ZUMA-7 results
THE ZUMA-7 trial randomly assigned 180 patients to receive CAR T-cell therapy with axi-cell and 179 patients to standard of care. This consisted of two or three cycles of investigator-selected, protocol-defined chemoimmunotherapy, with patients who had a complete or partial response going onto ASCT.
As noted, the primary endpoint of EFS according to blinded central review favored axi-cel, with 24-month event-free survival rates of 41% vs. 16% for standard of care. The difference translated into a hazard ratio (HR) for progression or death of 0.40 (P < .001).
In all, 65% of patients had a complete response (CR) to axi-cel, compared with 32% with standard of care. The respective overall response rates were 83% and 50% (P < .001).
Dr. Locke pointed out that 94% of the patients assigned to axi-cel received definitive therapy, compared with the 36% of patients in the standard-of-care arm who went on to ASCT.
In an interim analysis, 2-year estimated overall survival was 61% with axi-cel vs. 52% with standard of care, although this difference was not statistically significant.
Median overall survival was not reached with axi-cel, compared with 35.1 months with standard-of-care.
Grade 3 or higher adverse events occurred in 91% of patients with CAR T, and 83% with the standard of care. In the axi-cel arm, 6% of patients had grade 3 or higher cytokine release syndrome (CRS), and 21% had grade 3 or higher neurologic events, although there were no deaths related to CRS or neurologic events.
TRANSFORM results
The TRANSFORM trial had broader eligibility criteria than ZUMA-7, including patients who had diffuse LBCL not otherwise specified (de novo or transformed from indolent NHL), high-grade BCL (double- or triple-hit) with DLBCL histology, follicular lymphoma grade 3B, primary mediastinal LBCL, or T-cell/histocyte-rich LBCL.
A total of 184 patients were randomly assigned, 92 in each group, to receive either liso-cel or standard-of-care. Patients assigned to liso-cel were allowed to have bridging therapy, and crossover to liso-cel was allowed for patients assigned to standard of care who either did not have a response by week 9 after randomization, had disease progression at any time, or started a new antineoplastic therapy after ASCT.
As noted before, the primary endpoint of EFS significantly favored CAR T-cell therapy, with a hazard ratio of 0.349 (P < .0001).
The EFS rates at 6 months were 63.3% with liso-cel vs 33.4% with standard of care, and the EFS rates at 12 months were 44.5% vs. 23.7%, respectively.
“Overall survival data were still immature at the time of this analysis, but show a trend favoring liso-cel, despite crossover,” Dr. Kamdar said.
Grade 3 or higher adverse events (AEs) occurred in 92% of patients on liso-cell and 87% of patients on standard of care. There was one treatment-related death in the liso-cel arm, and two in the standard of care arm, both from grade 3 or higher AEs. Neutropenia, anemia, and thrombocytopenia were the most common treatment-emergent AEs in each group.
ZUMA-7 is supported by Kite. Dr. Locke disclosed serving as a scientific advisor to Kite and relationships with other companies. TRANSFORM is supported by Celgene (BMS). Dr. Kamdar disclosed consultancy fees from BMS and others.
A version of this article first appeared on Medscape.com.