Dr Bal on the Safety Profile of BMS-986393 in R/R Multiple Myeloma

Susan Bal, MD, assistant professor, Hematology, Medical Oncology, University of Alabama at Birmingham (UAB), UAB Health, O’Neal Comprehensive Cancer Center, discusses the toxicity profile of the GPRC5D-targeted autologous CAR T-cell therapy BMS-986393 (CC-95266) in relapsed/refractory multiple myeloma, according to findings from a phase 1 trial (NCT04674813).

This multicenter, open-label study aimed to determine the safety, maximum-tolerated dose, and recommended phase 2 dose of BMS-986393 in patients with relapsed/refractory disease who had been previously exposed to 3 or more lines of therapy. A total of 67patients enrolled on the study. Patients in the dose-escalation portion received one of the 5 dose levels ranging from 25 x 106 CAR T cells to 450 x 106 CAR T cells. Patients in the dose-expansion phase were given the agent at dose levels of either 150 x 106 CAR T cells, 300 x 106 CAR T cells, or 450 x 106 CAR T cells.

Safety analysis revealed that the majority of adverse effects (AE) observed with BMS-986393 were hematologic, Bal begins. Grade 3/4 AEs were observed in 83.6% of patients and included neutropenia (59.7%), anemia (31.3%), thrombocytopenia (29.9%), and leukopenia (22.4%). This was expected based on the safety profile of other CAR T-cell agents in this space. As GPRC5D is expressed in skin and keratinized tissue, 20.9% of patients experienced skin toxicity, 17.9% experienced dysgeusia, 9% had nail toxicity, and 1.5% had dysphagia. All of these on-target treatment-related AEs were grade 1/2. Importantly, 76.7% of patients did not require interventions for these toxicities, indicating that the regimen has a favorable safety profile, Bal notes.

Treatment-emergent cytokine release syndrome occurred in 86.6% of the patients but was predominantly low grade, Bal continues. Additionally, 10.4% of patients experienced low-grade immune effector cell-associated neurotoxicity syndrome (ICANS)-type neurotoxicity, which was ultimately reversible with and without corticosteroid treatment, she reports.

One patient experienced grade 3 dizziness, which improved to grade 2 dizziness by the data cutoff of March 23, 2023, Bal adds. Lastly, there was a low incidence of other neurotoxicity such as ataxia (3%) or paresthesia (1.5%). Although these were both low grade, it is important to be cognizant of their association with this regimen, Bal says. Continued monitoring of this and other AEs will help improve understanding of the agent’s risk/benefit profile in the relapsed/refractory space, she concludes.