In the primary analysis of the global Phase 3 TRANSFORM study, second-line therapy with lisocabtagene maraleucel (liso-cel) significantly improved event-free survival (EFS; the primary endpoint), complete response rate (CRR), and progression-free survival (PFS), with relatively low rates of cytokine release syndrome (CRS) and neurological events (NEs), in 184 patients with primary refractory or early relapsed large B-cell lymphoma (LBCL), compared with standard-of-care (SOC) platinum-based immunochemotherapy followed when appropriate by autologous stem cell transplantation. The findings were presented at the American Society of Hematology annual meeting in December and simultaneously published online ahead of print in Blood.
After a median follow-up of 17.5 months, median EFS was not reached for liso-cel compared with 2.4 months for SOC. CRR was 74% for liso-cel versus 43% for SOC. Median PFS was also not reached for liso-cel compared with 6.2 months for SOC. Median overall survival (OS) was not significantly different between the two groups. Overall rates of CRS and NEs were 49% and 11%, respectively, with grade 3 events in 1% (CRS) and 4% (NEs).
The lack of a significant difference in OS may be due to the overall limited number of on-study patient deaths (28 in the liso-cel arm, 38 in the SOC arm) and the treatment effect of crossover, write principal investigator Jeremy S. Abramson, MD, of the Massachusetts General Hospital Cancer Center and colleagues. Sixty-six percent of SOC patients crossed over to receive liso-cel.
The TRANSFORM findings “add to recent phase 3 studies of other CAR T-cell therapies in similar second-line LBCL patient populations” and “support the use of liso-cel as a preferred second-line treatment compared with SOC for patients with primary refractory or early relapsed LBCL,” Abramson and colleagues write.
- Abramson JS, Solomon SR, Arnason JE, et al. Lisocabtagene maraleucel as second-line therapy for large B-cell lymphoma: primary analysis of phase 3 TRANSFORM study [published online ahead of print, 2022 Dec 21]. Blood. 2022;blood.2022018730. doi:10.1182/blood.2022018730