Elranatamab-bcmm (Monograph)

Drug class: Antineoplastic Agents

Medically reviewed by Drugs.com on Aug 10, 2024. Written by ASHP.

[Web]

Introduction

Antineoplastic agent; a bispecific B-cell maturation antigen (BCMA)-directed CD3 T-cell engager.¹

Uses for Elranatamab-bcmm

Multiple Myeloma

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 3} (designated an orphan drug by FDA for this use).²

Current indication approved under accelerated approval based on response rate and durability of response; continued approval may be contingent upon verification of clinical benefit in a confirmatory trial.¹

The American Society of Clinical Oncology (ASCO) and Cancer Care Ontario (CCO) guidelines recommend triplet therapy, defined as a regimen with 2 novel agents (immunomodulatory drug, proteasome inhibitor, or monoclonal antibody) plus a corticosteroid for treatment of relapsed or refractory disease.⁴ The guidelines were published prior to availability of elranatamab.⁴

Elranatamab-bcmm Dosage and Administration

General

Pretreatment Screening

• Monitor for signs and symptoms of infection prior to initiating therapy.¹

• Monitor CBC prior to initiating therapy.¹

• Monitor liver enzymes and bilirubin prior to initiating therapy.¹

• Verify pregnancy status in females of reproductive potential prior to initiating therapy.¹

Patient Monitoring

• Monitor for signs and symptoms of CRS following administration.¹

• Monitor for signs and symptoms of neurologic toxicity, including ICANS, during treatment.¹

• Monitor for signs and symptoms of infection during treatment; evaluate and treat promptly.¹

• Monitor CBC periodically during treatment; monitor patients with neutropenia for signs of infection.¹

• Monitor liver enzymes and bilirubin during treatment as clinically indicated.¹

Premedication and Prophylaxis

• Administer the following pretreatment medications approximately 1 hour before each dose in the elranatamab-bcmm step-up dosing schedule (i.e., step-up dose 1, step-up dose 2, and 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

Dispensing and Administration Precautions

• Elranatamab-bcmm should only be administered by a qualified healthcare professional with appropriate medical support to manage severe reactions such as CRS and neurologic toxicity, including ICANS.¹

• Administer elranatamab-bcmm according to the step-up dosing schedule to reduce the incidence and severity of CRS.¹

• Hospitalize patients for 48 hours after administration of the first step-up dose, and for 24 hours after the second step-up dose, due to the risk of CRS.¹

REMS

• Because of the risks of CRS and neurologic toxicity, including ICANS, elranatamab-bcmm is available only through a restricted distribution program called the Elrexfio REMS.¹ For further information, consult the Elrexfio REMS program website ([Web]) or call 1-844-923-7845.^{1 2}

• Prescribers must be certified with the REMS program by enrolling and completing training.¹

• Prescribers must counsel patients on the risks of CRS and neurologic toxicity, including ICANS, and provide patients with a Patient Wallet Card.¹

• Pharmacies and healthcare settings that dispense elranatamab-bcmm must be certified with the program and must verify prescriber certification prior to dispensing elranatamab-bcmm.¹

• Wholesalers and distributors must only distribute elranatamab-bcmm to certified pharmacies or healthcare settings.¹

Administration

Sub-Q Administration

Administer by sub-Q injection by a healthcare professional.¹ Should only be administered by qualified healthcare professionals with sufficient and appropriate medical support to manage severe reactions such as CRS and neurologic toxicity (including ICANS).¹

Available as solution supplied in single-dose vial containing 76 mg/1.9 mL (40 mg/mL) or 44 mg/1.1 mL (40 mg/mL).¹ Vials are preservative-free; for one-time use only in a single patient.¹

Administer according to step-up dosing schedule to reduce incidence and severity of CRS.¹ Administer the following pretreatment medications approximately 1 hour before the first 3 doses in step-up dosing schedule (i.e., step-up dose 1, step-up dose 2, and first treatment dose): acetaminophen (or equivalent) 650 mg orally, dexamethasone (or equivalent) 20 mg orally or IV, and diphenhydramine (or equivalent) 25 mg orally.¹ Hospitalize patients for 48 hours after administration of first step-up dose, and for 24 hours after second step-up dose.¹

Use aseptic technique for preparation and administration.¹ Supplied as a ready-to-use solution; dilution notrequired prior to administration.¹ Depending on required dose, use a 44 mg/1.1 mL (40 mg/mL) single-dose vial for step-up doses 1 or 2, and a 76 mg/1.9 mL (40 mg/mL) single-dose vial for treatment doses.¹ 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

To prepare, remove appropriate strength vial from refrigerator and allow to equilibrate to ambient temperature (15–30°C); do not warm vial in any other manner.¹ Once equilibrated, withdraw required injection volume from vial into an appropriately sized syringe with stainless steel injection needles (30G or wider) and polypropylene or polycarbonate syringe material; discard unused portions of the drug.¹

Do not administer if particulate matter or discoloration observed.¹ Preferred sub-Q injection site is abdomen; may also be injected into other sites (e.g., thigh).¹ Do not inject into tattoos, scars, or areas where skin may be red, bruised, tender, hard, or not intact.¹

Dosage

Adults

Relapsed or Refractory Multiple Myeloma

Sub-Q

See Table 1 for recommended dosing schedule.¹

For patients who received ≥24 weeks of treatment, achieved a response (partial response or better), and maintained this response for ≥2 months, transition dose interval to an every-2-week schedule.¹

Continue treatment until disease progression or unacceptable toxicity.¹

Administer pretreatment medications prior to each dose in step-up dosing schedule (i.e., step-up dose 1, step-up dose 2, and first treatment dose).¹

Dosage Interruption for Toxicity

Dosage delays may be required to manage toxicities.¹

If dose delayed, restart therapy based on recommendations in Table 2; resume dosing schedule accordingly.¹ Administer pre-medications as indicated in Table 2.¹

Consider the risks and benefits of restarting elranatamab in patients who require a dosage delay of >42 days due to an adverse reaction.

Dosage Modification for Toxicity

Dose reductions not recommended; dosage delays may be required to manage toxicities.¹

Refer to Table 2 for recommendations on restarting after a dose delay.¹

If CRS suspected, withhold elranatamab until CRS resolves.¹ Manage CRS according to recommendations in Table 3; consider further management in accordance with current practice guidelines.¹ Administer supportive therapy for CRS (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

Based on American Society for Transplantation and Cellular Therapy (ASTCT) 2019 grading criteria for CRS.

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.

Low-flow nasal cannula is ≤6 L/min; high-flow nasal cannula is >6 L/min.

Refer 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 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 (may include intensive care) for severe or life-threatening neurologic toxicities, including ICANS.¹ Manage ICANS according to the recommendations in Table 4; consider further management in accordance with current practice guidelines.¹

Based on American Society for Transplantation and Cellular Therapy (ASTCT) 2019 grading criteria for ICANS.

Management is based on most severe event, not attributable to other cause.

If 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.

Refer to Table 2 for recommendations on restarting elranatamab-bcmm after a dose delay.

Refer to Table 6 for management of other toxicities, including hematologic adverse reactions, infections, and other non-hematologic adverse reactions.¹

Based on National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE), Version 5.0.

Refer to Table 2 for recommendations on restarting elranatamab after a dose delay.

Special Populations

Hepatic Impairment

No specific dosage recommendations at this time.¹

Renal Impairment

No specific dosage recommendations at this time.¹

Geriatric Patients

No specific dosage recommendations at this time.¹

Related/similar drugs

Carvykti, Tecvayli, Revlimid, Darzalex, Velcade, Pomalyst, Kyprolis

Cautions for Elranatamab-bcmm

Contraindications

• None.¹

Warnings/Precautions

Warnings

Cytokine Release Syndrome (CRS)

CRS, including life-threatening or fatal reactions, can occur (see Boxed Warning).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 risk of CRS, initiate elranatamab using step-up dosing schedule.¹ Monitor patients following administration.¹ Administer pretreatment medications prior to each dose in step-up dosing schedule.¹

Inform patients to seek medical attention if they experience signs or symptoms of CRS.¹ At first sign of CRS, immediately evaluate patients for hospitalization.¹ Manage CRS according to recommendations; consider further management in accordance with current practice guidelines.¹ Withhold or permanently discontinue elranatamab-bcmm based on severity.¹

Because of risk of CRS, elranatamab-bcmm available only through a REMS program.¹ For further information, consult ElrexfioREMS program website ([Web]) or call 1-844-923-7845.^{1 2}

Neurologic Toxicity, including ICANS

Serious and life-threatening neurologic toxicity, including ICANS, can occur (see Boxed Warning).¹

Reported neurologic toxicities included headache, encephalopathy, motor dysfunction, sensory neuropathy, and Guillain-Barré syndrome.¹ Onset of ICANS can be concurrent with CRS, following resolution of CRS, or in 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.¹ At first sign of neurologic toxicity, including ICANS, evaluate and treat patients immediately based on severity.¹ Withhold or permanently discontinue elranatamab-bcmm based on severity; consider further management in accordance with current practice guidelines.¹

Patients 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 first treatment dose within the step-up dosing schedule, and in the event of new onset of any neurological toxicity symptoms until symptoms resolve.¹

Because of risk of CRS, elranatamab-bcmm available only through a REMS program.¹ For further information, consult Elrexfio REMS program website ([Web]) or call 1-844-923-7845.^{1 2}

<C> Other Warnings and Precautions

Infections

Severe, life-threatening, or fatal infections reported, including opportunistic infections.¹ Most common serious infections were pneumonia and sepsis.¹

Do not initiate treatment in patients with active infections.¹ Monitor for signs and symptoms of infection prior to and during treatment; treat infections appropriately.¹ Withhold or permanently discontinue elranatamab-bcmm based on severity.¹ Administer prophylactic antimicrobial and anti-viral medications according to current practice guidelines.¹ Consider sub-Q or IV immunoglobulin as appropriate.¹

Neutropenia

Neutropenia and febrile neutropenia reported.¹

Monitor CBC at baseline and periodically during treatment.¹ Provide supportive care according to current practice guidelines.¹ Monitor patients with neutropenia for signs of infection and withhold elranatamab based on severity.¹

Hepatotoxicity

Hepatotoxicity may occur.¹ Elevated ALT, AST, and total bilirubin reported, including grade 3 or 4 elevations.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

Fetal/Neonatal Morbidity and Mortality

May cause fetal harm based on mechanism of action.¹ No data available on use in pregnant women; no animal reproductive or developmental toxicity studies performed.

Causes immune activation, which may compromise pregnancy maintenance.¹ Based on studies in non-pregnant animals, can cause B-cell lymphocytopenia in infants exposed to elranatamab in-utero.¹ Human IgG crosses placenta; potential for maternal transmission to developing fetus.¹

Apprise pregnant women and females of reproductive potential of potential risk to fetus.¹ Verify pregnancy status in females of reproductive potential prior to initiating treatment.¹ Advise females of reproductive potential to use effective contraception during treatment and for 4 months after the last dose.¹

Immunogenicity

Potential for immunogenicity.¹ Development of anti–elranatamab (including neutralizing) antibodies reported.¹ Effect on pharmacokinetics, pharmacodynamics, safety, and/or effectiveness of elranatamab unknown.¹

Specific Populations

Pregnancy

May cause fetal harm based on mechanism of action.¹ No data available on use in pregnant women.¹ No animal reproductive or developmental toxicity studies performed to date.¹

Causes T-cell activation and cytokine release; immune activation may compromise pregnancy maintenance.¹ Based on finding of B-cell depletion in non-pregnant animals, can cause B-cell lymphocytopenia in infants exposed in-utero.¹

Human IgG crosses placenta after first trimester of pregnancy; potential for elranatamab to be transmitted from mother to developing fetus.¹

Apprise pregnant women and females of reproductive potential of potential risk to fetus.¹ Verify pregnancy status in females of reproductive potential prior to initiating treatment.¹

Elranatamab associated with hypogammaglobulinemia; consider assessment of immunoglobulin levels in newborns of mothers treated with elranatamab.¹

Lactation

Unknown whether elranatamab distributes into human milk, or affects breast-fed child or production of milk.¹ Maternal IgG known to be present in human milk.¹

Because of potential for serious adverse effects in breast-fed child, advise women not to breast-feed during treatment with elranatamab 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.¹ Advise females of reproductive potential to use effective contraception during treatment with elranatamab and for 4 months after the last dose.¹

Pediatric Use

Safety and efficacy not established.¹

Geriatric Use

No overall differences in safety or efficacy observed in patients 65–74 years of age compared to younger adults.¹ Insufficient experience in patients ≥75 years of age to determine whether they respond differently than younger patients.¹

Hepatic Impairment

No clinically important differences in pharmacokinetics based on mild hepatic impairment (total bilirubin 1 to ≤1.5 times ULN, or any AST greater than ULN).¹ Effect of moderate to severe hepatic impairment (total bilirubin >1.5 times ULN and any AST) on pharmacokinetics unknown.¹

Renal Impairment

No clinically important differences in pharmacokinetics based on mild or moderate renal impairment (eGFR 30–89 mL/minute).¹ Effect of severe renal impairment (eGFR 15–29 mL/minute) or end-stage renal disease (eGFR <15 mL/minute) on pharmacokinetics unknown.¹

Common Adverse Effects

Common adverse effects (≥20%): CRS, fatigue, injection site reaction, diarrhea, upper respiratory tract infection, musculoskeletal pain, pneumonia, decreased appetite, rash, cough, nausea, pyrexia.¹

Drug Interactions

No formal drug interaction studies performed to date.¹

Drugs Affecting or Affected by Hepatic Microsomal Enzymes

Causes release of cytokines that may suppress activity of CYP enzymes, resulting in increased exposure of CYP substrates.¹ Increased CYP substrate exposure more likely to occur after first dose of elranatamab-bcmm (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 given concomitantly with elranatamab.¹

Elranatamab-bcmm Pharmacokinetics

Absorption

Bioavailability

Mean bioavailability 56.2% when administered sub-Q.¹

Dose proportional pharmacokinetics over dosage range 6–76 mg.¹

Peak plasma concentration achieved at end of weekly dosing regimen (i.e., at week 24 of 76 mg weekly dosing).¹

Median time to peak plasma concentration following sub-Q administration: 7 days (range, 3–7).¹

Distribution

Extent

Not known if elranatamab crosses placenta or distributes into human milk; however, human IgG crosses placenta and distributes into milk.¹

Elimination

Metabolism

Expected to undergo metabolism via catabolic pathways into small peptides.¹

Half-life

22 days at 76 mg dosage.¹

Special Populations

No clinically important differences in pharmacokinetics observed based on age (36–89 years), sex, race (white, Asian, or Black), and body weight (37–160 kg).¹

Stability

Storage

Parenteral

Injection, for Sub-Q Use

Unopened vials: store refrigerated at 2–8°C in original carton to protect from light; do not freeze or shake.¹

Prepared syringe: If not used immediately, store at 2–8°C for a maximum of 4 hours.¹

Actions

• Bispecific B-cell maturation antigen (BCMA)-directed T-cell engaging antibody.¹

• Binds BCMA on plasma cells, plasmablasts, and multiple myeloma cells, and CD3 on T-cells; leads to cytolysis of BCMA-expressing cells.¹

• Activates T-cells to cause release of proinflammatory cytokines, resulting in multiple myeloma cell lysis.¹

Advice to Patients

• Advise patients to read the FDA-approved patient labeling (Medication Guide).¹

• Advise patients to contact their clinician immediately if they experience any signs or symptoms of cytokine release syndrome (CRS), which include but are not limited to fever, hypoxia, chills, hypotension, tachycardia, and elevated liver enzymes.¹

• Inform patients that they will be hospitalized for 48 hours after administration of the first step-up dose of elranatamab-bcmm, and for 24 hours after administration of the second step-up dose.¹

• Advise patients to contact their clinician immediately if they experience any signs or symptoms of neurologic toxicity, including immune effector cell-associated neurotoxicity syndrome (ICANS).¹ Inform patients of the signs and symptoms of neurologic toxicity (including ICANS), which include headache, encephalopathy, motor dysfunction, sensory neuropathy, and Guillain-Barré syndrome.¹

• Advise patients to refrain from driving or operating 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, or in the case of new onset of neurological toxicity symptoms, until symptoms resolve.¹

• Inform patients that elranatamab-bcmm is available only through a restricted program called the Elrexfio REMS.¹ Inform patients that they will receive a Patient Wallet Card that must be carried with them at all times and shown to all of their clinicians.¹ Inform patients that the card describes signs and symptoms of CRS and neurologic toxicity (including ICANS) which, if they develop, should prompt them to immediately seek medical care.¹

• Inform patients of the signs and symptoms of infection.¹

• Inform patients of the signs and symptoms associated with neutropenia and febrile neutropenia.¹

• Advise patients that liver enzyme elevations may occur during treatment with elranatamab-bcmm.¹ Advise patients to report symptoms that may indicate liver toxicity, including fatigue, anorexia, right upper abdominal discomfort, dark urine, or jaundice.¹

• Advise women to inform their clinician if they are or plan to become pregnant.¹ Apprise pregnant women and females of reproductive potential of the potential hazard to a fetus.¹ Advise females of reproductive potential to use effective contraception during treatment with elranatamab-bcmm and for 4 months after the last dose.¹

• Advise women to inform their clinician if they are or plan to breast-feed.¹ Advise women not to breast-feed during treatment with elranatamab-bcmm and for 4 months after the last dose.¹

• Advise patients to inform their clinician of existing or contemplated concomitant therapy, including prescription and OTC drugs and dietary or herbal supplements, as well as any concomitant illnesses.¹

• Inform patients of other important precautionary information.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].

Preparations

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.

Distrubution of elranatamab-bcmm is restricted.^{1 2} (See "REMS" under Dosage and Administration)

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