Details

Autor(en) / Beteiligte

• Cohen, Adam D
• Garfall, Alfred L
• Stadtmauer, Edward A
• Melenhorst, J Joseph
• Lacey, Simon F
• Lancaster, Eric
• Vogl, Dan T
• Weiss, Brendan M
• Dengel, Karen
• Nelson, Annemarie
• Plesa, Gabriela
• Chen, Fang
• Davis, Megan M
• Hwang, Wei-Ting
• Young, Regina M
• Brogdon, Jennifer L
• Isaacs, Randi
• Pruteanu-Malinici, Iulian
• Siegel, Don L
• Levine, Bruce L
• June, Carl H
• Milone, Michael C

Titel

B cell maturation antigen-specific CAR T cells are clinically active in multiple myeloma

Ist Teil von

• The Journal of clinical investigation, 2019-06, Vol.129 (6), p.2210-2221

Ort / Verlag

United States: American Society for Clinical Investigation

Erscheinungsjahr

2019

Quelle

MEDLINE

Beschreibungen/Notizen

• Chimeric antigen receptor (CAR) T cells are a promising therapy for hematologic malignancies. B-cell maturation antigen (BCMA) is a rational target in multiple myeloma (MM). 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: 1) 1-5 x 108 CART-BCMA cells alone; 2) Cyclophosphamide (Cy) 1.5 g/m2 + 1-5 x 107 CART-BCMA cells; and 3) Cy 1.5 g/m2 + 1-5 x 108 CART-BCMA cells. No pre-specified BCMA expression level was required. 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 CRS and encephalopathy. Responses (based on treated subjects) were seen in 4/9 (44%) in cohort 1, 1/5 (20%) in cohort 2, and 7/11 (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 pre-manufacturing leukapheresis product. CART-BCMA infusions with or without lymphodepleting chemotherapy are clinically active in heavily-pretreated MM patients. NCT02546167. University of Pennsylvania-Novartis Alliance and NIH.