Towards a New Frontier in CAR T-Cell Therapy

Chimeric antigen receptor (CAR) T-cell therapy is an effective option for relapsed B-cell lymphoma, but access to treatment may be limited due to rapid disease progression, the time required for CAR T-cell manufacture, and geographic barriers for patients needing management at specialized centers. Investigators now report a novel CD19-targeted natural killer (NK) cell CAR (FT596) derived from an allogeneic induced pluripotent stem cell that was engineered to include an immunoglobulin Fc receptor (CD16), to enhance tumor cell targeting when co-administered with rituximab, and an interleukin-15 ligand/receptor fusion protein, to mitigate the need for exogenous cytokine support.

The industry-sponsored, multicenter, phase 1 trial tested multiple FT596 cell dose levels administered with or without rituximab to 86 patients with relapsed or refractory B-cell lymphomas, including 33 who had received prior autologous CAR T-cell therapy. Thirty-nine patients received a second dose of FT596. Toxicities included grade 1–2 cytopenias, with only one dose-limiting toxicity (thrombocytopenia). Ten patients had grade 1–2 cytokine release syndrome, and none had neurotoxicity or graft-versus-host disease. There were no FT596-related adverse events that caused treatment discontinuation or death.

All 13 patients with follicular lymphoma responded, including 85% complete remissions (CR); a third of the 32 patients with large B-cell lymphoma responded, 25% achieved CR. Responses also were achieved in other B-cell lymphoma subtypes and in 30% of patients who had received prior CAR T-cell therapy. With a median follow-up of 26 months, no patient in CR had experienced disease progression.