Researchers Explore Safety and Efficacy of BCMA CAR T-Cell Therapy in Patients with Multiple Myeloma

Chimeric antigen receptor (CAR) T-cell immunotherapy has shown great promise against hematologic malignancies. Therefore, the treatment has become a robust area of current research in the fight against multiple myeloma (MM). One of the most popular areas for CAR T-cell research involves B-cell maturation antigen (BCMA). However, concerns remain about the durability of response and potential toxicities, such as cytokine release syndrome (CRS) and neurotoxicity.

A group of researchers recently sought to determine the safety and efficacy of this type of therapy, as well as factors that affect outcomes. Their findings were published in the Journal of Hematology and Oncology.

“Current evidence on BCMA-targeted CAR T-cell therapy in MM is restricted to relatively small, non-randomized early phase clinical trials. Hence, at this stage, it is difficult to obtain a clear sight on the toxicity and efficacy that can be expected from this novel therapeutic approach in relapsed/refractory MM patients,” wrote the authors, led by Gils Roex of the Laboratory of Experimental Hematology in the Vaccine and Infectious Disease Institute at the University of Antwerp in Belgium.

The team performed a search to identify clinical studies published from January 1, 2016, to January 1, 2020. Search terms included “BCMA,” “CAR,” and “multiple myeloma.” The search revealed 27 registered clinical studies that used 23 CAR T-cell products to treat 640 patients with MM.

Among all of the studies, BCMA-targeted CAR T-cell therapy produced a pooled overall response rate of 80.5% (range, 73.5%–85.9%). The rate of complete responses was 44.8% (range, 35.3%–54.6%). Median progression-free survival (PFS) was 12.2 months (range, 11.4–17.4), much longer than the published expected PFS of 1.9 months (range, 1.5–3.7).

Regarding toxicities, the review revealed that CRS occurred in 80.3% of patients (range, 69.0%–88.2%). Neurotoxicity occurred in 10.5% (range, 6.8%–16.0%). Studies that involved more heavily pretreated patients had higher rates of neurotoxicity (19.1% versus 2.8%).

Sub-analyses showed longer better durability of response with 4-1BB-based as compared to CD28-based CD19 CAR T cells. “Our results also seem to favor the use of lentiviral over retroviral vectors for CAR T-cell transduction given their superior clinical activity without increasing toxicity,” the authors wrote.

The researchers concluded that, even though BCMA-targeted CAR T-cell therapy led to significant toxicities, the treatment has been very effective thus far, even in patients with advanced MM.