Elranatamab 44mg/1.1ml solution for injection vials

Elranatamab is a humanized B-cell maturation antigen (BCMA)-CD3 bispecific antibody. In the ongoing phase 2 MagnetisMM-3 trial, patients with relapsed or refractory multiple myeloma received subcutaneous elranatamab once weekly after two step-up priming doses. After six cycles, persistent responders switched to biweekly dosing. Results from cohort A, which enrolled patients without prior BCMA-directed therapy (n = 123) are reported. The primary endpoint of confirmed objective response rate (ORR) by blinded independent central review was met with an ORR of 61.0% (75/123); 35.0% ≥complete response. Fifty responders switched to biweekly dosing, and 40 (80.0%) improved or maintained their response for ≥6 months. With a median follow-up of 14.7 months, median duration of response, progression-free survival and overall survival (secondary endpoints) have not been reached. Fifteen-month rates were 71.5%, 50.9% and 56.7%, respectively. Common adverse events (any grade; grade 3-4) included infections (69.9%, 39.8%), cytokine release syndrome (57.7%, 0%), anemia (48.8%, 37.4%), and neutropenia (48.8%, 48.8%). With biweekly dosing, grade 3-4 adverse events decreased from 58.6% to 46.6%. Elranatamab induced deep and durable responses with a manageable safety profile. Switching to biweekly dosing may improve long-term safety without compromising efficacy. ClinicalTrials.gov identifier: NCT04649359 .

Abstract licence: CC BY

Recent advances in multiple myeloma (MM) treatment, including bispecific antibodies (BsAbs), have improved outcomes. Elranatamab, a BsAb targeting B-cell maturation antigen and CD3, has shown efficacy in relapsed/refractory MM (RRMM). However, its use in patients with end-stage renal disease (ESRD) undergoing hemodialysis (HD) is not well documented, as clinical trials often exclude this population. We report a 72-year-old woman with RRMM and ESRD on HD who was successfully treated with elranatamab after multiple prior therapies. She achieved a stringent complete response with undetectable minimal residual disease. Adverse events included grade 1 cytokine release syndrome, mild hypotension, and acute cholangitis, all resolved with appropriate management. Our literature review suggests BsAbs can be effective and generally well-tolerated in RRMM patients with ESRD on HD, although infection risk warrants caution. This report highlights elranatamab as a promising option for this vulnerable population. While initial responses and safety appear favourable, further studies are required to establish long-term outcomes.

Abstract licence: CC BY-NC-ND

Multiple myeloma is the second most common plasma cell malignancy, characterized by uncontrolled proliferation of plasma cells within the bone marrow. ELREXFIO™ (elranatamab-bcmm) is a recently FDA-approved drug for relapsed and refractory multiple myeloma. The progression of multiple myeloma involves interactions with various bone marrow cell types, and targeting this microenvironment has shown promising results in inhibiting its growth and osteolysis. ELREXFIO, a bispecific antibody targeting CD3 and BCMA, activates cytotoxic T-lymphocyte responses against BCMA-expressing myeloma cells. Clinical trials, such as MagnetisMM-3, demonstrated significant response rates and long-term tolerability. Its approval offers hope to multiple myeloma patients, especially those with relapsed or refractory cases, as innovative therapies like ELREXFIO continue to improve outcomes in this challenging malignancy.

Abstract licence: CC BY-NC

BACKGROUND: Elranatamab is a heterodimeric humanized full-length bispecific antibody composed of one B-cell maturation antigen (BCMA) binding arm and one cluster of differentiation 3 (CD3) binding arm. Results from the MagnetisMM-3 study indicated deep and durable responses in patients with relapsed or refractory multiple myeloma (RRMM). OBJECTIVE: The current analysis was conducted to characterize the relationship between free (i.e., unbound) elranatamab exposure and objective response rate (ORR), complete response rate (CRR), progression-free survival (PFS), and duration of response (DOR), and the impact of potential covariates on these exposure-response (E-R) relationships. PATIENTS AND METHODS: Data from four clinical studies and a wide dosing range were used for the E-R analysis. The E-R analyses of ORR and CRR were conducted by binomial logistic regression method, whereas Kaplan-Meier (KM) curves and Cox proportional hazards (PH) model were used for PFS and DOR. RESULTS: The analysis included data from 312 response-evaluable patients. The results suggested that higher elranatamab exposure and lower soluble BCMA (sBCMA) were associated with higher probability of achieving objective response (OR) and complete response (CR). For PFS, higher exposure was associated with longer PFS, which is driven by rapid responses or progression events within the initial treatment cycles. At later time points, a flat relationship between exposure and PFS was observed. No E-R relationship was identified for DOR. CONCLUSIONS: The current analyses support the approved initial dosing regimen of elranatamab and the dosing switch to less frequent dosing in responding patients during later treatment cycles. GOV IDENTIFIERS: NCT03269136, NCT04798586, NCT04649359, and NCT05014412.

Abstract licence: CC BY-NC