Indirect Comparison of Liso-cel and Axi-cel for 2L Treatment of R/R LBCL Revealed Comparable Efficacy with Safety Outcomes Favoring Liso-cel

Two chimeric antigen receptor T-cell (CAR-T) therapies, lisocabtagene maraleucel (liso-cel) and axicabtagene ciloleucel (axi-cel), demonstrated superior efficacy over salvage chemotherapy and autologous stem-cell transplant (ASCT)—for chemotherapy-sensitive disease—as second-line (2L) therapy in transplant-intended patients with high-risk relapsed or refractory (R/R) large B-cell lymphoma (LBCL). However, no head-to-head clinical trials have compared the 2 CAR-T therapies. Data from a matching-adjusted indirect comparison (MAIC) of treatment effects in the 2L setting for liso-cel versus axi-cel in patients with R/R LBCL were reported at the 64th American Society of Hematology Annual Meeting and Exposition.

MAICs were used to estimate population-adjusted relative treatment effects associated with liso-cel (TRANSFORM [NCT03575351], N = 184) versus axi-cel (ZUMA-7 [NCT03391466], N = 359) for event-free survival (EFS), progression-free survival (PFS), objective response rate (ORR), and complete response (CR) rate, in addition to safety (TRANSFORM, N = 183; ZUMA-7, N = 338). For optimal adjustment and matching, patients from TRANSFORM were excluded if they did not satisfy eligibility criteria specified in ZUMA-7, whereas individual patient data (IPD) for patients who remained in the TRANSFORM data set were weighted regarding the distribution of clinical factors in ZUMA-7. Efficacy comparisons were made through the common comparator standard of care. Hazard ratios were used to compare time to event outcomes (EFS and PFS), and odds ratios (ORs) were used for comparisons between binary outcomes (ORR, CR rate, and safety). Selection and rank ordering of the treatment effect modifiers were guided by analysis of the TRANSFORM IPD as well as a panel of expert clinicians. Factors to match and adjust for efficacy included (in rank order) central nervous system involvement, absolute lymphocyte count, age, sex, geographic region, secondary age-adjusted International Prognostic Index (sAAIPI) score, sum of the product of perpendicular diameters of lesions at baseline, R/R status to first-line therapy, double/triple-hit status, and disease histology. Factors for the safety MAIC included (in rank order) age, sAAIPI score, LVEF at screening, and bilirubin at screening. Bridging therapy was allowed in TRANSFORM but not in ZUMA-7, which was not practical to adjust for given sample size constraints.

Matching with ZUMA-7 for patient eligibility and adjusting for the selected effect modifiers resulted in effective sample sizes of 79 and 68 for the TRANSFORM efficacy and safety comparisons, respectively. MAIC efficacy results for these populations showed comparable efficacy of liso-cel and axi-cel for EFS, PFS, OS, and response. MAIC safety results demonstrated lower odds of key CAR-T‒associated adverse events with liso-cel versus axi-cel: any-grade cytokine release syndrome, or CRS (OR, 0.09; 95% confidence interval [CI], 0.04 0.18); grade ≥3 CRS (OR, 0.09; 95% CI, 0.01-0.75); any-grade neurological events, or NEs (OR, 0.08; 95% CI, 0.03-0.18); and grade ≥3 NEs (OR, 0.21; 95% CI, 0.06-0.68).

Findings from this comparative analysis of liso-cel and axi-cel for the 2L treatment of R/R LBCL show similar efficacy of liso-cel and axi-cel, with lower odds of all-grade and grade ≥3 CRS and NEs observed with liso-cel. These results indicate liso-cel may have a preferable safety profile over axi-cel in the treatment of transplant-eligible patients with LBCL in the 2L setting and beyond.

Source

Abramson JS, Kamdar M, Liu FF, et al. Matching-adjusted indirect comparison of lisocabtagene maraleucel versus axicabtagene ciloleucel for second-line treatment of patients with refractory/early relapsed large B-cell lymphoma. Presented at: 64th American Society of Hematology Annual Meeting and Exposition, December 10-13, 2022; New Orleans, LA. Poster presentation 2031.