KEY TAKEAWAYS
- The Phase 2 study assessed the effectiveness of elranatamab in treating RRMM patients who had previously undergone BCMA-targeted therapies.
- Elranatamab was effective and well-tolerated in RRMM pts with prior BCMA therapy, with no new safety issues compared to BCMA-naïve patients.
The study involved a pooled analysis of data from three different trials (MM-1, NCT03269136; MM-3, NCT04649359; MM-9, NCT05014412) and used data collected approximately 10 months after the last patient received their initial dose. The trials were conducted in Phase I and Phase II settings.
The study included relapsed and refractory multiple myeloma (RRMM) patients (pts) who had received at least one Proteasome Inhibitor (PI), one Immunomodulatory Imide Drug (IMiD), one anti-CD38 antibody, and one BCMA-directed therapy.
In the MM-1 trial with 13 participants, varying doses of subcutaneous elranatamab between 215 and 1000 µg/kg were administered. In the MM-3 (n=64) and MM-9 (n=9) trials, the prescribed Phase II dose of subcutaneous 76 mg once a week was used.
The treatment’s effectiveness was determined based on criteria set by the International Myeloma Working Group. Treatment-emergent adverse events (TEAEs) were assessed using the Common Terminology Criteria for Adverse Effects (MM-1 used version 4.03; MM-3 and MM-9 used version 5.0). The American Society for Transplantation and Cellular Therapy guidelines were followed to grade cytokine release syndrome (CRS) and immune effector cell-associated neurotoxicity syndrome (ICANS).
The study involved 86 pts, and at the time of enrollment, key characteristics were as follows: 69.8% had an Eastern Cooperative Oncology Group (ECOG) performance status of 1 or higher; 24.4% had high-risk cytogenetics; 54.7% showed extramedullary disease; and the median number of prior treatments was 7, ranging from 3 to 19. These previous treatments included BCMA-directed antibody-drug conjugates (67.4%) and chimeric antigen receptor T cells (41.9%). Additionally, 96.5% were triple-class refractory and 54.7% were penta-drug refractory.
After a median follow-up of 10.3 months, the median duration of treatment was 3.3 months. At the time of data cutoff, 24.4% of pts were still undergoing treatment, and progressive disease was the most frequent reason for discontinuation, accounting for 44.2%. The overall response rate was 45.3%, with 17.4% of pts achieving a complete response or better. The median time to attain an objective response among responders was 1.9 months. The median duration of response (DOR) had not been reached at 10 months, and the DOR rate at 9 months was 72.4%. Median progression-free survival was 4.8 months, while median overall survival was not reached by the 10-month mark.
The most common treatment-emergent adverse events (TEAEs) affecting at least 25% of pts were cytokine release syndrome (CRS) (65.1%), anemia (59.3%), neutropenia (44.2%), thrombocytopenia (40.7%), diarrhea (33.7%), and lymphopenia (32.6%). ICANS was reported in 5.8% of pts.
Elranatamab showed efficacy and was well-tolerated in pts with RRMM who had previously been treated with BCMA-targeted therapies. No new safety issues were identified compared to pts who were naive to BCMA therapies.
Source: https://clml-soho2023.elsevierdigitaledition.com/496/index.html
Clinical Trial: https://classic.clinicaltrials.gov/ct2/show/NCT04649359
Nooka, A.K., Lesokhin, A.M., Mohty, M., Niesvizky, R., Maisel, C., Arnulf, B., Larson, S.M., Varshavsky-Yanovsky, A.N., Leleu, X., Karlin, L., Vesole, D.H., Bahlis, N.J., Fernández de Larrea, C., Raje, N., Leip, E., Conte, U., Elmeliegy, M., Viqueira, A., Manier, S. Efficacy and Safety of Elranatamab by Age and Frailty in Patients With Relapsed/Refractory Multiple Myeloma (RRMM): Subgroup Analysis From MagnetisMM‑3.
