Matching-adjusted indirect treatment comparison of liso-cel versus axi-cel in relapsed or refractory large B cell lymphoma

Maloney, David G.; Kuruvilla, John; Liu, Fei Fei; Kostic, Ana; Kim, Yeonhee; Bonner, Ashley; Zhang, Yixie; Fox, Christopher P.; Cartron, Guillaume

Abstract

Background: In the absence of randomized studies directly comparing chimeric antigen receptor T cell therapies, this study used matching-adjusted indirect comparisons (MAIC) to evaluate the comparative efficacy and safety of lisocabtagene maraleucel (liso-cel) versus axicabtagene ciloleucel (axi-cel) in patients with relapsed or refractory large B cell lymphoma (LBCL). Methods: Primary data sources included individual patient data from the TRANSCEND NHL 001 study (TRANSCEND [NCT02631044]; N = 256 for efficacy set, N = 269 for safety set) for liso-cel and summary-level data from the ZUMA-1 study (NCT02348216; N = 101 for efficacy set, N = 108 for safety set) for axi-cel. Inter-study differences in design, eligibility criteria, baseline characteristics, and outcomes were assessed and aligned to the extent feasible. Clinically relevant prognostic factors were adjusted in a stepwise fashion by ranked order. Since bridging therapy was allowed in TRANSCEND but not ZUMA-1, the initial efficacy and safety analyses included bridging therapy use as a matching factor (TRANSCEND patients who received bridging therapy were removed). Subsequent sensitivity analyses excluded this matching factor. Results: The initial analysis showed similar MAIC-weighted efficacy outcomes between TRANSCEND and ZUMA-1 for overall and complete response rates (odds ratio [95% confidence interval (CI)], 1.40 [0.56–3.49] and 1.21 [0.56–2.64], respectively) and for overall survival and progression-free survival (hazard ratio [95% CI], 0.81 [0.44–1.49] and 0.95 [0.58–1.57], respectively). MAIC-weighted safety outcomes favored liso-cel, with significantly lower odds of all-grade and grade ≥ 3 cytokine release syndrome (odds ratio [95% CI], 0.03 [0.01–0.07] and 0.08 [0.01–0.67], respectively) and study-specific neurological events (0.16 [0.08–0.33] and 0.05 [0.02–0.15], respectively). Efficacy and safety outcomes remained similar in sensitivity analyses, which did not include use of bridging therapy as a matching factor. Conclusions: After matching and adjusting for clinically relevant prognostic factors, liso-cel demonstrated comparable efficacy and a more favorable safety profile compared with axi-cel in patients with third- or later-line relapsed or refractory LBCL. Trial registration: NCT02631044 and NCT02348216

Citation

Maloney, D. G., Kuruvilla, J., Liu, F. F., Kostic, A., Kim, Y., Bonner, A., …Cartron, G. (2021). Matching-adjusted indirect treatment comparison of liso-cel versus axi-cel in relapsed or refractory large B cell lymphoma. Journal of Hematology and Oncology, 14(1), Article 140. https://doi.org/10.1186/s13045-021-01144-9

• Journal Article Type: Article
• Acceptance Date: Aug 21, 2021
• Online Publication Date: Sep 8, 2021
• Publication Date: Sep 8, 2021
• Deposit Date: Feb 8, 2023
• Publicly Available Date: Feb 8, 2023
• Journal: Journal of Hematology & Oncology
• Print ISSN: 1756-8722
• Electronic ISSN: 1756-8722
• Publisher: BioMed Central
• Peer Reviewed: Peer Reviewed
• Volume: 14
• Issue: 1
• Article Number: 140
• DOI: https://doi.org/10.1186/s13045-021-01144-9
• Keywords: Cancer Research; Oncology; Molecular Biology; Hematology
• Public URL: https://nottingham-repository.worktribe.com/output/17078658
• Publisher URL: https://jhoonline.biomedcentral.com/articles/10.1186/s13045-021-01144-9