An unanchored matching-adjusted indirect comparison of the efficacy of zanubrutinib versus ibrutinib for the treatment of relapsed/refractory mantle-cell lymphoma

No head-to-head trials have compared the efficacy of zanubrutinib versus ibrutinib in relapsed/refractory mantle-cell lymphoma (R/R MCL). Following a systematic literature review, individual patient data from trials of zanubrutinib (n = 118) and aggregate data from a pooled analysis of ibrutinib trials (n = 370) were analyzed using an unanchored matching-adjusted indirect comparison (MAIC). After matching selected covariates, statistically significant differences were observed with zanubrutinib versus ibrutinib for progression-free survival (hazard ratio [HR] = 0.63; 95% confidence interval [CI] 0.46-0.87, p = .0044) and overall survival (HR, 0.46; 95% CI 0.30-0.71, p = .0005). These MAIC analyses demonstrate that zanubrutinib may be more effective than ibrutinib at delaying disease progression and death in R/R MCL. Mantle-cell lymphoma (MCL) is a rare and fast-growing form of non-Hodgkin lymphoma, a cancer that affects white blood cells (lymphocytes). Most patients with MCL experience either a return of their cancer (relapse) or their cancer stops responding (is refractory) to further treatments. Bruton tyrosine kinase inhibitors such as ibrutinib and zanubrutinib are standard-of-care medications used to treat relapsed or refractory MCL (R/R MCL). While medications are compared to others in clinical trials, no clinical trials have directly compared how well ibrutinib and zanubrutinib work versus each other in patients with R/R MCL. Although the most accurate way to compare treatments is by studying them in the same clinical trial, when these direct comparisons are not available, a method called matching-adjusted indirect comparison (MAIC) may help doctors decide which treatments to recommend. MAICs use results from different clinical trials and compare them to each other while adjusting for key differences in the study population. Our indirect comparison suggested better survival outcomes for patients with R/R MCL who were treated with zanubrutinib compared with ibrutinib. Zanubrutinib improved progression-free survival (which is the length of time where a patient’s cancer does not grow or return) and overall survival (the length of time that patients live for after starting treatment) compared with ibrutinib. Because the treatments were not tested in the same trial, these results are less certain than if results existed from a direct comparison. Our MAIC study shows that zanubrutinib may be more effective than ibrutinib for treating patients with R/R MCL.