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

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.

Keywords: Axicabtagene ciloleucel; CAR T cell therapy; Indirect treatment comparison; Lisocabtagene maraleucel; Matching-adjusted indirect comparison.

Conflict of interest statement

DGM has received consultancy fees for scientific advisory board membership from A2 Biotherapeutics; honoraria from Amgen, BioLineRx, Bristol-Myers Squibb, Celgene, a Bristol-Myers Squibb Company, Genentech, Gilead Sciences, Janssen, Juno Therapeutics, a Bristol-Myers Squibb Company, Kite Pharma, a Gilead Company, Legend Biotech, MorphoSys, Novartis, and Pharmacyclics; and grants for research paid directly to his institution from Celgene, a Bristol-Myers Squibb Company, Juno Therapeutics, a Bristol-Myers Squibb Company, and Kite Pharma, a Gilead Company. He has patents with Juno Therapeutics, a Bristol-Myers Squibb Company (not licensed, no royalties), and stock options in A2 Biotherapeutics. JK has received consultancy fees from AbbVie, Bristol-Myers Squibb, Gilead Sciences, Karyopharm Therapeutics, Merck, Roche, and Seattle Genetics; honoraria from Amgen, Antengene, AstraZeneca, Celgene, a Bristol-Myers Squibb Company, Gilead Sciences, Janssen, Karyopharm Therapeutics, Merck, Novartis, Pfizer, Roche, Seattle Genetics, and TG Therapeutics; and grants for research from AstraZeneca, Janssen, and Roche. FFL, AK, and YK are employees of Bristol-Myers Squibb and hold stock in Bristol-Myers Squibb. AB and YZ are employees of EVERSANA, which received funding from Bristol-Myers Squibb to conduct the analyses. CPF has received honoraria from AbbVie, Adienne, AstraZeneca, Atara Biotherapeutics, Celgene, a Bristol-Myers Squibb Company, Genmab, Gilead Sciences, Incyte, Roche, Sunesis Pharmaceuticals, and Takeda; and grants for research from AbbVie, Adienne, Gilead Sciences, Roche, and Takeda. GC has received consultancy fees from Celgene, a Bristol-Myers Squibb Company, and F. Hoffmann-La Roche and honoraria from AbbVie, Celgene, a Bristol-Myers Squibb Company, F. Hoffmann-La Roche, Gilead Sciences, Janssen, and Sanofi.

© 2021. The Author(s).

Figures

Fig. 1

Kaplan–Meier curves for progression-free survival. Kaplan–Meier curves are shown for the initial and sensitivity analysis comparisons with liso-cel versus axi-cel for infused patients. Kaplan–Meier curves for the initial analysis, which matched and adjusted for 10 factors, including bridging therapy use, demonstrated similar cumulative probabilities of progression-free survival for liso-cel and axi-cel. Similar results were observed for sensitivity analysis 1, which was the same as the initial analysis except that bridging therapy use was removed as a matching factor. Axi-cel, axicabtagene ciloleucel; CI, confidence interval; ESS, effective sample size; liso-cel, lisocabtagene maraleucel; N, sample size; NR, not reached

Fig. 2

Kaplan–Meier curves for overall survival. Kaplan–Meier curves are shown for the initial and sensitivity analysis comparisons with liso-cel versus axi-cel for infused patients. Kaplan–Meier curves for the initial analysis, which matched and adjusted for 10 factors, including bridging therapy use, demonstrated similar cumulative probabilities of OS for liso-cel and axi-cel. Similar results were observed for sensitivity analysis 1, which was the same as the initial analysis except that bridging therapy use was removed as a matching factor. Axi-cel, axicabtagene ciloleucel; CI, confidence interval; ESS, effective sample size; liso-cel, lisocabtagene maraleucel; N, sample size; NR, not reached