General Information

Elrexfio (elranatamab-bcmm) is a bispecific B-cell maturation antigen (BCMA)-directed CD3 T‑cell engager.

Elrexfio is specifically indicated for the treatment of 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).

Dosing/Administration

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
Elrexfio 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
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.

For subcutaneous injection only.

The recommended dosages of Elrexfio subcutaneous injection are: 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 Elrexfio and have achieved a response [partial response (PR) or better] and maintained this response for at least 2 months, the dose interval should transition to an every two-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.

Please see drug label for recommended pre-treatment medications, restarting Elrexfio after a dose delay, dose modifications and dose management of CRS and ICANS.

Mechanism of Action

Elranatamab-bcmm 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, caused proinflammatory cytokine release, and resulted in multiple myeloma cell lysis.

Side Effects

Adverse effects associated with the use of Elrexfio may include, but are not limited to, the following:

CRS

fatigue

injection site reaction

diarrhea

upper respiratory tract infection

musculoskeletal pain

pneumonia

decreased appetite

rash

cough

nausea

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.

The Elrexfio drug label comes with the following Black Box Warning: Cytokine Release Syndrome (CRS), including life-threatening or fatal reactions, can occur in patients receiving Elrexfi. Initiate treatment with Elrexfio step-up dosing schedule to reduce risk of CRS. Withhold Elrexfio until CRS resolves or permanently discontinue based on severity. Neurologic toxicity, including Immune Effector Cell-Associated Neurotoxicity Syndrome (ICANS), and serious and life-threatening reactions, can occur in patients receiving Elrexfi. 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. Elrexfio is available only through a restricted program called the Elrexfio Risk Evaluation and Mitigation Strategy (REMS).

Clinical Trial Results

FDA accelerated approval was based on data from response rates and duration of response in the single-arm Phase 2 MagnetisMM-3 trial. Data from cohort A (n=123) of the study showed meaningful responses among heavily pretreated RRMM patients who received Elrexfio as their first BCMA-directed therapy. Among the patients in this study who received four or more lines of therapy prior to Elrexfio (n=97), the overall response rate was 58%, with an estimated 82% maintaining the response for at least nine months. The median time to first response was 1.2 months. This study also established Elrexfio as the first BCMA-directed therapy in the U.S. with once-every-other-week dosing for responding patients after 24 weeks of weekly therapy. The label also includes data from cohort B (n=64). Among the 63 patients in this cohort who received at least four prior lines of therapy, including a BCMA-directed therapy (CAR-T or antibody-drug conjugate), the overall response rate was 33% after a median follow-up of 10.2 months, with an estimated 84% maintaining the response for at least nine months.

In longer-term efficacy data for cohort A (n=123), the objective response rate was 61%, and median duration of response, overall survival, and progression-free survival had not yet been reached at 14.7 months median follow-up. For the responding patients, the probability of maintaining a response at 15 months was 72%. Among responding patients who switched to every-other-week dosing at least six months prior to the data cut-off date (n=50), 80% maintained or improved their response after the switch, with 38% attaining a complete response or better after the switch.