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

• Published in: Journal of hematology and oncology Vol. 14; no. 1; pp. 1 - 17
• Main Authors: Maloney, David G., Kuruvilla, John, Liu, Fei Fei, Kostic, Ana, Kim, Yeonhee, Bonner, Ashley, Zhang, Yixie, Fox, Christopher P., Cartron, Guillaume
• Format: Journal Article
• Language: English
• Published: London BioMed Central 08.09.2021; BioMed Central Ltd; BMC
• Subjects: Adult; Aged; Anemia; Antineoplastic Agents, Immunological; Aphasia; Axicabtagene ciloleucel; B-cell lymphoma; Biological Products; Cancer; Cancer Research; CAR T cell therapy; Chemotherapy; Chimeric antigen receptors; Comparative analysis; Cytokines; Enrollments; Female; Hematology; Histology; Human health and pathology; Humans; Immunology; Immunotherapy; Immunotherapy, Adoptive; Indirect treatment comparison; Life Sciences; Lisocabtagene maraleucel; Lymphocytes; Lymphocytes T; Lymphoma; Lymphoma, Large B-Cell, Diffuse; Male; Matching-adjusted indirect comparison; Medicine; Medicine & Public Health; Middle Aged; Neoplasm Recurrence, Local; Neutropenia; Non-Hodgkin's lymphomas; Oncology; Patients; Response rates; Safety; Sensitivity analysis; T cells; Thrombocytopenia; Treatment Outcome; Matching-adjusted indirect comparison; CAR T cell therapy; Lisocabtagene maraleucel; Indirect treatment comparison; Axicabtagene ciloleucel
• ISSN: 1756-8722; 1756-8722
• DOI: 10.1186/s13045-021-01144-9

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