Matching-adjusted indirect comparison of zanubrutinib and real-world chemotherapy, rituximab and chemoimmunotherapy in relapsed or refractory marginal zone lymphoma

Aim: Traditional management of relapsed or refractory (R/R) marginal zone lymphoma (MZL) comprises chemotherapy, rituximab or rituximab-based chemoimmunotherapy (CIT). Zanubrutinib, a Bruton tyrosine kinase inhibitor, has shown high overall response rates and durable responses across MZL subtypes in two Phase II, single-arm trials. As no head-to-head randomized study exists, an unanchored matching-adjusted indirect comparison was performed to estimate the relative efficacy of zanubrutinib versus traditional agents. Materials & methods: Pooled patient-level data for 86 evaluable patients from zanubrutinib trials were compared with aggregate-level data from 90 patients treated with chemotherapy, rituximab or CIT in the Haematological Malignancy Research Network registry. Logistic propensity score models were used to match the populations for key characteristics. Progression-free survival (PFS) and overall survival (OS) associated with each treatment were estimated from Cox models. Since patients receiving chemotherapy generally have less favorable outcomes, a sensitivity analysis comparing zanubrutinib against CIT or rituximab alone was performed. Leave-one-out analyses were conducted where one covariate at a time was omitted to explore its impact on the results. Results: The effective sample size for zanubrutinib after matching was 38. Compared with chemotherapy, rituximab or CIT, zanubrutinib significantly increased PFS (hazard ratio [HR]: 0.30 [95% CI: 0.15–0.63]; p = 0.001) and OS (HR: 0.23 [95% CI: 0.10–0.50]; p < 0.001) in patients with R/R MZL. Findings were consistent across leave-one-out analyses and when excluding patients who received chemotherapy only. Conclusion: Modeling using clinical trial and real-world data from an unanchored matching-adjusted indirect comparison suggests that zanubrutinib was associated with longer PFS and OS compared with chemotherapy, rituximab or CIT in patients with R/R MZL.