Prevalence of CCR7-Positive CD8 T Cells as a Prognostic Factor in B-Cell Maturation Antigen -Targeted Chimeric Antigen Receptor T Cell Therapy.

Background: Chimeric antigen receptor T (CAR-T) cell therapy is effective for relapsed or refractory multiple myeloma (RRMM); however, relapse after the B-cell maturation antigen (BCMA) CAR-T cell therapy is associated with poor outcome. Hence, appropriate biomarkers that can predict the outcome are needed.

Methods: Patients who received idecabtagene vicleucel, a BCMA-targeted CAR-T cell therapy, were divided into two groups according to a cut-off value of 180 days for the progression-free survival (PFS) event.

Results: Patients in the short responder group were older at diagnosis, had a shorter time from diagnosis to apheresis, and more frequently had prior bispecific antibody treatment or alkylator-containing chemotherapies, while they received less immunomodulatory drugs-based chemotherapy just prior to apheresis. Apheresis samples collected from the long responder group had significantly higher proportion of CD8-positive naïve or stem cell memory (CCR7CD45RO) or central memory (CCR7CD45RO) T cells. When these two T cell subsets were combined into CCR7-positive CD8 T cells, the patients with high levels of CCR7-positive CD8 T cells showed significantly better PFS.

Conclusion: In the future, our results will help us to select specific patients that are likely to have a more favorable outcome and should contribute to establishing an optimal application strategy for CAR-T cell therapies in RRMM.