Journal Article

Elranatamab in relapsed or refractory multiple myeloma: phase 2 MagnetisMM-3 trial results

Leip, Eric, Raje, Noopur, Searle, Emma, Gabayan, Afshin Eli, Lesokhin, Alexander M., Niesvizky, Ruben, Viqueira, Andrea, Stevens, Don A., Miles Prince, H., Sullivan, Sharon T., Koehne, Guenther, Conte, Umberto, Rodrίguez-Otero, Paula, Martinez-Lopez, Joaquin, Depaus, Julien, Elmeliegy, Mohamed, Yokoyama, Hisayuki, Nooka, Ajay K., Raab, Marc-Steffen, Tomasson, Michael H., Manier, Salomon, Touzeau, Cyrille, Jethava, Yogesh, Iida, Shinsuke, Mohty, Mohamad, Quach, Hang, Czibere, Akos, Arnulf, Bertrand, Bahlis, Nizar J.

2023

Overview

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 . In a pivotal phase 2 trial, elranatamab, a bispecific antibody targeting B-cell maturation antigen (BCMA) and CD3, had a confirmed objective response rate of 61% in patients with relapsed or refractory multiple myeloma who had not previously received BCMA-directed therapy.

• Publisher: Nature Publishing Group US,Nature Publishing Group
• Subject: 631/67/1990/804 / 692/308/153 / 692/699/67/1059/2325 / 692/699/67/1990/804 / Adverse events / Anemia / Antibodies / Antigens / B-Cell Maturation Antigen / Biomedical and Life Sciences / Biomedicine / Bispecific antibodies / Cancer Research / CD3 antigen / Dosage / Humans / Infectious Diseases / Life Sciences / Lymphocytes B / Maturation / Metabolic Diseases / Molecular Medicine / Multiple myeloma / Multiple Myeloma - drug therapy / Neurosciences / Neutropenia / Priming / Progression-Free Survival / Remission Induction / Response rates / Safety management / Survival