation of ELREXFIO based on severity [see Dosage and Administration (2.5)].. 5.7 Embryo-Fetal Toxicity Based on its mechanism of action, ELREXFIO 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 ELREXFIO and for months after the last dose [see Use in Specific Populations (8.1, 8.3)].