Phase 1 Study Outcomes of CAR T-Cell Therapy for Relapsed Multiple Myeloma

Exploring additional targets for CAR T-cell therapy

Dr. Susan Bal presents the interim results of a phase one multi-center, open-label study evaluating the clinical activity of BMS 986393, a GPRC5D-directed autologous CAR T-cell therapy, in patients with relapsed refractory multiple myeloma. The study aimed to target B-cell maturation antigen (BCMA) and explore additional targets for CAR T-cell therapy. The results showed a favorable safety profile with manageable toxicities, primarily hematologic. Cytokine release syndrome (CRS) and immune effector cell-associated neurotoxicity syndrome (ICANS) were observed but mostly low-grade and reversible. The overall response rate was 86.5%, with a complete response rate of 38.5% across all dose levels. Responses were also observed in patients who had prior BCMA-directed therapy. The preliminary data supports BMS-986393 as a potential treatment option for relapsed myeloma patients, regardless of their prior BCMA-directed therapy status.

• BMS-986393 is a GPRC5D-directed autologous CAR T-cell therapy.
• The study aimed to target B-cell maturation antigen (BCMA) and explore additional targets for CAR T-cell therapy.
• Sixty-seven patients with relapsed refractory multiple myeloma were treated in the study.
• Eligible patients had at least three prior lines of treatment, including a proteasome inhibitor, an immunomodulatory agent, and a CD38 molecule antibody.
• Most patients (78%) on the study were triple-class refractory.
• The maximum tolerated dose was not exceeded.
• Most grade 3 and 4 toxicities were primarily hematologic, consistent with CAR T-cell therapy in relapsed myeloma.
• Cytokine release syndrome (CRS) occurred in 87% of patients, mostly low-grade, with a median duration of four days.
• Immune effector cell-associated neurotoxicity syndrome (ICANS) occurred in 10% of patients, mostly low-grade, and reversible.
• High-grade infections occurred in about 15% of the subjects.
• Soluble BCMA, a marker of tumor burden, was decreased at all dose levels.
• The overall response rate was 86.5%, with a complete response rate of 38.5% across all dose levels.
• Responses were observed in patients who had prior BCMA-directed therapy.
• Pharmacokinetic analysis showed fast expansion and multi-phasic decline following IV infusion.
• Further development planning for BMS-986393 is ongoing.

Authors:
Susan Bal, Jesus Berdeja, Myo Htut, Mehmet Kocoglu, Tara Gregory, Larry D. Anderson, Adriana Rossi, Daniel Egan, Luciano Costa, Lisa Kelly, Safiyyah Ziyad, Hongxiang Hu, Yanping Chen, Allison J. Kaeding, Michael Burgess,  Kristen Hege, Omar Nadeem