CAR T-Cell Strategy for Myeloma: Two Targets, Fewer Relapses
Posted: Monday, April 27, 2020
Does targeting B-cell maturation antigen (BCMA) plus a second antigen work better than targeting BCMA alone to mitigate BCMA escape–mediated relapse in multiple myeloma? Work conducted in mouse models by Carlos Fernandez de Larrea, MD, PhD, both of the University of Barcelona and Memorial Sloan Kettering Cancer Center, and colleagues indicate that it does. Their results were published in the journal Blood.
The second targeted antigen was G protein–coupled receptor class C group 5 member D (GPRC5D). All strategies were built on the BCMA(125)/4-1BBζ chimeric antigen receptor (CAR).
Mice with multiple myeloma had significantly longer median overall survival when treated with high-dose dual-targeting strategies versus BCMA-targeted monotherapy (not reached vs. 32 days; P < .05). Mice from both groups who survived 100 days were then injected with OPM2 BCMA CRISPR KO cells to evaluate if, and how well, latent BCMA escape–mediated relapse was prevented. Ultimately, the mice previously treated with BCMA-targeted monotherapy “succumbed to OPM2BCMA KO disease, [whereas] dual-targeted approaches prevented OPM2BCMA KO growth,” the researchers noted (the median overall survival after rechallenge, 37 days vs. not reached; P < .05).
Then, Dr. Fernandez de Larrea and colleagues sought to compare dual-targeting strategies (two parallel production and three single-vector) “to identify an optimal approach.” They concluded: “While parallel infusion of separate BCMA- and GPRC5D-targeted CAR T cells is effective, a single bicistronic vector encoding two 4-1BB-containing CARs avoids the practical challenges of parallel manufacturing and uniquely may provide superior anti–multiple myeloma efficacy.”
Disclosure: The study authors’ disclosure information can be found at ashpublications.org.