Real-World Treatment Patterns After Discontinuation of Venetoclax or BTKis in the Frontline Setting Among Older Adults With Chronic Lymphocytic Leukemia

PURPOSE Venetoclax and Bruton’s tyrosine kinase inhibitors (BTKis) are key treatment options for patients with chronic lymphocytic leukemia (CLL) in the frontline setting. This study characterized postdiscontinuation treatment patterns and hospitalization of frontline venetoclax and BTKis in a national sample of older adults with CLL. METHODS We identified 1,770 Medicare beneficiaries 66 years and older with CLL initiating venetoclax with obinutuzumab (VEN-O, n 5 193) or BTKi treatment (n 5 1,577) in the frontline setting between June 01, 2019, and June 30, 2020. Discontinuation was defined as a consecutive 90-day gap in treatment at any point over an 18-month follow-up. BTKi patients were expected to receive treatment continuously; VEN-O patients were expected to complete 11 months of treatment (12 cycles 3 28 days 5 336 days). The rates of subsequent CLL treatment and all-cause/CLL-related hospitalization were assessed. RESULTS Over an 18-month follow-up, 102 (52.8%) VEN-O patients discontinued after completing the fixed-duration period; 597 (37.9%) BTKi and 57 (29.5%) VEN-O patients discontinued treatment prematurely. The median time to discontinuation was 11.9 months (VEN-O) and 4.0 months (BTKi patients), respectively. Few patients (n < 11) who discontinued VEN-O initiated another CLL treatment over a median postdiscontinuation follow-up period of 6.1 months. By contrast, 39.0% of discontinuers in the BTKi group had evidence of subsequent CLL treatment over a median 13.8-month postdiscontinuation follow-up period. Post-BTKi regimens included BCL-2 (35.6%), subsequent BTKi (31.8%), chemotherapy (14.6%), anti-CD20 monotherapy (9.9%), and other (8.2%). The rate of postdiscontinuation all-cause and CLL-related hospitalization per 100 patient-months was 2.0 and 1.5 for the VEN-O group and 3.3 and 2.9 for the BTKi group, respectively. CONCLUSION In this real-world study, early discontinuation was more common in patients initiating a BTKi in contrast to VEN-O. Patients who initiated a BTKi also had high rates of subsequent treatment and hospitalization.