Dr Gupta on Updated Efficacy Data With Liso-Cel in Second-Line Relapsed/Refractory LBCL

"The 3-year update from TRANSFORM that was recently published seems to suggest that [the efficacy of liso-cel] is superior compared with the standard of care, [with a median EFS] of 29.5 months [vs] just 2.4 months, [respectively]."

Supriya Gupta, MD, an assistant professor of Medicine, Hematology, Oncology and Transplantation at the University of Minnesota Medical School, recently discussed the implications of data from the phase 3 TRANSFORM study (NCT03575351) regarding the use of lisocabtagene maraleucel (liso-cel; Breyanzi) as a second-line therapy for large B-cell lymphoma (LBCL).

TRANSFORM enrolled 184 patients with primary refractory or early relapsed LBCL who were eligible for autologous stem cell transplantation (ASCT), Gupta began. Patients were randomly assigned 1:1 to receive either liso-cel or a standard of care (SOC) regimen. The SOC arm consisted of 3 cycles of platinum-based immunochemotherapy, followed by high-dose chemotherapy and ASCT for patients who responded to initial treatment.

Primary results from the study demonstrated significant improvements in event-free survival (EFS), complete response (CR) rate, and progression-free survival (PFS) for liso-cel when compared to the SOC, Gupta reported. At a 3-year follow-up, with a median follow-up time of 33.9 months, liso-cel's superior and more durable efficacy was confirmed, she added. The median EFS was 29.5 months (95% CI, 9.5- not reached [NR]) for liso-cel vs 2.4 months (95% CI, 2.2-4.9) with the SOC (HR, 0.375; 95% CI, 0.259-0.542).

Similarly, the median PFS was NR (12.6-NR) for liso-cel vs 6.2 months (4.3-8.6) for the SOC (HR, 0.422; 95% CI, 0.279-0.639), with 36-month PFS rates of 51% for liso-cel vs 26.5% for the SOC. The median overall survival (OS) was NR for both arms (HR, 0.757; 95% CI, 0.481-1.191). Notably, 66% of patients in the SOC arm crossed over to receive liso-cel. After accounting for the treatment effect of this crossover, the HR for OS was 0.566 (95% CI, 0.359-0.895) and favored liso-cel. The 36-month OS rates were 63% for liso-cel vs 52% for SOC.

The safety profile of liso-cel was consistent with prior reports, Gupta continued. The incidence of cytokine release syndrome (CRS) as approximately 50%;the majority were grade 1/2 and deemed manageable. Moreover, the incidence of neurotoxicity was lower with liso-cel vs SOC, indicating a very tolerable profile for liso-cel.

These comprehensive data collectively support liso-cel as an effective second-line treatment with curative potential for patients with relapsed/refractory LBCL when compared to the current SOC, Gupta concluded.