Update on CART-BCMA Therapy for Resistant Multiple Myeloma
Posted: Friday, August 9, 2019
Whether accompanied—or, notably, not accompanied—by lymphodepleting chemotherapy, infusions of B-cell maturation antigen–specific CAR T cells (CART-BCMA) seem to be clinically active in heavily pretreated patients with relapsed or refractory multiple myeloma, according to the results of a phase I study published in the Journal of Clinical Investigation. “Lymphodepletion is not absolutely required for robust and sustained CAR T-cell expansion,” the authors concluded, although “successful adoptive transfer of tumor-specific T cells…in humans has most commonly followed some form of lymphodepleting conditioning.”
Adam D. Cohen, MD, of Abramson Cancer Center, University of Pennsylvania, Philadelphia, and colleagues evaluated 25 patients in 3 treatment cohorts: cohort 1 received 1 × 108 to 5 × 108 CART-BCMA cells alone; cohort 2 received cyclophosphamide plus 1 × 107 to 5 × 107 CART-BCMA cells; and cohort 3 received cyclophosphamide plus 1 × 108 to 5 × 108 CART-BCMA cells. Responses were achieved in 44% (4/9), 20% (1/5), and 64% (7/11) of patients in cohorts 1, 2, and 3, respectively. These responses included five partial, five very good partial, and two complete responses, three of which were continuing at 11, 14, and 32 months.
“Responses and CART-BCMA expansion were associated with CD4/CD8 T-cell ratio and frequency of CD45RO– CD27+ CD8+ T cells in the premanufacturing leukapheresis product,” noted the team. The durability of response remains a challenge, they noted, as does disease progression during manufacturing and the potential for antigen escape due to changes in BCMA expression.
The myriad avenues for further research, suggested Dr. Cohen and his co-investigators, include “exploring less heavily pretreated/refractory patient populations, dual-antigen–targeting CAR constructs, novel lymphodepletion regimens or manufacturing protocols, and off-the-shelf CART products, [which] may further optimize the safety and long-term efficacy of this approach.”
Disclosure: The study authors’ disclosure information may be found at jci.org.