CAR T-cell Therapies Show Promise in Relapsed Multiple Myeloma

Key Insights

• Allogeneic BCMA CAR T-cell therapy demonstrates promising efficacy and reasonable safety in relapsed multiple myeloma, utilizing CRISPR technology to mitigate graft-versus-host disease.
• A clinical trial targeting GPRC5D shows high efficacy in patients who have relapsed after BCMA-targeted therapy, potentially offering a more favorable treatment option.
• The allogeneic approach allows for faster treatment delivery using "off-the-shelf" cells, addressing a key limitation of autologous CAR T-cell therapies.

Two new CAR T-cell therapy trials are showing encouraging preliminary results for patients with relapsed multiple myeloma. These trials, focusing on novel approaches to CAR T-cell therapy, offer potential new options for patients who have exhausted other treatment avenues. Ehsan Malek, MD, Director of Multiple Myeloma Translational Research at Roswell Park Comprehensive Cancer Center, highlighted the promise of these therapies.

Allogeneic BCMA CAR T-cell Therapy

One of the trials involves an allogeneic BCMA CAR T-cell therapy. This approach uses "off-the-shelf" cells instead of the patient’s own cells, significantly reducing the time required to initiate treatment. The cells are modified using CRISPR technology to remove the genes responsible for graft-versus-host disease (GVHD), a major complication of allogeneic therapies. According to Dr. Malek, the early results demonstrate "very promising" efficacy and a "very reasonable" safety profile. This is particularly significant as it addresses a key limitation of autologous CAR T-cell therapies, which require a lengthy manufacturing process using the patient's own cells.

GPRC5D-Targeted Therapy

The second trial targets GPRC5D, a protein highly expressed in multiple myeloma cells but largely absent from normal tissues. This trial is designed for patients who have relapsed after BCMA-targeted therapy. GPRC5D presents a highly selective target, potentially minimizing off-target toxicities. Preliminary data suggests high efficacy, positioning this treatment as a potentially more favorable option for patients with relapsed multiple myeloma. The selective toxicity of targeting GPRC5D on multiple myeloma cells is a key advantage.

Impact on Minority Populations

Dr. Malek also noted that the allogeneic BCMA CAR T-cell therapy is showing high efficacy among minority patients. These populations are often under-represented in clinical trials, making this finding particularly important. The ability to provide effective treatment options for diverse patient populations is a critical consideration in cancer research and treatment.