Comparative effectiveness of ZUMA-5 (axi-cel) vs SCHOLAR-5 external control in relapsed/refractory follicular lymphoma

Abstract

In the pivotal ZUMA-5 trial, axicabtagene ciloleucel (axi-cel; an autologous anti-CD19 chimeric antigen receptor T-cell therapy) demonstrated high rates of durable response in relapsed/refractory (r/r) follicular lymphoma (FL) patients. Here, clinical outcomes from ZUMA-5 are compared to the international SCHOLAR-5 external control cohort, which applied ZUMA-5 trial eligibility criteria to emulate RCT conditions. SCHOLAR-5 data were extracted from institutions in five countries for r/r FL patients who initiated a ≥3rd line of therapy after July 2014. Patient characteristics were balanced through propensity scoring on pre-specified prognostic factors using standardized mortality ratio (SMR) weighting. Time-to-event outcomes were evaluated using Kaplan-Meier analysis. Overall response rate (ORR) and complete response (CR) rate were compared using odds ratios. The 143 patients identified in SCHOLAR-5 reduced to an effective sample of 85 patients after SMR weighting, versus 86 patients in ZUMA-5. Median follow-up time was 25.4 and 23.3 months for SCHOLAR-5 and ZUMA-5. The median overall survival (OS) and progression-free survival (PFS) in SCHOLAR-5 were 59.8 months and 12.7 months, and were not reached in ZUMA-5. The hazard ratios for OS and PFS were 0.42 (95% confidence interval [CI]: 0.21-0.83) and 0.30 (95%CI: 0.18-0.49). The ORR and CR rate were 49.9% and 29.9% in SCHOLAR-5 compared to 94.2% and 79.1% in ZUMA-5, for odds ratios of 16.2 (95%CI: 5.6-46.9) and 8.9 (95%CI: 4.3-18.3). Compared to available therapies, axi-cel demonstrated an improvement in meaningful clinical endpoints. This study suggests axi-cel may address an important unmet need for r/r FL patients.