Anti-BCMA/CD19 CAR T cells with early immunomodulatory maintenance for multiple myeloma responding to initial or later-line therapy.

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- or later- line therapy (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. Among 15 subjects with measurable disease, 10 exhibited PR or better; among 26 subjects responding to prior therapy, 9 improved their response category and 4 converted to MRD-negative CR/sCR. Early maintenance therapy was safe, feasible, and coincided in some patients with CAR T cell re-expansion and late-onset, durable clinical response. Outcomes with CART-BCMA + huCART19 were similar to CART-BCMA alone. Collectively, our results demonstrate favorable safety, pharmacokinetics, and antimyeloma activity of dual-target CAR T cell therapy in early lines of multiple myeloma treatment.