TRANSFORM Primary Analysis Revealed Improved Outcomes with Liso-cel in the 2L Treatment of Primary Refractory or Early Relapsed LBCL

Lisocabtagene maraleucel (liso-cel) is an autologous, CD19-directed, 4-1BB chimeric antigen receptor T-cell therapy. Results of a prespecified interim analysis of the phase 3 TRANSFORM study (NCT03575351), with a median follow-up of 6.2 months (mo), had previously demonstrated superior efficacy of liso-cel versus standard of care (SOC) as a second-line (2L) treatment for patients with primary refractory or early relapsed large B-cell lymphoma (LBCL).¹ TRANSFORM primary analysis data, at a median follow-up of 17.5 mo, were first presented at the 64th American Society of Hematology Annual Meeting and Exposition, and have since been published in Blood.^1,2

Study-eligible patients were aged 18-75 years and were candidates for high-dose chemotherapy (HDCT) who had primary refractory or early relapsed (≤12 mo after first-line therapy) LBCL. All patients underwent leukapheresis prior to randomization. Patients in the SOC arm received 3 cycles of platinum-based chemotherapy, with responders proceeding to HDCT plus autologous stem-cell transplant. Crossover to receive liso-cel was allowed for patients in the SOC arm if standard therapy failed. Patients in the liso-cel arm could receive up to 1 cycle of bridging therapy at the treating investigator’s discretion. The primary end point was event-free survival (EFS) by independent review committee (IRC) assessment. Key secondary end points included IRC-assessed complete response (CR) rate, progression-free survival (PFS), and overall survival (OS).

A total of 184 patients were randomized, 92 in each arm. At baseline, 33% of patients were aged ≥65 years, 64% had diffuse LBCL (55% not otherwise specified, 8% transformed from indolent lymphomas), 23% had high-grade B-cell lymphoma (double/triple-hit), and 73% were primary refractory to first-line therapy. Median (m) EFS was not reached (NR; 95% confidence interval [CI], 9.5-NR) for liso-cel versus 2.4 mo (95% CI, 2.2-4.9) for SOC (hazard ratio [HR], 0.356; 95% CI, 0.243-0.522). The 18-mo EFS rate was 52.6% (95% CI, 42.3-62.9) for liso-cel versus 20.8% (95% CI, 12.2-29.5) for SOC. The CR rate was 74% for liso-cel versus 43% for SOC (P <.0001), and mPFS was NR (95% CI, 12.6-NR) for liso-cel versus 6.2 mo (95% CI, 4.3-8.6) for SOC (P <.0001). mOS favored liso-cel versus SOC but did not meet statistical significance: NR (95% CI, 29.5-NR) versus 29.9 mo (95% CI, 17.9-NR; HR, 0.724; 95% CI, 0.443-1.183; P = .0987). The 18-mo OS rate was 73.1% (95% CI, 63.9-82.3) for liso-cel versus 60.6% (95% CI, 50.2-71.1) for SOC. Of 26 patients with a best overall response of partial response at the interim analysis, the response converted to CR for 9 patients at the primary analysis (6/18, liso-cel; 3/8, SOC). Of 92 patients in the SOC arm, 61 (66%) experienced treatment failure and were approved for crossover to receive liso-cel. Serious treatment-emergent adverse events (SAEs) were reported in 44 (48%) and 45 (49%) patients in the liso-cel and SOC arms, respectively, with deaths due to SAEs reported in 2 patients (2%) in each arm. In both arms, disease progression was the most frequent cause of death. Safety results were consistent with previous findings.

The primary analysis of TRANSFORM confirmed the clinical benefit of liso-cel over SOC, with significant improvements in EFS, CR rate, and PFS, reinforcing liso-cel as a preferred 2L treatment for patients with primary refractory or early relapsed LBCL.¹

References

1. Abramson JS, Solomon SR, Arnason JE, et al. Lisocabtagene maraleucel versus standard of care with salvage chemotherapy followed by autologous stem cell transplantation as second-line treatment in patients with relapsed or refractory large B-cell lymphoma: primary analysis of the randomized, phase 3 TRANSFORM study. Presented at: 64th American Society of Hematology Annual Meeting and Exposition, December 10-13, 2022; New Orleans, LA. Oral presentation 655.
2. 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. Blood. December 2022; online ahead of print.