Zanubrutinib versus acalabrutinib indirect treatment comparison in relapsed or refractory mantle cell lymphoma

Leuk Lymphoma. 2025 Dec;66(12):2238-2248. doi: 10.1080/10428194.2025.2541911. Epub 2025 Sep 1.

Abstract

Zanubrutinib and acalabrutinib have demonstrated efficacy in separate single-arm clinical trials in patients with relapsed/refractory (R/R) mantle cell lymphoma (MCL). Given these single-arm trials lacked a common comparator, an unanchored indirect treatment comparison was conducted to assess the comparative efficacy of zanubrutinib versus acalabrutinib using a simulated treatment comparison (STC) method. In the base case analysis (adjusted for all covariates), zanubrutinib treatment was associated with significantly improved progression-free survival (hazard ratio [HR], 0.57 [95% confidence interval [CI], 0.35-0.94]; p = 0.0272) and overall survival (HR, 0.43 [95% CI, 0.23-0.82]; p = 0.0105) versus acalabrutinib. Overall response rate was numerically higher with zanubrutinib versus acalabrutinib (odds ratio [OR], 2.05 [95% CI, 0.72-5.84]; p = 0.1798). Sensitivity analyses, including a subset of covariates, provided consistent results. In the absence of a head-to-head trial, these results provide important insights into the comparative efficacy of zanubrutinib and acalabrutinib for physicians managing patients with R/R MCL.

Keywords: MCL; Zanubrutinib; acalabrutinib; indirect treatment comparison.

Publication types

  • Comparative Study

MeSH terms

  • Aged
  • Aged, 80 and over
  • Benzamides* / administration & dosage
  • Benzamides* / adverse effects
  • Benzamides* / therapeutic use
  • Drug Resistance, Neoplasm
  • Female
  • Humans
  • Lymphoma, Mantle-Cell* / drug therapy
  • Lymphoma, Mantle-Cell* / mortality
  • Lymphoma, Mantle-Cell* / pathology
  • Male
  • Middle Aged
  • Neoplasm Recurrence, Local* / drug therapy
  • Neoplasm Recurrence, Local* / pathology
  • Piperidines* / therapeutic use
  • Pyrazines* / administration & dosage
  • Pyrazines* / adverse effects
  • Pyrazines* / therapeutic use
  • Pyrazoles* / therapeutic use
  • Pyrimidines* / therapeutic use
  • Treatment Outcome

Substances

  • Pyrazines
  • acalabrutinib
  • zanubrutinib
  • Benzamides
  • Pyrazoles
  • Piperidines
  • Pyrimidines