Author: By Lynda Williams, Senior medwireNews Reporter
medwireNews: The TRANSFORM study has achieved a significant improvement in event-free survival (EFS) with second-line lisocabtagene maraleucel (liso-cel) versus standard care when given to patients with relapsed or refractory large B-cell lymphoma (LBCL).
Manali Kamdar, from the University of Colorado Cancer Center in Denver, USA, explained to delegates at the 63rd American Society of Hematology Annual Meeting & Exposition in Atlanta, Georgia, USA, that only a quarter of patients achieve durable remission with salvage immunochemotherapy and haematopoietic stem-cell transplantation (HSCT).
The phase III trial assessed the CD19-directed chimeric antigen receptor (CAR) T-cell therapy liso-cel among patients with aggressive diffuse (D)LBCL, high-grade BCL, primary mediastinal LBCL, T-cell/histiocyte-rich LBCL or follicular lymphoma grade 3B.
The patients had disease that was refractory to, or had relapsed within 12 months of first-line treatment with anthracycline-based chemotherapy and a CD20-targeted agent, and were eligible for HSCT.
The patients were randomly assigned to receive liso-cel with optional bridging therapy or to receive three cycles of chemotherapy followed by HSCT where feasible.
The primary endpoint of EFS was defined as time to death, progressive disease, receipt of a new antineoplastic treatment or failure to achieve a complete response (CR) or partial response (PR) within 9 weeks of randomisation to treatment.
Median EFS at this prespecified interim analysis was 10.1 months with liso-cel versus 2.3 months with standard care, giving a significant hazard ratio for an event of 0.349 in favour of the CAR T-cell therapy, the presenter said.
This was accompanied by significant improvements with liso-cel therapy versus standard care for the secondary endpoints of complete response rate (66 vs 39%) and progression-free survival (median, 14.8 vs 5.7 months, HR=0.406). Overall survival after a median 6.2 months of follow-up is yet to mature but shows a numerical trend towards an improvement with liso-cel over standard care, with median values of unreached and 16.4 months, the presenter reported.
Manali Kamdar also said that lis-cel had “a manageable safety profile with very low rates of severe cytokine release syndrome [CRS] and neurological events” and that there were “no new safety signals”.
Specifically, 49% of patients experienced CRS and all cases were grade 1 except for one grade 3 episode. Neurological adverse events occurred in 12% of patients including grade 3 episodes in 4% but no grade 4 or 5 cases.
“Compared with the [standard of care], liso-cel demonstrated highly statistically significant and clinically meaningful improvements” in outcomes, the presenter summarised.
She concluded that liso-cel “represents a potential new second-line treatment for patients with [refractory/relapsed] LBCL where a high unmet need exists.”
Kamdar M, Solomon SR, Arnason JE, et al. Lisocabtagene maraleucel (liso-cel), a CD19-directed chimeric antigen receptor (CAR) T cell therapy, versus standard of care (SOC) with salvage chemotherapy (CT) followed by autologous stem cell transplantation (ASCT) as second-line (2L) treatment in patients (Pts) with relapsed or refractory (R/R) large B-cell lymphoma (LBCL): Results from the randomized phase 3 Transform study. Abstract 91; 63rd American Society of Hematology Annual Meeting & Exposition; Atlanta, Georgia, USA: 11–14 December 2021
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