Review Finds Anti-BCMA CAR T-Cell Therapy Effective in Patients With MM

A new meta-analysis of chimeric antigen receptor (CAR) T-cell therapy in patients with multiple myeloma (MM) suggests the treatment has a strong rate of efficacy and that adverse events (AEs) associated with the disease are largely manageable.

The study was published in CytoJournal.

Corresponding author Xiaoxiao Ding, MD, of China’s Taizhou University Hospital, and colleagues, said novel therapies like CAR T cells are critically important in MM, given the lack of an effective cure for the disease. They said BMCA-targeting CAR-T therapies have proven to be an exciting advancement in MM care.

“The rationale behind targeting BCMA lies in its selective expression on myeloma cells while sparing healthy tissues, making it a therapeutic target,” they wrote. “Moreover, BCMA has a crucial role in the survival and proliferation of MM cells.”

Previous studies of the therapy in refractory MM cases have led to promising results, the authors noted. However, given the lengthy and complex manufacturing process associated with CAR-T therapy, they said there remains a lack of long-term data regarding patient outcomes. Hoping to help clarify the existing research, the investigators therefore decided to undertake a systematic review and meta-analysis to evaluate the safety and efficacy of anti-BMCA CAR-T therapies in patients with MM.

The investigators identified 13 studies that met their inclusion criteria. They were published between the years 2016 and 2022, and involved a total of 252 patients. The smallest studies included just 5 patients; the largest had 57 patients. Some of the studies had incomplete outcome reporting, the authors noted.

CAR T cell therapy rendering | Image credit: AIGen - stock.adobe.com

Among 7 studies with complete data, the authors said the pooled overall response rate was 82% among 185 patients, with a median response time of 10 months in 151 patients. The complete response rate among the 185 patients was 45%, they said. Among 148 patients from 5 studies, the overall survival rate was 83%, the investigators said. In all 3 categories, the investigators said the improvements for patients with CAR T cell therapy were statistically significant.

However, they found that the 80% rate of minimal residual disease negativity among the 3 studies for which data were available did not represent a statistically significant impact.

The investigators said their findings suggest that CAR T-cell therapy is an effective tool for many patients with MM. They added the incorporation of CD28 signaling domains in the design of CARs is valuable.

“Incorporating CD28 signaling domains in CAR design enhances T-cell activation and persistence, with cytokine production sustaining the anti-tumor immune response,” they said. “These results reaffirm anti-BCMA CAR T-cell therapy’s potential to advance MM treatment significantly.”

Pooled safety data were encouraging, Ding and colleagues said. Thirty-one of the 185 pooled patients reported grade 3 or 4 cytokine release syndrome (CRS; 17%). In 4 studies with 131 patients for which neurotoxicity data were available, the pooled proportion of neurotoxicity was 22%, they said.

The investigators said it is important for physicians to take an individualized approach to administering CAR T-cell therapies to achieve optimal outcomes.

“Central to this approach is the concept of patient-centric customization, where a tailored administration of CAR T-cell doses coupled with a deep understanding of individual patient attributes and vigilant response monitoring synergistically contribute to a substantial reduction in both the likelihood and severity of neurotoxicity,” they wrote.

They added that the use of interventions like the interleukin-6 receptor agonist tocilizumab (Actemra; Genentech) can help reduce the risk of CRS.

The authors said their study was limited by significant variability in the studies with regard to dosing and follow-up periods, among other factors. They said future randomized controlled trials could help bolster these data.

Reference

Zhang J, Ding X, Ding X. Exploring the efficacy and safety of anti-BCMA chimeric antigen receptor T-cell therapy for multiple myeloma: Systematic review and meta-analysis. Cytojournal. 2024;21:13. doi:10.25259/Cytojournal_64_2023