Toxicity, progression-free survival, and quality of life of patients treated with zanubrutinib versus ibrutinib: a Q-TWiST analysis from the ALPINE study in relapsed or refractory chronic lymphocytic leukemia.

Zanubrutinib demonstrated significantly longer progression-free survival versus ibrutinib in patients with relapsed/refractory chronic lymphocytic leukemia (R/R CLL) in the ALPINE trial. This post-hoc analysis using ALPINE data aimed to understand the benefit-risk associated with zanubrutinib versus ibrutinib employing quality-adjusted time without symptoms/toxicity (Q-TWiST) methodology. Survival data were partitioned into 3 health-states: TOX (time with toxicity); TWiST (time without symptoms/toxicity); and REL (time after relapse). Q-TWiST was estimated as mean time in each health-state weighted by respective utility score. In the base case, comprising high-risk patients, mean durations (in months) for zanubrutinib versus ibrutinib were 11.54 versus 11.38 (TOX), 14.45 versus 11.09 (TWiST), and 1.70 versus 3.78 (REL). Mean duration of Q-TWiST was 21.07 (zanubrutinib) versus 18.67 months (ibrutinib; difference: 2.40 months; 95%CI: 1.9-2.9; p<.001). This analysis demonstrated a significant Q-TWiST gain for zanubrutinib versus ibrutinib in high-risk R/R CLL patients, providing valuable insights that may inform clinical decision-making.