Introduction

Elranatamab-bcmm, a bispecific B-cell maturation antigen (BCMA)-directed CD3 T-cell engager, is an antineoplastic agent.

Uses for Elranatamab (Systemic)

Elranatamab-bcmm has the following uses:

Elranatamab-bcmm 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 a 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 a confirmatory trial(s).

Elranatamab (Systemic) Dosage and Administration

General

Elranatamab-bcmm is available in the following dosage form(s) and strength(s):

Injection:

• 76 mg/1.9 mL (40 mg/mL) in a single-dose vial for subcutaneous injection.

• 44 mg/1.1 mL (40 mg/mL) in a single-dose vial for subcutaneous injection.

Dosage

It is essential that the manufacturer's labeling be consulted for more detailed information on dosage and administration of this drug. Dosage summary:

Adults

Dosage and Administration

The recommended dosing schedule for elranatamab-bcmm is provided in the following table. Initiate treatment with a step-up dosing schedule to reduce risk of cytokine release syndrome (CRS). For patients who have received at least 24 weeks of treatment with elranatamab-bcmm and have achieved a response (partial response [PR] or better) and maintained this response for at least 2 months, the dosing interval should transition to an every 2-week schedule.

• 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.

• See Full Prescribing Information for instructions on preparation and administration.

• For subcutaneous injection only.

• Administer pre-treatment medications as recommended.

• Dosage delays may be required to manage toxicities. See Full Prescribing Information for specific instructions.

• If a dose of elranatamab-bcmm is delayed, restart therapy as recommended. See Full Prescribing Information for specific instructions.

Contraindications

None.

Warnings/Precautions

Cytokine Release Syndrome (CRS)

Elranatamab-bcmm can cause CRS, including life-threatening or fatal reactions.

In the clinical trial, CRS occurred in 58% of patients who received elranatamab-bcmm at the recommended dosing schedule, with Grade 1 CRS in 44% of patients, Grade 2 CRS in 14% of patients, and Grade 3 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 a subsequent dose. The median time to onset of CRS was 2 (range: 1 to 9) days after the most recent dose, with a median duration of 2 (range: 1 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 elranatamab-bcmm step-up dosing schedule to reduce risk of CRS and monitor patients following administration of elranatamab-bcmm accordingly. Administer pre-treatment medications prior to each dose in the step-up dosing schedule to reduce risk of CRS.

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 elranatamab-bcmm based on severity.

Elranatamab-bcmm is available only through a restricted program under a REMS.

Neurologic Toxicity, Including Immune Effector Cell-associated Neurotoxicity Syndrome (ICANS)

Elranatamab-bcmm can cause serious or life-threatening neurologic toxicity, including ICANS.

In the 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. Neurologic toxicities included headache (18%), encephalopathy (15%), motor dysfunction (13%), sensory neuropathy (13%), and Guillain-Barré Syndrome (0.5%).

In the clinical trial, ICANS occurred in 3.3% of patients who received elranatamab-bcmm at the recommended dosing schedule. Most patients had ICANS after the first step-up dose (2.7%), 1 (0.5%) patient had ICANS after the second step-up dose and 1 (0.5%) patient had ICANS after subsequent dose(s). Recurrent ICANS occurred in 1.1% of patients. The median time to onset was 3 (range: 1 to 4) days after the most recent dose, with a median duration of 2 (range: 1 to 18) days. The most frequent clinical manifestations of ICANS included a depressed level of consciousness and Grade 1 or Grade 2 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 elranatamab-bcmm. At the first sign of neurologic toxicity, including ICANS, evaluate and treat patients immediately based on severity. Withhold or permanently discontinue elranatamab-bcmm based on severity per recommendations and consider further management per current practice guidelines.

Due to the potential for neurologic toxicity including ICANS, patients receiving elranatamab-bcmm 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 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.

Elranatamab-bcmm is available only through a restricted program under a REMS.

REMS

Elranatamab-bcmm is available only through a restricted program under a REMS called the Elrexfio REMS because of the risks of CRS and neurologic toxicity, including ICANS.

Notable requirements of the REMS include the following:

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

• Prescribers must counsel patients receiving elranatamab-bcmm about the risk of CRS and neurologic toxicity, including ICANS, and provide patients with elranatamab-bcmm Patient Wallet Card.

• Pharmacies and healthcare settings that dispense elranatamab-bcmm must be certified with the REMS program and must verify prescribers are certified through the REMS program.

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

Further information about the Elrexfio REMS program is available at www.ELREFIOREMS.com or by telephone at 1-844-923-7845.

Infections

Elranatamab-bcmm can cause severe, life-threatening, or fatal infections. In the clinical trial, in patients who received elranatamab-bcmm according to the recommended dosing schedule, serious infections, including opportunistic infections, occurred in 42% of patients, with Grade 3 or 4 infections in 31%, and fatal infections in 7%. The most common serious infections reported (≥5%) were pneumonia and sepsis.

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

Neutropenia

Elranatamab-bcmm can cause neutropenia and febrile neutropenia. In patients who received elranatamab-bcmm at the recommended dose in the clinical trial, decreased neutrophils occurred in 62% of patients, with Grade 3 or 4 decreased neutrophils in 51%. Febrile neutropenia occurred in 2.2% of patients.

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 elranatamab-bcmm based on severity.

Hepatotoxicity

Elranatamab-bcmm can cause hepatotoxicity. In the clinical trial, elevated ALT occurred in 36% of patients, with Grade 3 or 4 ALT elevation occurring in 3.8%; elevated AST occurred in 40% of patients, with Grade 3 or 4 AST elevation occurring in 6%. Grade 3 or 4 total bilirubin elevations occurred in 0.5% of patients. Liver enzyme elevation can occur with or without concurrent CRS.

Monitor liver enzymes and bilirubin at baseline and during treatment as clinically indicated. Withhold elranatamab-bcmm or consider permanent discontinuation of the drug based on severity.

Embryo-fetal Toxicity

Based on its mechanism of action, elranatamab-bcmm may cause fetal harm when administered to a pregnant woman. Advise pregnant women of the potential risk to the fetus. Advise females of reproductive potential to use effective contraception during treatment with elranatamab-bcmm and for 4 months after the last dose.

Specific Populations

Pregnancy

Based on the mechanism of action, elranatamab-bcmm may cause fetal harm when administered to a pregnant woman. There are no available data on the use of elranatamab-bcmm in pregnant women to evaluate for a drug associated risk. No animal reproductive or developmental toxicity studies have been conducted with elranatamab-bcmm. 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 the drug 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.

Elranatamab-bcmm is associated with hypogammaglobulinemia; therefore, assessment of immunoglobulin levels in newborns of mothers treated with elranatamab-bcmm 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.

Lactation

There 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 a breastfed child, advise women not to breastfeed during treatment with elranatamab-bcmm and for 4 months after the last dose.

Females and Males of Reproductive Potential

Elranatamab-bcmm may cause fetal harm when administered to a pregnant woman.

Verify the pregnancy status of females of reproductive potential prior to initiating treatment with elranatamab-bcmm.

Advise females of reproductive potential to use effective contraception during treatment and for 4 months after the last dose of elranatamab-bcmm.

Pediatric Use

The safety and effectiveness of elranatamab-bcmm in pediatric patients have not been established.

Geriatric Use

Of the 183 patients with relapsed or refractory multiple myeloma treated with elranatamab-bcmm in the MagnetisMM-3 study 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.

Common Adverse Effects

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 3 to 4 laboratory abnormalities (≥30%) are decreased lymphocytes, decreased neutrophils, decreased hemoglobin, decreased white blood cells, and decreased platelets.

General

Elranatamab-bcmm is available in the following dosage form(s) and strength(s):

Injection:

• 76 mg/1.9 mL (40 mg/mL) in a single-dose vial for subcutaneous injection.

• 44 mg/1.1 mL (40 mg/mL) in a single-dose vial for subcutaneous injection.

Dosage

It is essential that the manufacturer's labeling be consulted for more detailed information on dosage and administration of this drug. Dosage summary:

Adults

Dosage and Administration

The recommended dosing schedule for elranatamab-bcmm is provided in the following table. Initiate treatment with a step-up dosing schedule to reduce risk of cytokine release syndrome (CRS). For patients who have received at least 24 weeks of treatment with elranatamab-bcmm and have achieved a response (partial response [PR] or better) and maintained this response for at least 2 months, the dosing interval should transition to an every 2-week schedule.

• 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.

• See Full Prescribing Information for instructions on preparation and administration.

• For subcutaneous injection only.

• Administer pre-treatment medications as recommended.

• Dosage delays may be required to manage toxicities. See Full Prescribing Information for specific instructions.

• If a dose of elranatamab-bcmm is delayed, restart therapy as recommended. See Full Prescribing Information for specific instructions.