Phase 1 Trial Supports Safety and Efficacy of Novel CAR-T Therapy for Large B-cell Lymphomas
- The TRANSCEND NHL 001 trial examined the safety and activity of lisocabtagene maraleucel (liso-cel), an investigational CD19-directed chimeric antigen receptor (CAR) T-cell therapy, in adults with relapsed/refractory large B-cell lymphoma
- 344 patients underwent leukapheresis for manufacture of CAR+ T cells and 269 received at least one dose of liso-cel
- Grade greater than or equal to 3 cytokine release syndrome occurred in 2% of patients and grade greater than or equal to 3 neurological events in 10%, with no deaths due to those toxicities
- An objective response was achieved by 73% of 256 patients and 53% achieved a complete response; the 1-year duration of response rate was 55%
- Clinically meaningful activity of lisocabtagene maraleucel was noted in patients with uncommon histological subtypes and those with characteristics of poor prognosis
CD19-directed chimeric antigen receptor T-cell (CAR T) therapy has been a breakthrough treatment for large B-cell lymphoma, associated with high response rates and durable remission. An investigational CAR T product, lisocabtagene maraleucel (liso-cel), has unique features including defined composition of CD4+:CD8+ CAR T-cells.
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Jeremy Abramson, MD, of the Massachusetts General Hospital Cancer Center, and colleagues observed promising results of liso-cel in patients with a wide range of large B-cell lymphoma subtypes, most of whom had poor prognosis. They report preliminary data from the phase seamless design pivotal 1 TRANSCEND NHL 001 trial in The Lancet.
TRANSCEND, conducted at 14 U.S. cancer centers, combined dose finding, dose expansion and dose confirmation. 344 adults underwent leukapheresis for manufacture of CAR+ T cells between January 11, 2016 and July 5, 2019, and 269 received at least one dose of liso-cel. Three target doses were tested sequentially.
The cutoff for this analysis was August 12, 2019. Safety data were combined across dose levels because toxicity was apparently not dose-related. The most common grade ≥3 treatment-emergent adverse events were neutropenia (60% of patients), anemia (37%) and thrombocytopenia (27%). Grade ≥3 febrile neutropenia occurred in 9%.
Of seven deaths, four were considered related to liso-cel and lymphodepleting chemotherapy. Grade ≥3 cytokine release syndrome occurred in 2% of patients and grade ≥3 neurological events in 10%, with no deaths due to those toxicities.
256 patients were evaluable for efficacy:
- Objective response–73%
- Complete response—53%
- Median time to response—1 month
- 1-year duration of response—55%
- 1-year progression-free survival—44%
- 1-year overall survival—58%
Responses were observed across all histological subtypes and poor-prognostic features. Follow-up of TRANSCEND is ongoing and is expected to guide real-world care of patients with understudied subtypes of large B-cell lymphoma.
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