Phase 1 Trial Supports Safety and Efficacy of Novel CAR-T Therapy for Large B-cell Lymphomas
Key findings
- 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.
Study Details
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.
Safety
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.
Efficacy
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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