Elranatamab-bcmm Approved for Adult Patients With Relapsed or Refractory Multiple Myeloma

Novel drug product elranatamab-bcmm (Elrexfio) was granted accelerated FDA approval on August 14, 2023, for the treatment of adult patients with relapsed or refractory multiple myeloma who have received at least 4 prior lines of therapy including a proteasome inhibitor (PI), an immunomodulatory agent (IMiD), and an anti-CD38 monoclonal antibody.¹

The drug is a 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 cause proinflammatory cytokine release and result in multiple myeloma cell lysis. It has a black box warning for cytokine release syndrome (CRS) and neurologic toxicities including immune effector cell–associated neurotoxicity syndrome (ICANS).

Efficacy

MagnetisMM-3 (NCT04649359) is an open label, single arm, multicenter study² that evaluated elranatamab-bcmm therapy in patients with relapsed or refractory multiple myeloma. The study included patients who were refractory to at least 1 PI, 1 IMiD, and 1 anti-CD38 monoclonal antibody. A total of 123 patients naive to prior BCMA-directed therapy (pivotal cohort A) and 64 patients with prior BCMAdirected antibody-drug conjugate (ADC) or chimeric antigen receptor (CAR) T-cell therapy (supportive cohort B) were included in the trial. Efficacy was based on objective response rate (ORR) and duration of response (DOR).

In pivotal cohort A, the median time to first response was 1.22 months (range, 0.9-6.5 months). With a median follow-up of 11.1 months among responders, the DOR rate at 6 months was 90.4% and at 9 months was 82.3%. In the supportive cohort B group, ORR was 33.3%. After a median follow-up of 10.2 months (range, 9.9-11 months), median DOR was not reached and the DOR rate at 9 months was 84.3%.

Safety

Elranatamab-bcmm causes release of cytokines that may suppress the activity of cytochrome P450 (CYP) enzymes, leading to increased exposure to CYP substrates, which may lead to serious adverse reactions. Thus, monitoring drug concentrations of CYP substrates and signs of toxicities while on elranatamab-bcmm is important. The most common adverse reactions (> 20%) reported from the trial were predominantly immune-related effects including CRS, fatigue, injection site reactions, diarrhea, upper respiratory tract infections, musculoskeletal pain, pneumonia, decreased appetite, rash, cough, nausea, and pyrexia.

READ MORE: Assessing B-Cell Maturation Antigen Directed Therapies in Multiple Myeloma Treatment

Some grade 3 and grade 4 laboratory abnormalities (≥ 30%) were noted, including a decrease in lymphocytes, neutrophils, hemoglobin, white blood cells, and platelets. Other clinically relevant adverse reactions in less than 10% of patients who received elranatamab-bcmm were ICANS, febrile neutropenia, Guillain-Barre syndrome, abdominal pain, acute kidney injury, COVID-19, cardiac failure, congestion, and thrombosis.

Dosing and Administration

The recommended dosing schedule for elranatamab-bcmm subcutaneous injection is as follows: step-up dose 1 of 12 mg on day 1, step-up dose 2 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 elranatamab-bcmm and have achieved a response (partial response or better) and maintained this response for at least 2 months, the dose interval should transition to an every-2-week schedule.

Pretreatment medications are required with each step-up and maintenance dose of elranatamab-bcmm; those medications include oral acetaminophen 650 mg, oral or intravenous dexamethasone 20 mg, and oral diphenhydramine 25 mg. There were no significant diferences in the pharmacokinetics of elranatamabbcmm observed in either renal or hepatic impairment.

Feryal Alhamadani, PharmD, is a PGY-1 pharmacy resident at John Dempsey Hospital/ UConn Health, Farmington, Connecticut. Kevin W. Chamberlin, PharmD, FASCP, is the associate vice president and chief pharmacy ofcer at John Dempsey Hospital/UConn Health, Farmington, Connecticut.

READ MORE: Oncology Resource Center

References

1. Elrexfio.Prescribing information. Pfizer; August 2023. https://www.accessdata.fda.gov/drugsatfda_docs/label/2023/761345s000lbl.pdf 

2. Lesokhin AM, Tomasson MH, Arnulf B, et al. Elranatamab in relapsed or refractory multiple myeloma: phase 2 MagnetisMM-3 trial results. Nat Med. 2023;29(9):2259-2267. doi:10.1038/s41591-023-02528-9