Matching-adjusted indirect comparisons of zanubrutinib (MAGNOLIA, BGB-3111-AU-003) versus ibrutinib (PCYC-1121) and rituximab (CHRONOS-3) in relapsed/refractory marginal zone lymphoma

In the absence of head-to-head randomized trials, unanchored matching-adjusted indirect comparisons were conducted to estimate the relative efficacy of zanubrutinib versus ibrutinib and zanubrutinib versus rituximab in relapsed or refractory marginal zone lymphoma (MZL). Logistic propensity score models were used to estimate weights for the patient-level data from two phase II single-arm trials, MAGNOLIA and BGB-3111-AU-003, such that their characteristics matched the ibrutinib and rituximab aggregate-level data from PCYC-1121 and CHRONOS-3, respectively. The base case model for each comparison incorporated four key prognostic factors: prior lines of therapy, MZL subtype, response to prior therapy, and age. A sensitivity analysis incorporating additional prognostic factors was also conducted for the ibrutinib comparison. The impact of each covariate was explored via a leave-one-out analysis. Compared with ibrutinib and rituximab, zanubrutinib demonstrated significant benefits in terms of both overall response and progression-free survival in patients with previously treated MZL.