Indirect treatment comparison of brexucabtagene autoleucel (ZUMA-2) versus standard of care (SCHOLAR-2) in relapsed/refractory mantle cell lymphoma
Georg Heß, Martin Dreyling, Lucie Obéric, Eva Giné, Pier Luigi Zinzani, Kim Linton, Adam Vilmar, Mats Jerkeman, Jenny M. H. Chen, Anke Ohler, Stephan Stilgenbauer, Catherine Thiéblemont, Jonathan Lambert, Vittorio Ruggero Zilioli, Juan‐Manuel Sancho, Ana Jiménez Ubieto, Luca Fischer, Toby A. Eyre, Sam Keeping, Julie E. Park, James J. Wu, Ana Paiva Nunes, John A. Reitan, Sally W. Wade, Gilles Salles
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.