Use of lisocabtagene maraleucel (liso-cel) in second-line therapy was associated with improved event-free survival (EFS) over standard of care (SOC) in treatment of patients with primary refractory or early relapsed large B-cell lymphoma (LBCL) in the phase 3 TRANSFORM study. Study results were reported in the journal Blood.
The open-label trial (ClinicalTrials.gov Identifier: NCT03575351) enrolled adult patients who were eligible for autologous stem cell transplantation (ASCT). Patients were randomly assigned 1:1 into study arms receiving either liso-cel (100×106 chimeric antigen receptor-positive T cells) or SOC platinum-based immunochemotherapy for 3 cycles, with responders then receiving high-dose chemotherapy and ASCT. Crossover was allowed from the SOC arm to the liso-cel arm.
The primary efficacy endpoint of the study was EFS, which was assessed through independent review. Key secondary endpoints included the complete response (CR) rate, progression-free survival (PFS), and overall survival (OS).
The intention-to-treat population included 92 patients in the liso-cel arm and 92 patients in the SOC arm. Patients had median ages of 60 years in the liso-cel arm and 58 years in the SOC arm, and 54% of patients in each study arm had Ann Arbor stage 4 disease.
The primary analysis of this study was conducted at a median follow-up of 17.5 months (range, 0.9-37.0). In this analysis, the median EFS duration in the liso-cel arm was not reached (95% CI, 9.5-not reached), compared with 2.4 months (95% CI, 2.2-4.9) for the SOC arm (hazard ratio [HR], 0.356; 95% CI, 0.243-0.522). The 18-month EFS rates were 52.6% (95% CI, 42.3-62.9) in the liso-cel arm and 20.8% (95% CI, 12.2-29.5) in the SOC arm. Liso-cel was also reportedly favored for EFS in all prespecified subgroups.
The liso-cel arm also had a CR rate of 74%, compared with 43% for the SOC arm (P <.0001). For the liso-cel arm, the median PFS duration was also not reached, in comparison with 6.2 months for the SOC arm (HR, 0.400; 95% CI, 0.261-0.615; P <.0001). The 18-month PFS rates were 58.2% for the liso-cel arm and 28.8% for the SOC arm.
Median OS was also not reached for the liso-cel arm, compared with 29.9 months in the SOC arm (HR, 0.724; 95% CI, 0.443-1.183; P =.0987). The 18-month OS rate for the liso-cel arm was 73.1%, and it was 60.6% for the SOC arm. In a prespecified analysis adjusted for crossover, both treatment arms had a median OS that was not reached (HR, 0.415; 95% CI, 0.251-0.686), with 18-month OS rates of 73.1% for the liso-cel arm and 54.1% for the SOC arm.
Cytokine release syndrome (CRS) was reported in 49% of patients in the liso-cel arm, with grade 3 CRS occurring in 1%. Neurological events were seen in 11% of patients in the liso-cel arm, and at grade 3 in 4%. No patients had grade 4 or 5 CRS or neurological events.
“With a median follow-up of 17.5 months, the primary analysis of the TRANSFORM study confirmed the superiority of liso-cel over SOC,” the study investigators wrote in their report.
Disclosures: This research was supported by Celgene. Please see the original reference for a full list of disclosures.
Abramson JS, Solomon SR, Amason J, et al; for the TRANSFORM Investigators. Lisocabtagene maraleucel as second-line therapy for large B-cell lymphoma: primary analysis of the phase 3 TRANSFORM study. Blood. 2023;141(14):1675-1684. doi:10.1182/blood.2022018730