Elranatamab demonstrated substantial and enduring responses with a favorable safety profile in patients with relapsed or refractory multiple myeloma in a phase 3 trial. Transitioning to a biweekly dosing regimen could improve safety outcomes in the long term while still ensuring the maintenance of therapeutic effectiveness.
Elranatamab is a humanized bispecific antibody that targets both B-cell maturation antigen and CD3. This dual-targeting strategy activates T cells and directs them to mount an effective cytotoxic response against myeloma cells.
Patients with relapsed or refractory multiple myeloma (MM) showed promising safety and efficacy results in the MagnetisMM-1 study published in the journal Nature Medicine.
The MagnetisMM-3 study, a phase 2 trial, evaluated elranatamab monotherapy in 123 patients with relapsed or refractory multiple myeloma. Among the 123 patients who received elranatamab, the median age was 68 years (range: 36–89 years), 55.3% were male, 58.5% were White, 13% were Asian, and 7.3% were Black/African American.
Elranatamab Demonstrated a 61% Objective Response Rate
After a median follow-up of 14.7 months, the primary endpoint, objective response rate, was achieved at 61% in this cohort, with 35% attaining a complete response.
Rapid Responses and Durable Remission Rates in Multiple Myeloma Patients
The median response time in treated patients was 1.2 months, while the median response duration was unknown. The Kaplan–Meier estimate at 15 months showed a 71.5% likelihood of response maintenance in the total population and 89.2% in complete remission patients.
Prognostic Factors Elevate Response Rates to Elranatamab
Prognostic variables for increased response rates included Revised International Staging System (R-ISS) stage I–II disease, absence of extramedullary disease, and penta-refractory disease. Different subpopulations responded similarly to elranatamab.
Elranatamab Therapy Was Associated With Manageable Adverse Reactions
The administration of elranatamab therapy was generally well-tolerated, exhibiting manageable adverse reactions. Treatment-emergent adverse events (TEAEs) were documented in all patients, with grade 3 or 4 events observed in 70.7%. Hematologic TEAEs were observed at the highest frequency, with neutropenia being the predominant reason for dose reduction. Infectious diseases, including cases related to COVID-19, were the primary factor contributing to interruptions in medication administration. The vast majority of patients were able to successfully resume medical treatment after experiencing interruptions in their prescribed dosage.
Cytokine Release Syndrome in Multiple Myeloma Patients
Cytokine release syndrome (CRS) was observed in 56.3% of patients, with all occurrences being classified as grade 1 or 2. The commencement of CRS was generally observed within a span of 2 days following administration, and the majority of incidents took place during the initial doses.
Low Incidence of Immune-Related Neurotoxicity in Patients Treated With Elranatamab
Immune effector cell-associated neurotoxicity syndrome incidence was observed in 3.4% of patients, with all occurrences classified as grade 1 or 2. Supportive therapies, such as the administration of corticosteroids and tocilizumab, successfully mitigated these untoward occurrences.
Lesokhin, A. M., Tomasson, M. H., Arnulf, B., Bahlis, N. J., Miles Prince, H., Niesvizky, R., Rodrίguez-Otero, P., Martinez-Lopez, J., Koehne, G., Touzeau, C., Jethava, Y., Quach, H., Depaus, J., Yokoyama, H., Gabayan, A. E., Stevens, D. A., Nooka, A. K., Manier, S., Raje, N., Iida, S., … Mohty, M. (2023). Elranatamab in relapsed or refractory multiple myeloma: phase 2 MagnetisMM-3 trial results. Nature Medicine, 29(9), 2259–2267. https://doi.org/10.1038/s41591-023-02528-9