Number Needed to Treat to Avoid Progression or Death: Zanubrutinib vs Other Covalent Bruton Tyrosine Kinase Inhibitors in Relapsed/Refractory Chronic Lymphocytic Leukemia

Constantine S. Tam, MD, presents a modeled analysis estimating the number needed to treat (NNT) to prevent one progression or death when using zanubrutinib versus other covalent Bruton tyrosine kinase inhibitors (BTKis) in patients with high-risk relapsed/refractory chronic lymphocytic leukemia (R/R CLL). Using data from key randomized trials (ALPINE, ELEVATE-RR, and ASCEND) and a previously published network meta-analysis, the authors derived comparative progression-free survival (PFS) estimates for zanubrutinib, ibrutinib, and acalabrutinib in high-risk populations. A proportional hazards framework was applied to calculate 24-month PFS and model NNT outcomes. In the base-case analysis, zanubrutinib demonstrated an NNT of 5 versus ibrutinib and 6 versus acalabrutinib to avoid one progression or death over 24 months. Scenario analyses suggested that, in a cohort of 100 patients, approximately 17–20 progression or death events could be avoided with zanubrutinib. Sensitivity analyses using ALPINE-derived data supported the robustness of these findings, while acknowledging limitations inherent to cross-trial modeling assumptions.