Clinical Outcomes in Patients With CLL Treated With BTKi at a Large US Cancer Center

Patients with chronic lymphocytic leukemia (CLL) treated with covalent Bruton's tyrosine kinase inhibitors (BTKi) eventually discontinue treatment, but data on outcomes post-BTKi treatment discontinuation are limited. In this single-institution, retrospective chart review of 104 adult patients with CLL treated with a covalent BTKi between July 2011 and April 2019 and who subsequently discontinued for any reason, the majority of patients (59.9%) received the index BTKi in their first (27.5%) or second (32.4%) line of therapy. Median progression-free survival (PFS) from index BTKi initiation was 3.2 years, and median overall survival (OS) was 8.9 years. There was a notable correlation between PFS and OS (r = 0.79). Following the discontinuation of their last BTKi treatment, over half of these patients received subsequent therapies (80.6% of whom received regimens containing B-cell lymphoma 2 inhibitors [BCL2i]). Of the patients who received BCL2i-containing therapy after index BTKi treatment, 77.8% achieved an overall response to BCL2i at first clinical assessment. However, 73.8% of the patients exposed to BTKi and BCL2i eventually discontinued BCL2i treatment and 36.1% died, with a median follow-up of 2.6 years from BCL2i initiation. A subset of patients who were exposed to and were found to be relapsed, refractory, resistant, or intolerant to both BTKi and BCL2i-based regimens (n = 25) had high rates of progressive disease at first assessment (15.0%) and death (44.0%). These findings highlight an unmet clinical need for patients with CLL and underscore the urgency to develop effective new strategies to treat those patients who have already received covalent BTKi and BCL2i.