Indirect treatment comparison of brexucabtagene autoleucel (ZUMA-2) versus standard of care (SCHOLAR-2) in relapsed/refractory mantle cell lymphoma

Abstract

The SCHOLAR-2 retrospective study highlighted poor overall survival (OS) with standard of care (SOC) regimens among patients with relapsed/refractory (R/R) mantle cell lymphoma (MCL) who failed a covalent Bruton tyrosine kinase inhibitor (BTKi). In the ZUMA-2 single-arm trial, brexucabtagene autoleucel (brexu-cel; autologous anti-CD19 CAR T-cell therapy) demonstrated high rates of durable responses in patients with R/R MCL who had previous BTKi exposure. Here, we compared OS in ZUMA-2 and SCHOLAR-2 using three different methods which adjusted for imbalances in prognostic factors between populations: inverse probability weighting (IPW), regression adjustment (RA), and doubly robust (DR). Brexu-cel was associated with improved OS compared to SOC across all unadjusted and adjusted comparisons. Hazard ratios (95% confidence intervals) were 0.38 (0.23, 0.61) for IPW, 0.45 (0.28, 0.74) for RA, and 0.37 (0.23, 0.59) for DR. These results suggest a substantial survival benefit with brexu-cel versus SOC in patients with R/R MCL after BTKi exposure.

Keywords:

• CAR T-cell therapy
• brexucabtagene autoleucel
• indirect treatment comparison
• mantle cell lymphoma
• non-Hodgkin lymphoma
• standard of care

Acknowledgement

G.H., G.S., M.D., L.O., E.G., P.L.Z., K.L., A.V., M.J., A.O., S.S., C.T., J.L., V.R.Z., J.M.S., A.J.U., L.F., and T.A.E. contributed to the study concept and design, data collection, and interpretation of data. J.M.H.C., J.E.P., and S.K. contributed to the study concept and design, analysis and interpretation of data, manuscript drafting, project administration, statistical analysis, and verification of the underlying data reported in the manuscript. J.J.W., S.W.W., and A.N. contributed to the study concept and design, interpretation of data, project administration, and verification of the underlying data reported in the manuscript. J.R. contributed to the study concept and design, and interpretation of data. All authors reviewed, revised, and approved the final manuscript for submission.

Disclosure statement

G.H. has received grants or contracts from Kite, a Gilead Company, Incyte, Janssen, Morphosys, Pfizer, Roche, and Abbvie; has received consulting fees from Abbvie, ADC-Therapeutics, AstraZeneca, BMS, Genmab, Kite, a Gilead Company, Incyte, Janssen, Miltenyi, Novartis, Roche, and Lilly; has received payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing or educational events from Abbvie, AstraZeneca, Beigene, BMS, Genmab, Kite, a Gilead Company, Incyte, Janssen, Lilly, and Roche; has received support for attending meetings and/or travel from Kite, a Gilead Company, and Janssen; and has participated on a Data Safety Monitoring Board or Advisory Board for Miltenyi. M.D. has received institutional support for clinical trials from Abbvie, Bayer, Celgene/BMS, Kite, a Gilead Company, Janssen, and Roche; has received payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing or educational events from Astra Zeneca, Beigene, Kite, a Gilead Company, Janssen, Lilly, Novartis, and Roche; has received support for attending meetings and/or travel from Janssen and Roche; and has participated on a Data Safety Monitoring Board or Advisory Board for Abbvie, AstraZeneca, Beigene, Celgene/BMS, Kite, a Gilead Company; Janssen, Lilly/Loxo, Novartis, Roche. L.O. has received payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing or educational events from Janssen; has received support for attending meetings and/or travel from Roche and AstraZeneca; and has participated on a Data Safety Monitoring Board or Advisory Board for Roche and Gilead Sciences. P.L.Z. has received consulting fees from MSD, Eusapharma, and Novartis; has received payment or honoraria for speakers bureaus from Celltrion, Gilead, Janssen-Cilag, BMS, Servier, MSD, AstraZeneca, Takeda, Roche, Eusapharma, Kyowa Kirin, Novartis, Incyte, Beigene; and has participated on an Advisory Board for Secura Bio, Celltrion, Gilead, Janssen-Cilag, BMS, Servier, Sandoz, MSD, AstraZeneca, Takeda, Roche, Eusapharma, Kyowa Kirin, Novartis, ADC Therapeutics, Incyte, and Beigene. K.L. has received consulting fees from Genmab, Roche, Kite, a Gilead Company, and Beigene; has received payment or honoraria for educational events from Abbvie and Celgene/BMS; has received support for attending meetings from BMS and Takeda; and has leadership or fiduciary role in NCRI, EHA LyG, WiL, and Epcoritamab Global Council. A.V. has received payment or honoraria for educational events and support for attending meetings and/or travel from AstraZeneca; and has participation on a Data Safety Monitoring Board or Advisory Board for AstraZeneca. M.J. has received honoraria for lectures, presentations, speakers bureaus, manuscript writing or educational events from Abbvie, Pierre Fabre, and Kite, a Gilead Company. S.S. has received grants or contracts; consulting fees; payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing or educational events; support for attending meetings and/or travel; equipment, materials, drugs, medical, writing, gifts or other services; and payments for participation on a Data Safety Monitoring Board or Advisory Board from AbbVie, Acerta, Amgen, AstraZeneca, BeiGene, BMS, Celgene, Genentech, Gilead Sciences, GSK, Hoffmann-La Roche, Incyte, Infinity, Janssen, Novartis, Pharmacyclics, Sunesis, and Verastem. J.L. has received support for attending meetings and/or travel from Novartis, Takeda, BMS, and Kite, a Gilead Company; and participated on a Data Safety Monitoring Board or Advisory Board for Blueprint pharma and Kite, a Gilead Company. V.R.Z. has received payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing or educational events from Gentili, Incyte, Janssen, Lilly, Novartis, and Takeda; has received support for attending meetings and/or travel from Takeda, Janssen, and Roche; and has participated on a Data Safety Monitoring Board or Advisory Board for Kite, a Gilead Company, Janssen, MSD, Roche, Servier, and Takeda. J.M.S. has received honoraria for medical educational events from Roche, Kite, a Gilead Company, Celgene/BMS, Novartis, Janssen, and Incyte; has received honoraria for consultancy from Roche and Incyte; has received support for attending meetings and/or travel from Roche and Kite, a Gilead Company; and has received honoraria for participation in Advisory Board from Roche, Kite, a Gilead Company, Celgene/BMS, Novartis, Janssen, Incyte, Beigene, and Lilly. T.A.E. has received research funding from Beigene and AstraZeneca; has received consulting fees from Loxo Oncology, Janssen, Lilly, Abbvie, AstraZeneca, Roche, Incyte, Autolus, Beigene, and Kite, a Gilead Company; has received payments or honoraria for lectures, presentations, speakers bureaus, manuscript writing or educational events from Loxo Oncology, Janssen, Lilly, Abbvie, AstraZeneca, Roche, Beigene, and Kite, a Gilead Company. J.J.W. is an employee of Kite, a Gilead Company; has received honoraria from the Patient-Centered Outcomes Research Institute (PCORI), both as a member of the Rare Disease Advisory Panel, and as a grants reviewer for the Improving Methods Program; has received travel/meeting support from Kite, a Gilead Company, and Amgen; owns stock in Gilead Sciences, Amgen, Abbott, AbbVie, Pfizer, Roche, Curis, Avid Biosciences, Evofem, Lensar, VBI Vaccines, and Viracta Therapeutics. A.N. is an employee of Gilead Sciences Europe; own stocks in Gilead Sciences and Amgen; and has received support for attending meetings and/or travel from Kite, a Gilead Company; J.R. has received support from Kite, a Gilead Company and Janssen; S.W.W. has received consulting fees from Kite, a Gilead Company, Abbvie and Johnson & Johnson. G.S. has received consulting fees from Abbvie, Celgene/BMS, Epizyme, Genmab, Incyte, Janssen, Kite, a Gilead Company, Loxo, Milteniy, Molecular Partners, Morphosys, Nordic Nanovector, Novartis, Rapt, and Takeda; has received payment or honoraria for speaking in symposium from Bayer, Epizyme, and Regeneron; has participated on a Data Safety Monitoring board or Advisory Board for Beigene; and has stock or stock options from Owkin. J.M.H.C., S.K., and J.E.P. are employees of PRECISIONheor which received funding for this study from Kite, a Gilead Company. E.G., A.O., C.T., A.J.U., and L.F. declare no competing interests.

Additional information

Funding

This study was sponsored by Kite, a Gilead Company.