[HTML][HTML] B cell maturation antigen–specific CAR T cells are clinically active in multiple myeloma
AD Cohen, AL Garfall, EA Stadtmauer… - The Journal of …, 2019 - Am Soc Clin Investig
The Journal of clinical investigation, 2019•Am Soc Clin Investig
BACKGROUND. CAR T cells are a promising therapy for hematologic malignancies. B cell
maturation antigen (BCMA) is a rational target in multiple myeloma (MM). METHODS. We
conducted a phase I study of autologous T cells lentivirally transduced with a fully human,
BCMA-specific CAR containing CD3 ζ and 4-1BB signaling domains (CART-BCMA), in
subjects with relapsed/refractory MM. Twenty-five subjects were treated in 3 cohorts as
follows: cohort 1, 1× 108 to 5× 108 CART-BCMA cells alone; cohort 2, cyclophosphamide …
maturation antigen (BCMA) is a rational target in multiple myeloma (MM). METHODS. We
conducted a phase I study of autologous T cells lentivirally transduced with a fully human,
BCMA-specific CAR containing CD3 ζ and 4-1BB signaling domains (CART-BCMA), in
subjects with relapsed/refractory MM. Twenty-five subjects were treated in 3 cohorts as
follows: cohort 1, 1× 108 to 5× 108 CART-BCMA cells alone; cohort 2, cyclophosphamide …
BACKGROUND. CAR T cells are a promising therapy for hematologic malignancies. B cell maturation antigen (BCMA) is a rational target in multiple myeloma (MM).
METHODS. We conducted a phase I study of autologous T cells lentivirally transduced with a fully human, BCMA-specific CAR containing CD3ζ and 4-1BB signaling domains (CART-BCMA), in subjects with relapsed/refractory MM. Twenty-five subjects were treated in 3 cohorts as follows: cohort 1, 1 × 108 to 5 × 108 CART-BCMA cells alone; cohort 2, cyclophosphamide (Cy) 1.5 g/m2 plus 1 × 107 to 5 × 107 CART-BCMA cells; cohort 3, Cy 1.5 g/m2 plus 1 × 108 to 5 × 108 CART-BCMA cells. No prespecified BCMA expression level was required.
RESULTS. CART-BCMA cells were manufactured and expanded in all subjects. Toxicities included cytokine release syndrome and neurotoxicity, which were grade 3–4 in 8 (32%) and 3 (12%) subjects, respectively, and reversible. One subject died at day 24 from candidemia and progressive myeloma, following treatment for severe cytokine release syndrome and encephalopathy. Responses (based on treated subjects) were seen in 4 of 9 (44%) in cohort 1, 1 of 5 (20%) in cohort 2, and 7 of 11 (64%) in cohort 3, including 5 partial, 5 very good partial, and 2 complete responses, 3 of which were ongoing at 11, 14, and 32 months. Decreased BCMA expression on residual MM cells was noted in responders; expression increased at progression in most. 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.
CONCLUSION. CART-BCMA infusions with or without lymphodepleting chemotherapy are clinically active in heavily pretreated patients with MM.
TRIAL REGISTRATION. NCT02546167.
FUNDING. University of Pennsylvania-Novartis Alliance and NIH.
The Journal of Clinical Investigation