Venetoclax-rituximab is active in patients with BTKi-exposed CLL, but durable treatment-free remissions are uncommon

Targeted agent-based therapies such as covalent Bruton tyrosine kinase inhibitors (cBTKis) and venetoclax (VEN) plus anti-CD20 monoclonal antibodies have achieved superior outcomes over chemoimmunotherapy among patients with CLL with a range of fitness and comorbidity levels, in the first-line and relapsed/refractory (RR) settings. [1][2]2][3][4][5][6][7] However, data to inform the optimal sequencing of targeted agents remain limited. [8][9]][10] Continuous VEN monotherapy has demonstrated efficacy in a prospective trial with patients who were heavily pretreated with either cBTKi failure or intolerance. 8However, patients with prior B-cell receptor signaling inhibitor exposure were minimally represented (n = 5) in the phase 3 MURANO study of time-limited VEN-rituximab (VEN-R).Consequently, the outcomes with time-limited VEN-R in this context are unknown. 4Given the poor survival of patients with 11,12 time-limited therapy is attractive to mitigate the emergence of resistance, potentially enabling retreatment.[13][14][15][16][17] To address this data gap, we report outcomes of an Australian multicenter real-world cohort of patients receiving time-limited VEN-R for cBTKi-exposed CLL.