Brexu-cel Has ‘Substantial’ Benefit Over SOC in Relapsed or Refractory MCL Post-BTKi Therapy

Researchers demonstrated a “substantial treatment benefit” in an indirect treatment comparison of brexucabtagene autoleucel (brexu-cel) with the standard of care in patients with relapsed or refractory mantle cell lymphoma (MCL) after Bruton tyrosine kinase inhibitor (BTKi) exposure, according to a study published in Leukemia and Lymphoma.

The study, led by Georg Hess, MD, of the University Medical School of the Johannes Gutenberg-University, compared overall survival (OS) in two previous studies, ZUMA-2 and SCHOLAR-2.

OS was compared using three methods, which adjusted for imbalances in prognostic factors between populations: inverse probability weighting (IPW), regression adjustment (RA), and doubly robust (DR). Researchers found that brexu-cel in the ZUMA-2 study was associated with improved OS compared with the standard of care (SOC) in the SCHOLAR-2 study across all unadjusted and adjusted comparisons. The most common SOC regimens included bendamustine plus rituximab and lenalidomide plus rituximab.

ZUMA-2 was a single-arm, phase II trial that included 68 patients with relapsed or refractory MCL who had previous BTKi exposure. Meanwhile, SCHOLAR-2 was a retrospective, observational, chart review study that collected survival outcomes of 149 patients with MCL who experienced disease progression while on BTKi therapy or were intolerant to BTKi therapy.

“These results suggest a substantial survival benefit with brexu-cel versus SOC in patients with [relapsed or refractory] MCL after BTKi exposure,” wrote Hess and colleagues.

Researchers also identified four variables as key prognostic factors to be balanced between populations: response to prior BTKi therapy, duration on prior BTKi therapy, number of prior lines of therapy, and whether they had prior autologous stem cell transplantation.

Both duration on prior BTKi therapy and response to prior BTKi therapy had an absolute standardized difference (ASD) of <10% between ZUMA-2 and SCHOLAR-2 populations, indicating good balance between both groups. However, the proportion of patients with prior autologous stem cell transplantation (SCT) was slightly higher in ZUMA-2 than SCHOLAR-2 (43% vs 37%, respectively), and the proportion of patients with ≥3 prior lines of therapy was also higher in ZUMA-2 (81% vs 60%, respectively).

The researchers noted that because of the small sample size, “results should be interpreted with caution; nevertheless, our findings suggest that brexu-cel can help address the significant lack of effective treatments for patients with [relapsed or refractory] MCL who have previously received a covalent BTKi therapy.”

Reference:

Hess G, Dreyling M, Oberic L, et al. Indirect treatment comparison of brexucabtagene autoleucel (ZUMA-2) versus standard of care (SCHOLAR-2) in relapsed/refractory mantle cell lymphoma. Leukemia and Lymphoma. 2023. doi.org/10.1080/10428194.2023.2268228