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, outcomes from ZUMA-5 are compared with the international SCHOLAR-5 cohort, which applied key ZUMA-5 trial eligibility criteria simulating randomized controlled trial conditions. SCHOLAR-5 data were extracted from institutions in 5 countries, and from 1 historical clinical trial, for r/r FL patients who initiated a third or higher line of therapy after July 2014. Patient characteristics were balanced through propensity scoring on prespecified prognostic factors using standardized mortality ratio (SMR) weighting. Time-to-event outcomes were evaluated using weighted Kaplan-Meier analysis. Overall response rate (ORR) and complete response (CR) rate were compared using weighted odds ratios. The 143 ScHOLAR-5 patients reduced to an effective sample of 85 patients after SMR weighting vs 86 patients in ZUMA-5. Median follow-up time was 25.4 and 23.3 months for SCHOLAR-5 and ZUMA-5. Median overall survival (OS) and progression-free survival (PFS) in SCHOLAR-5 were 59.8 months and 12.7 months and not reached in ZUMA-5. 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 and 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 with available therapies, axi-cel demonstrated an improvement in meaningful clinical endpoints, suggesting axi-cel addresses an important unmet need for r/r FL patients. This trial was registered at www.clinicaltrials.gov as #NCT03105336.

• Authors: Paola Ghione, M Lia Palomba, Anik R Patel, Sabela Bobillo, Kevin Deighton, Caron A Jacobson, Myrna Nahas, Anthony J Hatswell, A Scott Jung, Steve Kanters, Julia Thornton Snider, Sattva S Neelapu, Maria Teresa Ribeiro, M Alan Brookhart, Herve Ghesquieres, John Radford, John G Gribben
• Journal: Blood (Blood) Vol. 140 Issue 8 Pg. 851-860 (08 25 2022) ISSN: 1528-0020 [Electronic] United States
• PMID: 35679476 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: © 2022 by The American Society of Hematology.

Chemical References

• Antigens, CD19

Topics

• Antigens, CD19 (therapeutic use)
• Cohort Studies
• Humans
• Immunotherapy, Adoptive (adverse effects)
• Lymphoma, Follicular (drug therapy)
• Lymphoma, Large B-Cell, Diffuse (pathology)