Dr Bal on Sequencing Considerations for BMCA- and GPRC5D-Targeted Agents in Multiple Myeloma

Susan Bal, MD, assistant professor, Hematology, Medical Oncology, University of Alabama at Birmingham (UAB), UAB Health, O’Neal Comprehensive Cancer Center, discusses questions remaining regarding sequencing of treatments in later lines for patients with relapsed/refractory multiple myeloma.

At the 2023 EHA Congress, Bal presented updated safety and efficacy data from the dose-escalation and dose-expansion portions of a phase 1 trial (NCT04674813) of the GPRC5D-targeted autologous CAR T-cell therapy BMS-986393 (CC-95266) in patients with relapsed/refractory multiple myeloma.

As agents directed at GPRC5D and other novel targets beyond BMCA are developed, sequencing of agents will need to be addressed in the treatment of this patient population, Bal begins. GPRC5D and BCMA expression are independent of each other, and beyond the different developmental timelines for different agents, BCMA-targeted agents may not necessarily need to be used first, she explains. 

Bal shares that she believes that GPRC5D-targeted agents could proceed BCMA-directed therapy. This is due to reports of lower rates of high-grade infections, both in data for the CD3/GPRC5D bispecific antibody talquetamab and early data for BMS-986393, she emphasizes. With BMS-986393, investigators have also seen a lower rate of skin and nail toxicities, she continues.

Although GPRC5D-directed therapies are still relatively new in development, these agents could eventually proceed BCMA-directed therapy, Bal says. However, there are still questions to be answered regarding potential sequencing or potential combination approaches with BCMA- and GPRC5D-targeted agents, Bal emphasizes. Notably, promising data were derived from the phase 1/2 RedirecTT-1 study (NCT04586426) evaluating talquetamab in combination with the CD3/BMCA bispecific antibody teclistamab-cqyv (Tecvayli), particularly in patients with high-risk characteristics, such as those with extramedullary plasmacytoma, she says. There have been unprecedented response rates in that cohort of patients who received talquetamab plus teclistamab, she concludes.