REMS: FDA approved a REMS for elranatamab-bcmm to ensure that the benefits outweigh the risks. The REMS may apply to one or more preparations of elranatamab-bcmm and consists of the following: communication plan, elements to assure safe use, and implementation system. See the FDA REMS page for specific information [Web] |
Elranatamab-bcmm, a bispecific B-cell maturation antigen (BCMA)-directed CD3 T-cell engager, is an antineoplastic agent.1
Elranatamab-bcmm is used for the treatment of relapsed or refractory multiple myeloma in adults who have received ≥4 prior lines of therapy including a proteasome inhibitor, an immunomodulatory agent, and an anti-CD38 monoclonal antibody.1 Elranatamab-bcmm has been designated an orphan drug by FDA for the treatment of this cancer.2
Elranatamab-bcmm was approved under accelerated approval based on response rate and durability of response.1 Continued approval for this indication may be contingent upon verification of clinical benefit in a confirmatory trial(s).1
The current indication for elranatamab-bcmm is based principally on the results of an open-label, single-arm, multicenter clinical trial (MagnetisMM-3).1, 3 Enrolled patients were ≥18 years of age with refractory or relapsed multiple myeloma and measurable disease;3 the disease had to be refractory to ≥1 proteasome inhibitor, 1 immunomodulatory agent, and 1 anti-CD38 monoclonal antibody.1 Patients included in the study also had an Eastern Cooperative Oncology Group performance status ≤2; adequate bone marrow, hepatic and renal function; and left ventricular ejection fraction ≥40%.1 Patients who had a stem cell transplant ≤12 weeks before enrollment or active infection were excluded.1 Patients received subcutaneous elranatamab-bcmm with step-up dosing: 12 mg on day 1, 32 mg on day 4, and 76 mg (treatment dose) on day 8 and once weekly thereafter.1 At 24 weeks, the dosing interval was changed to every 2 weeks for patients with a partial response or better persisting for ≥2 months based on International Myeloma Working Group (IMWG) criteria.1 Efficacy was based on objective response rate (partial response or better) and duration of response as assessed by blinded independent review using IMWG criteria.1, 3
The study included 2 patient cohorts.1 Cohort A was the pivotal cohort which included 123 patients naïve to prior treatment with B-cell maturation antigen (BCMA)-directed therapy; these patients received a median of 5 lines (range 2-22) of prior therapy.1 Cohort B included 64 patients with prior BCMA-directed antibody drug conjugate (ADC) or chimeric antigen receptor (CAR) T-cell therapy.1 The efficacy population included 97 patients naïve to BCMA-directed therapy who received ≥4 prior lines of therapy.1 In the efficacy population, the median age was 69 years (range 46-89); 40% of the patients were female, 59.8% were white, 13.4% were Asian, 7.2% were Latino/Hispanic, and 5.2% were Black.1 Stage I, stage II, or stage III disease (based on the Revised International Staging System) was present in 20.6, 53.6, or 17.5% of patients, respectively.1 The median time since initial diagnosis of multiple myeloma to enrollment was 79.6 months (range 18-228); 96.9% of patients had triple-class refractory disease and 94.8% were refractory to their last line of therapy.1
The objective response rate in the efficacy population was 57.7%; a complete or better response, a very good partial response, and a partial response was observed in 25.8, 25.8, and 6.2% of patients, respectively.1 The median time to first response was 1.22 months (range 0.9-6.5).1 The median duration of response was not reached at the time of the analysis.1
Patients in cohort B received a median of 8 lines of prior therapy (range 4-19); 73 or 32% received prior BCMA-directed ADC or CAR T-cell therapy, respectively.1 The objective response rate among patients was 33.3%.1 The median duration of response was not reached after a median follow-up of 10.2 months among responders.1
The American Society of Clinical Oncology (ASCO) and Ontario Health (Cancer Care Ontario) published evidence-based recommendations for the treatment of multiple myeloma, including patients with relapsed or refractory disease.4 For the treatment of relapsed or refractory disease, the guideline recommends triplet therapy or T-cell redirecting therapies for eligible patients.4 Patients should be offered treatment regimens that include different agents from those in prior therapies whenever possible.4 The bispecific antibodies, including elranatamab, should be offered to eligible patients (including older and frail patients) where other options are not possible or exhausted.4
Dispensing and Administration Precautions
Elranatamab-bcmm is administered by subcutaneous administration by a healthcare professional; only qualified healthcare professionals with sufficient and appropriate medical support to manage severe reactions such as CRS and neurologic toxicity (including ICANS) should administer elranatamab-bcmm.1
Administer the drug according to the step-up dosing schedule to reduce the incidence and severity of CRS.1 Administer the following pretreatment medications approximately 1 hour before the first 3 doses in the elranatamab-bcmm step-up dosing schedule, which includes step-up dose 1, step-up dose 2, and the first treatment dose, to reduce the risk of CRS: acetaminophen (or equivalent) 650 mg orally, dexamethasone (or equivalent) 20 mg orally or IV, and diphenhydramine (or equivalent) 25 mg orally.1 Due to the risk of CRS, hospitalize patients for 48 hours after administration of the first step-up dose, and for 24 hours after the second step-up dose.1
Elranatamab-bcmm is available as a ready-to-use solution supplied in a single-dose vial containing 76 mg/1.9 mL (40 mg/mL) or 44 mg/1.1 mL (40 mg/mL).1 The vials do not contain any preservatives and are for one-time use in a single patient.1 Use aseptic technique for preparation and administration.1 Dilution is not required prior to administration.1 The injection volumes are as follows: 0.3 mL for a total dose of 12 mg, 0.8 mL for a total dose of 32 mg, and 1.9 mL for a total dose of 76 mg.1
Store elranatamab-bcmm under refrigeration at 2-8°C in the original carton to protect from light; do not freeze or shake.1 To prepare, remove the appropriate strength vial from the refrigerator and allow to equilibrate to ambient temperature (15-30°C); do not warm the vial in any other manner.1 Once equilibrated, withdraw the required injection volume from the vial into an appropriately sized syringe with stainless steel injection needles (30G or wider) and polypropylene or polycarbonate syringe material.1 If the prepared dose syringe is not used immediately, store the syringe between 2-8°C for a maximum of 72 hours or between 8-25°C for a maximum of 24 hours.1 Once removed from refrigeration, the prepared syringe must be used or discarded.1
Prior to administration, inspect the drug visually.1 The solution should be colorless to pale brown; do not use if particulate matter or discoloration is observed.1 The preferred injection site is the abdomen; the drug may also be injected into subcutaneous tissue at other sites (e.g., thigh).1 Do not inject into tattoos, scars, or areas where the skin may be red, bruised, tender, hard, or not intact.1
Relapsed or Refractory Multiple Myeloma
The recommended dosing schedule for elranatamab is provided in Table 1.1
For patients who received ≥24 weeks of treatment with elranatamab-bcmm, achieved a response (partial response or better), and maintained this response for≥2 months, the dose interval should transition to an every-2-week schedule.1
For patients who received ≥24 weeks of treatment with elranatamab-bcmm at the every-2-week schedule and maintained response, the dose interval should transition to an every-4-week schedule.1
Continue treatment until disease progression or unacceptable toxicity occurs.1
Administer pretreatment medications prior to each dose of elranatamab-bcmm in the step-up dosing schedule, which includes step-up dose 1, step-up dose 2, and the first treatment dose.1
Dosing Schedule | Day | Dose |
|---|---|---|
Step-up dosing schedule | Day 1 | Step-up dose 1: 12 mg |
Step-up dosing schedule | Day 4 (maintain a minimum of 2 days between step-up dose 1 and step-up dose 2) | Step-up dose 2: 32 mg |
Step-up dosing schedule | Day 8 (maintain a minimum of 3 days between step-up dose 2 and the first treatment dose) | First treatment dose: 76 mg |
Weekly dosing schedule | One week after first treatment dose and weekly thereafter through week 24 (maintain a minimum of 6 days between treatment doses) | Subsequent treatment doses: 76 mg |
Biweekly (every 2 weeks) dosing schedule -responders only week 25 onward | Week 25 and every 2 weeks thereafter through week 48 (maintain a minimum of 6 days between treatment doses) | Subsequent treatment doses:76 mg |
Every 4 week dosing schedule - in patients who have maintained response following 24 weeks of treatment at the biweekly dosing schedule | Week 49 and every 4 weeks thereafter (maintain a minimum of 6 days between treatment doses) | Subsequent treatment doses: 76 mg |
Dosage Interruption for Toxicity
Dosage delays may be required to manage toxicities of elranatamab-bcmm.1
If a dose is delayed, restart therapy based on recommendations in Table 2 and resume the dosing schedule accordingly.1 Administer premedications as indicated in Table 2.1
Last Dose Administered | Time Since Last Dose Administered | Recommendations |
|---|---|---|
Step-up dose 1 (12 mg) | 2 weeks or less (≤14 days) | Restart at step-up dose 2 (32 mg). Administer pre-medications prior to the dose. If tolerated, increase to 76 mg 4 days later. |
Step-up dose 1 (12 mg) | Greater than 2 weeks (>14 days) | Restart at step-up dose 1 (12 mg). Administer pre-medications prior to the dose. |
Step-up dose 2 (32 mg) | 2 weeks or less (≤14 days) | Restart at 76 mg. Administer pre-medications prior to the dose. |
Step-up dose 2 (32 mg) | Greater than 2 weeks to less than or equal to 4 weeks (15 days to ≤28 days) | Restart at step-up dose 2 (32 mg). Administer pre-medications prior to the dose. If tolerated, increase to 76 mg 1 week later. |
Step-up dose 2 (32 mg) | Greater than 4 weeks (>28 days) | Restart at step-up dose 1 (12 mg). Administer pre-medications prior to the dose. |
Any weekly treatment dose (76 mg) | 8 weeks or less (≤56 days) | Restart at 76 mg. |
Any treatment dose (76 mg) | Greater than 8 weeks to less than or equal to 12 weeks (57 days to ≤84 days)a | Restart at step-up dose 2 (32 mg). Administer pre-medications prior to the dose. If tolerated, increase to 76 mg 1 week later. |
Any treatment dose (76 mg) | Greater than 12 weeks (>84 days)a | Restart at step-up dose 1 (12 mg). Administer pre-medications prior to the dose. |
Any biweekly or every-4-week treatment dose (76 mg) | 12 weeks or less (≤84 days) | Restart at 76 mg. |
Any biweekly or every-4-week treatment dose (76 mg) | Greater than 12 weeks (>84 days)a | Restart at step-up dose 1 (12 mg). Administer pre-medications prior to the dose. |
aConsider the risks and benefits of restarting elranatamab in patients who require a dosage delay of >56 days due to an adverse reaction.
Dosage Modification for Toxicity
Dosage reductions of elranatamab-bcmm are not recommended.1
Dosage delays may be required to manage toxicities related to elranatamab.1 Refer to Table 2 for recommendations on restarting after a dose delay.1
If CRS is suspected, withhold elranatamab until CRS resolves.1 Manage CRS according to the recommendations in Table 3 and consider further management in accordance with current practice guidelines.1 Administer supportive therapy for CRS, which may include intensive care for severe or life-threatening CRS.1 Consider laboratory testing to monitor for disseminated intravascular coagulation, hematology parameters, as well as pulmonary, cardiac, renal, and hepatic function.1
Grade a | Presenting Symptoms | Recommendations |
|---|---|---|
Grade 1 | Temperature ≥38°Cb | Withhold elranatamab until CRS resolvesd Administer pretreatment medications prior to next dose |
Grade 2 | Temperature ≥38°C with either:
| Withhold elranatamab until CRS resolvesd Monitor daily for 48 hours following the next dose Instruct patients to remain within proximity of a healthcare facility, and consider hospitalization Administer pretreatment medications prior to next dose |
Grade 3 (first occurrence) | Temperature ≥38°C with either:
| Withhold elranatamab until CRS resolvesd Provide supportive therapy, which may include intensive care Hospitalize patients for 48 hours following the next dose of elranatamab-bcmm Administer pretreatment medications prior to next dose |
Grade 3 (recurrent) | Temperature ≥38°C with either:
| Permanently discontinue elranatamab Provide supportive therapy, which may include intensive care |
Grade 4 | Temperature ≥38°C with either:
| Permanently discontinue elranatamab Provide supportive therapy, which may include intensive care |
aBased on American Society for Transplantation and Cellular Therapy (ASTCT) 2019 grading criteria for CRS.
bAttributed 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.
cLow-flow nasal cannula is ≤6 L/min; high-flow nasal cannula is >6 L/min.
dRefer to Table 2 for recommendations on restarting elranatamab-bcmm after a dose delay.
Refer to Tables 4 and 5 for the management of ICANS and neurologic toxicity (excluding ICANS), respectively.1
At the first sign of neurologic toxicity (including ICANS), withhold elranatamab and consider neurology evaluation.1 Rule out other causes of neurologic symptoms.1 Provide supportive therapy, which may include intensive care, for severe or life-threatening neurologic toxicities, including ICANS.1 Manage ICANS according to the recommendations in Table 4 and consider further management in accordance with current practice guidelines.1
Grade a | Presenting Symptomsb | Recommendations |
|---|---|---|
Grade 1 | ICE Score 7-9c , OR Depressed level of consciousness (not attributable to any other cause); awakens spontaneously | Withhold elranatamab-bcmm until ICANS resolvesd Monitor neurologic symptoms and consider consultation with neurologist and other specialists for further evaluation and management Consider non-sedating, anti-seizure medications (e.g., levetiracetam) for seizure prophylaxis |
Grade 2 | ICE Score 3-6c , OR Depressed level of consciousness (not attributable to any other cause); awakens to voice | Withhold elranatamab until ICANS resolvesd Administer dexamethasone (or equivalent drug) 10 mg IV every 6 hours; continue dexamethasone use until resolution to grade 1 or less, then taper Monitor neurologic symptoms and consider consultation with neurologist and other specialists for further evaluation and management Consider non-sedating, anti-seizure medications (e.g., levetiracetam) for seizure prophylaxis Monitor daily for 48 hours following the next elranatamab-bcmm dose Instruct patient to remain within proximity of a healthcare facility and consider hospitalization |
Grade 3 (first occurrence) | ICE Score 0-2c , OR Depressed level of consciousness (not attributable to any other cause); awakens only to tactile stimulus, OR Seizures (not attributable to any other cause), either : any clinical seizure, focal or generalized, that resolves rapidly, or non-convulsive seizures on EEG that resolve with intervention, OR Raised intracranial pressure: focal/local edema on neuroimaging (not attributable to any other cause) | Withhold elranatamab until ICANS resolvesd Administer dexamethasone (or equivalent drug) 10 mg IV every 6 hours; continue dexamethasone use until resolution to grade 1 or less, then taper Monitor neurologic symptoms and consider consultation with neurologist and other specialists for further evaluation and management Consider non-sedating, anti-seizure medications (e.g., levetiracetam) for seizure prophylaxis Provide supportive therapy, which may include intensive care Hospitalize patients for 48 hours following the next elranatamab-bcmm dose |
Grade 3 (recurrent) | ICE Score 0-2c , OR Depressed level of consciousness (not attributable to any other cause); awakens only to tactile stimulus, OR Seizures (not attributable to any other cause), either : any clinical seizure, focal or generalized, that resolves rapidly, or non-convulsive seizures on EEG that resolve with intervention, OR Raised intracranial pressure: focal/local edema on neuroimaging (not attributable to any other cause) | Permanently discontinue elranatamab Administer dexamethasone (or equivalent drug) 10 mg IV every 6 hours; continue dexamethasone use until resolution to grade 1 or less, then taper Monitor neurologic symptoms and consider consultation with neurologist and other specialists for further evaluation and management Consider non-sedating, anti-seizure medications (e.g., levetiracetam) for seizure prophylaxis Provide supportive therapy, which may include intensive care |
Grade 4 | ICE Score 0c , OR Depressed level of consciousness (not attributable to any other cause), either: unarousable or requires vigorous or repetitive tactile stimuli to arouse, or stupor or coma, OR Seizures (not attributable to any other cause), either : life-threatening prolonged seizure (>5 minutes), or repetitive clinical or electrical seizures without return to baseline in between, OR Motor findings (not attributable to any other cause): deep focal motor weakness such as hemiparesis or paraparesis, OR Raised intracranial pressure/cerebral edema (not attributable to any other cause), with signs/symptoms such as diffuse cerebral edema on neuroimaging, or decerebrate or decorticate posturing, or cranial nerve VI palsy, or papilledema, or Cushing's triad. | Permanently discontinue elranatamab Administer dexamethasone (or equivalent drug) 10 mg IV every 6 hours; continue dexamethasone use until resolution to grade 1 or less, then taper. Alternatively, consider administration of methylprednisolone 1000 mg per day IV for 3 days Monitor neurologic symptoms and consider consultation with neurologist and other specialists for further evaluation and management Consider non-sedating, anti-seizure medications (e.g., levetiracetam) for seizure prophylaxis Provide supportive therapy, which may include intensive care |
aBased on American Society for Transplantation and Cellular Therapy (ASTCT) 2019 grading criteria for ICANS.
bManagement is based on most severe event, not attributable to other cause.
cIf 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 3 objects, e.g., point to clock, pen, button = 3 points); Following Commands (e.g., “show me 2 fingers” or “close your eyes and stick out your tongue” = 1 point); Writing (ability to write a standard sentence = 1 point); and Attention (count backwards from 100 by 10 = 1 point). If patient is unarousable and unable to perform ICE Assessment (Grade 4 ICANS) = 0 points.
dRefer to Table 2 for recommendations on restarting elranatamab after a dose delay.
Severity of Neurologic Toxicity (Excluding ICANS) | Recommendations |
|---|---|
Grade 1 | Withhold elranatamab until neurologic toxicity symptoms resolve or stabilize |
Grade 2 or grade 3 (first occurrence) | Withhold elranatamab until neurologic symptoms improve to grade 1 or less Provide supportive therapy |
Grade 3 (recurrent) or grade 4 | Permanently discontinue elranatamab Provide supportive therapy, which may include intensive care |
Refer to Table 6 for the management of other toxicities, including hematologic adverse reactions, infections, and other non-hematologic adverse reactions.1
Adverse Reaction | Severity | Recommendations |
|---|---|---|
Hematologic adverse reactions | Absolute neutrophil count <0.5 x 109/L | Withhold elranatamab until absolute neutrophil count is ≥0.5 x 109/Lb |
Hematologic adverse reactions | Febrile neutropenia | Withhold elranatamab until absolute neutrophil count is ≥1 x 109/L and fever resolvesb |
Hematologic adverse reactions | Hemoglobin <8 g/dL | Withhold elranatamab until hemoglobin is ≥8 g/dL b |
Hematologic adverse reactions | Platelet count <25,000/mcL, or between 25,000/mcL and 50,000/mcL with bleeding | Withhold elranatamab until platelet count is ≥25,000/mcL and no evidence of bleedingb |
Infections and other non-hematologic adverse reactionsa | Grade 3 | Withhold elranatamab until adverse reaction improves to grade 1 or less, or baseline b |
Infections and other non-hematologic adverse reactionsa | Grade 4 | Consider permanent discontinuation of elranatamab If not permanently discontinued, withhold subsequent treatment doses (doses administered after step-up dosing schedule) until adverse reaction improves to grade 1 or less |
aBased on National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE), Version 5.0.
bRefer to Table 2 for recommendations on restarting elranatamab-bcmm after a dose delay.
The manufacturer makes no specific dosage recommendations for patients with hepatic impairment.1
The manufacturer makes no specific dosage recommendations for patients with renal impairment.1
The manufacturer makes no specific dosage recommendations for geriatric patients.1
Cytokine Release Syndrome (CRS)
A boxed warning about the risk of CRS is included in the prescribing information for elranatamab-bcmm.1 CRS, including life-threatening or fatal reactions, can occur.1
In the elranatamab-bcmm clinical trial, CRS occurred in 58% of patients who received elranatamab at the recommended dosing schedule, with grade 1, grade 2, and grade 3 CRS occurring in 44, 14, and 0.5% of patients, respectively.1 Recurrent CRS occurred in 13% of patients.1 Most patients experienced CRS after the first (43%) or second (19%) step-up dose; 7% had CRS after the first treatment dose and 1.6% after a subsequent dose.1 The median time to onset of CRS was 2 days (range, 1-9) after the most recent dose, with a median duration of 2 days (range, 1-19).1
Clinical signs and symptoms of CRS may include, but are not limited to, fever, hypoxia, chills, hypotension, tachycardia, headache, and elevated liver enzymes.1
To reduce the risk of CRS, initiate elranatamab using the step-up dosing schedule.1 Monitor patients following administration of elranatamab.1 Administer pretreatment medications prior to each dose in the step-up dosing schedule (see Administration and Preparation).1
Inform patients to seek medical attention if they experience signs or symptoms of CRS.1 At the first sign of CRS, immediately evaluate patients for hospitalization.1 Manage CRS according to the recommendations (see "Dosage Modification for Toxicity" under Dosage) and consider further management in accordance with current practice guidelines.1 Withhold or permanently discontinue elranatamab based on reaction severity.1
Because of the risk of CRS, elranatamab-bcmm is available only through a Risk Evaluation and Mitigation Strategy (REMS) program (See "REMS" under Dosage and Administration).1 For further information, consult the Elrexfio®REMS program website ([Web]) or call 1-844-923-7845.1, 2
Neurologic Toxicity, including Immune Effector Cell-Associated Neurotoxicity Syndrome (ICANS)
A boxed warning about the risk of neurologic toxicity is included in the prescribing information for elranatamab-bcmm.1 Serious and life-threatening neurologic toxicity, including ICANS, can occur in patients receiving elranatamab.1
In the elranatamab-bcmm clinical trial, neurologic toxicity occurred in 59% of patients who received elranatamab-bcmm at the recommended dosing schedule, with grade 3 or 4 neurologic toxicity occurring in 7% of patients.1 Reported neurologic toxicities included headache, encephalopathy, motor dysfunction, sensory neuropathy, and Guillain-Barré syndrome.1
In the clinical trial, ICANS occurred in 3.3% of patients who received elranatamab at the recommended dosing schedule.1 Most patients experienced ICANS after the first step-up dose (2.7%), 1 (0.5%) patient experienced ICANS after the second step-up dose, and 1 (0.5%) patient experienced ICANS after subsequent dose(s).1 Recurrent ICANS occurred in 1.1% of patients.1 The median time to onset was 3 days (range, 1-4) after the most recent dose, with a median duration of 2 days (range, 1-18).1 The most frequent clinical manifestations of ICANS included depressed level of consciousness and grade 1 or grade 2 Immune Effector Cell-Associated Encephalopathy (ICE) scores.1 The onset of ICANS can be concurrent with CRS, following resolution of CRS, or in the absence of CRS.1
Inform patients to seek medical attention if they experience signs or symptoms of neurologic toxicity.1 Monitor for signs and symptoms of neurologic toxicity during treatment with elranatamab.1 At the first sign of neurologic toxicity, including ICANS, evaluate and treat patients immediately based on reaction severity.1 Withhold or permanently discontinue elranatamab-bcmm based on severity and consider further management in accordance with current practice guidelines.1
Due to the potential for neurologic toxicity including ICANS, patients receiving elranatamab are at risk of depressed level of consciousness.1 Advise patients not to drive or operate heavy or potentially dangerous machinery for 48 hours after completing each of the 2 step-up doses and the first treatment dose within the elranatamab-bcmm step-up dosing schedule, and in the event of new onset of any neurological toxicity symptoms until symptoms resolve.1
Because of the risk of CRS, elranatamab-bcmm is available only through a REMS program (See "REMS" under Dosage and Administration).1 For further information, consult the Elrexfio®REMS program website ([Web]) or call 1-844-923-7845.1, 2
Other Warnings and Precautions
Elranatamab can cause severe, life-threatening, or fatal infections.1
In the elranatamab-bcmm clinical trial, serious infections, including opportunistic infections, occurred in 42% of patients who received elranatamab at the recommended dosing schedule, with grade 3 or 4 infections in 31% of patients, and fatal infections in 7% of patients.1 The most common serious infections reported were pneumonia and sepsis.1
Do not initiate treatment in patients with active infections.1 Monitor patients for signs and symptoms of infection prior to and during treatment with elranatamab; treat infections as appropriate.1 Withhold or permanently discontinue elranatamab based on infection severity.1 Administer prophylactic antimicrobial and anti-viral medications in accordance with current practice guidelines.1 Consider treatment with subcutaneous or IV immunoglobulin as appropriate.1
Elranatamab can cause neutropenia and febrile neutropenia.1
In the elranatamab-bcmm clinical trial, decreased neutrophils occurred in 62% of patients, with grade 3 or 4 decreased neutrophils in 51% of patients.1 Febrile neutropenia occurred in 2.2% of patients.1
Monitor CBC at baseline and periodically during treatment.1 Provide supportive care in accordance with current practice guidelines.1 Monitor patients with neutropenia for signs of infection and withhold elranatamab based on severity.1
Elranatamab can cause hepatotoxicity.1
In the elranatamab-bcmm clinical trial, elevated ALT occurred in 36% of patients, with grade 3 or 4 ALT elevation occurring in 3.8% of patients.1 Elevated AST occurred in 40% of patients, with grade 3 or 4 AST elevation occurring in 6% of patients.1 Grade 3 or 4 total bilirubin elevations occurred in 0.5% of patients.1 Liver enzyme elevation can occur with or without concurrent CRS.1
Monitor liver enzymes and bilirubin at baseline and during treatment as clinically indicated.1 Withhold elranatamab or consider permanent discontinuation based on severity (see "Dosage Modification for Toxicity" under Dosage).1
Based on the mechanism of action, elranatamab may cause fetal harm when administered to pregnant women.1 There are no available data on use of elranatamab-bcmm in pregnant women; no animal reproductive or developmental toxicity studies have been performed with the drug to date.1 Elranatamab causes immune activation, which may compromise pregnancy maintenance.1 Based on studies in non-pregnant animals, elranatamab can cause B-cell lymphocytopenia in infants exposed to the drug in-utero.1 Human immunoglobulin G (IgG) crosses the placenta; therefore, there is potential for maternal transmission of elranatamab to the developing fetus.1
Apprise pregnant women and females of reproductive potential of the potential risk to the fetus.1 Verify the pregnancy status of females of reproductive potential prior to initiating treatment with elranatamab-bcmm.1 Advise females of reproductive potential to use effective contraception during treatment with elranatamab and for 4 months after the last dose.1
There is potential for immunogenicity with elranatamab.1
In the elranatamab-bcmm clinical trial, of 168 patients who received the drug for up to 24 months and were evaluable for presence of anti-drug antibodies (ADAs) against elranatamab, 15 (8.9%) tested positive for ADAs.1 Among these 15 patients, 9 (60%) tested positive for neutralizing antibodies against elranatamab.1
The effect of these antibodies on the pharmacokinetics, pharmacodynamics, safety, and/or effectiveness of elranatamab is unknown.1
Based on the mechanism of action of elranatamab, fetal harm may occur when the drug is administered during pregnancy.1 No data are available on the use of elranatamab in pregnant women to evaluate for a drug-associated risk.1 No animal reproductive or developmental toxicity studies have been performed to date.1
Elranatamab causes T-cell activation and cytokine release; immune activation may compromise the maintenance of pregnancy.1 Based on the finding of B-cell depletion in non-pregnant animals, elranatamab can cause B-cell lymphocytopenia in infants exposed to the drug in-utero.1 Because human IgG is known to cross the placenta after the first trimester of pregnancy, there is potential for maternal transmission of elranatamab to the developing fetus.1
Apprise pregnant women and females of reproductive potential of the potential risk to the fetus.1 Verify pregnancy status in females of reproductive potential prior to initiating treatment with elranatamab-bcmm.1 Elranatamab is associated with hypogammaglobulinemia; therefore, consider assessment of immunoglobulin levels in newborns of mothers treated with elranatamab.
It is unknown whether elranatamab distributes into human milk, or affects the breast-fed child or the production of milk.1 Maternal IgG is known to be present in human milk.1
Because of the potential for serious adverse effects in the breast-fed child, advise women not to breast-feed during treatment and for 4 months after the last dose.1
Females and Males of Reproductive Potential
Verify pregnancy status in females of reproductive potential prior to initiating treatment with elranatamab.1 Advise females of reproductive potential to use effective contraception during treatment and for 4 months after the last dose.1
Safety and efficacy of elranatamab have not been established in pediatric patients.1
In the elranatamab-bcmm clinical trial, 62% of patients treated with the drug were ≥65 years of age, and 19% were ≥75 years of age.1 No overall differences in safety or efficacy were observed in patients 65-74 years of age compared to younger adults.1 Clinical studies did not include sufficient numbers of patients ≥75 years of age to determine whether they respond differently than younger patients.1
There were no clinically important differences in elranatamab pharmacokinetics based on mild hepatic impairment (total bilirubin 1 to ≤1.5 times upper limit of normal [ULN], or any AST greater than ULN).1 The effects of moderate to severe hepatic impairment (total bilirubin >1.5 times ULN and any AST) on elranatamab-bcmm pharmacokinetics are unknown.1
There were no clinically important differences in elranatamab pharmacokinetics based on mild or moderate renal impairment (estimated glomerular filtration rate [eGFR] 30-89 mL/minute).1 The effect of severe renal impairment (eGFR 15-29 mL/minute) or end-stage renal disease (eGFR <15 mL/minute) on elranatamab pharmacokinetics is unknown.1
The most common adverse effects (incidence ≥20%) of elranatamab in clinical trials were CRS, fatigue, injection site reaction, diarrhea, upper respiratory tract infection, musculoskeletal pain, pneumonia, decreased appetite, rash, cough, nausea, and pyrexia.1
No formal studies assessing the drug interaction potential of elranatamab have been performed to date.1
Drugs Affecting or Affected by Hepatic Microsomal Enzymes
Elranatamab causes the release of cytokines that may suppress the activity of cytochrome P-450 (CYP) enzymes, which can result in increased exposure of CYP substrates.1 Increased exposure of CYP substrates is more likely to occur after the first dose of elranatamab (day 1) and ≤14 days after the 32 mg dose (day 4), and also during and following episodes of CRS.1
For certain CYP substrates, minimal changes in substrate plasma concentration may lead to serious adverse events.1 Monitor for toxicity or plasma concentrations of such CYP substrates when they are given concomitantly with elranatamab-bcmm.1
Elranatamab is a bispecific B-cell maturation antigen (BCMA)-directed T-cell engaging antibody that binds to BCMA on plasma cells, plasmablasts, and multiple myeloma cells, and to CD3 on T-cells; this leads to cytolysis of the BCMA-expressing cells.1 Elranatamab-activated T-cells cause proinflammatory cytokine release, resulting in multiple myeloma cell lysis.1
Transient elevation of circulating cytokines interleukin (IL)-2, IL-6, IL-8, IL-10, tumor necrosis factor-α, and interferon-γ is observed at dosage levels of 30 mcg/kg (0.03 times the approved recommended dosage) and higher.1 After administration of elranatamab, the highest elevation of cytokines is generally observed within 72 hours after the first dose (12 mg) on day 1; levels generally return to baseline prior to the administration of the first full dose (76 mg) on day 8.1
Elranatamab exhibits dose proportional pharmacokinetics over the dose range 6-76 mg (0.079-1 times the approved recommended dose).1 The peak plasma concentration of elranatamab-bcmm is achieved at the end of the weekly dosing regimen (i.e., at week 24 of 76 mg weekly dosing).1 The mean bioavailability of elranatamab-bcmm is 56.2% when administered subcutaneously.1 The median time to peak plasma drug concentration is 7 days (range, 3-7) following subcutaneous administration.1 Elranatamab is expected to undergo metabolism via catabolic pathways into small peptides.1 The half-life is 22 days at the 76 mg dosage.1 No clinically important differences in the pharmacokinetics of elranatamab-bcmm were observed based on age (36-89 years), sex, race (white, Asian, or Black), or body weight (37-160 kg).1
Additional Information
The American Society of Health-System Pharmacists, Inc. represents that the information provided in the accompanying monograph was formulated with a reasonable standard of care, and in conformity with professional standards in the field. Readers are advised that decisions regarding use of drugs are complex medical decisions requiring the independent, informed decision of an appropriate health care professional, and that the information contained in the monograph is provided for informational purposes only. The manufacturer's labeling should be consulted for more detailed information. The American Society of Health-System Pharmacists, Inc. does not endorse or recommend the use of any drug. The information contained in the monograph is not a substitute for medical care. For further information on the handling of antineoplastic agents, see the ASHP Guidelines on Handling Hazardous Drugs at [Web].
Excipients in commercially available drug preparations may have clinically important effects in some individuals; consult specific product labeling for details.
Please refer to the ASHP Drug Shortages Resource Center for information on shortages of one or more of these preparations.
Distribution of elranatamab-bcmm is restricted.1, 2 (See REMS under Dosage and Administration.)
Routes | Dosage Forms | Strengths | Brand Names | Manufacturer |
|---|---|---|---|---|
Parenteral | Injection, for subcutaneous use | 44 mg/1.1 mL (40 mg/mL) | Elrexfio® | Pfizer |
76 mg/1.9 mL (40 mg/mL) | Elrexfio® | Pfizer |
AHFS® Drug Information. © Copyright, 1959-2026, Selected Revisions June 10, 2026. American Society of Health-System Pharmacists, Inc., 4500 East-West Highway, Suite 900, Bethesda, MD 20814.
Only references cited for selected revisions after 1984 are available electronically.
1. Pfizer Laboratories Div Pfizer Inc. ELREXFIO®(elranatamab-bcmm) SUBCUTANEOUS prescribing information. 2026 Feb. [Web]
2. US Food and Drug Administration. Search orphan drug designations and approvals. From FDA website. [Web]
3. Lesokhin A, Tomasson M, Arnulf B, et al. Elranatamab in relapsed or refractory multiple myeloma: phase 2 MagnetisMM-3 trial results. Nat Med. 2023;29:2259-2267.
4. Hicks LK, Messersmith HJ, Hadidi SA, et al. Treatment of multiple myeloma: ASCO-Ontario Health (Cancer Care Ontario) living guideline. J Clin Oncol . 2026;1-28.
5. Pfizer Inc. ELREXFIO® Risk Evaluation and Mitigation Strategy (REMS). [Web]