The objective of this analysis was to evaluate outcomes of subsequent therapies following disease progression in patients with treatment‑naïve chronic lymphocytic leukemia or small lymphocytic lymphoma without del(17p) who were treated with zanubrutinib or bendamustine plus rituximab in cohort 1 of the Phase 3 SEQUOIA trial.

Cohort 1 of the Phase 3 SEQUOIA trial was a randomized study in which patients without del(17p) were assigned to receive continuous zanubrutinib or six cycles of bendamustine plus rituximab, with crossover to zanubrutinib permitted after disease progression. Patients were followed after progression for details of subsequent anti–chronic lymphocytic leukemia treatments. Endpoints assessed in this analysis included progression‑free survival, time to next treatment, time to next treatment or death, and progression‑free survival on subsequent therapy. P‑values were reported as descriptive.

A total of 479 patients were randomized (zanubrutinib, n=241; bendamustine plus rituximab, n=238). At a median follow‑up of 78.7 months, sustained progression‑free survival superiority was reported for zanubrutinib versus bendamustine plus rituximab (hazard ratio 0.28; 95% CI, 0.21–0.38; P<0.0001). Time to next treatment and time to next treatment or death favored zanubrutinib. Disease progression followed by subsequent therapy occurred in 10.0% of zanubrutinib‑treated patients and 34.0% of bendamustine plus rituximab–treated patients. Progression‑free survival on subsequent therapy favored zanubrutinib (hazard ratio 0.66; P<0.05), with 78‑month estimates of 81.3% versus 73.8%, respectively.