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CAR T cells targeting BCMA and CD19 for newly diagnosed and relapsed multiple myeloma patients responding to current therapy

Garfall, Alfred, Cohen, Adam, Susanibar-Adaniya, Sandra, Vogl, Dan, Waxman, Adam, Lacey, Simon, Vanessa, Gonzalez, Gupta, Minnal, Kulikovskaya, Irina, Tian, Lifeng, Chen, Fang, Koterba, Natalka, Bartoszek, Chelsie, Plesa, Gabriela, Siegel, Donald, Brennan, Andrea, Nelson, Anne Marie, Ferthio, Regina, Cosey, Angela, Shea, Kim-Marie, Leskowitz, Rachel, Four, Megan, Wilson, Wesley, Miao, Fei, Eric, Lancaster, Carreno, Beatriz, Linette, Gerald, Hexner, Elizabeth, Young, Regina, Bu, Dexiu, Mansfield, Keith, Brogdon, Jennifer, June, Carl, Huang, Wei-Ting, Milone, Michael and Edward, Stadtmauer (2022) CAR T cells targeting BCMA and CD19 for newly diagnosed and relapsed multiple myeloma patients responding to current therapy. Blood Cancer Discovery.

Abstract

We conducted a phase 1 clinical trial of anti-BCMA CAR T cells (CART-BCMA) with or without
anti-CD19 CAR T cells (huCART19) in multiple myeloma (MM) patients responding to third-orlater-
(Phase A, N=10) or high-risk patients responding to first-line therapy (Phase B, N=20),
followed by early lenalidomide or pomalidomide maintenance. We observed no high-grade CRS
and only one instance of low-grade neurologic toxicity. In vivo CART-BCMA expansion was
comparable to that previously observed with CART-BCMA in relapsed/refractory MM. Early
maintenance therapy was safe and feasible and coincided with CAR T cell re-expansion and
late-onset clinical response in some patients. Pre-treatment MM cell-surface BCMA levels were
unexpectedly low despite no prior exposure to anti-BCMA therapy. Despite low disease burden
and evidence of anti-MM activity in most patients, only 4 subjects converted to complete
response. Outcomes with CART-BCMA + huCART19 were similar to CART-BCMA alone.

Item Type: Article
Keywords: Multiple myeloma, cellular immunotherapy, CAR T cell therapy, B cell maturation antigen, cytokine release syndrome
Date Deposited: 17 Dec 2022 00:45
Last Modified: 17 Dec 2022 00:46
URI: https://oak.novartis.com/id/eprint/47478

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