INTRODUCTION: Given its recent approval (5/15/19) in chronic lymphocytic leukemia (CLL)/small lymphocytic leukemia (SLL), little is known about real-world outcomes of 12-cycle fixed-duration venetoclax + obinutuzumab (V+G) treatment. This study evaluated time to discontinuation (TTD) and characteristics associated with TTD for first-line (1L) V+G. Methods: The nationwide Flatiron Health electronic health record-derived de-identified database (4/11/15-6/30/21) was used to select adults with CLL/SLL initiating 1L V (index date) between 4/11/16-7/31/20 to allow observation of ≥12 treatment cycles before the end of data. Patient characteristics were described during the 12-month pre-index period (baseline) and during the initiation (first 60 days)/post-initiation (day 61+) phases. TTD was defined as the time from index date to the earliest of the day before a treatment gap >120 days or the day before switching therapy. Results: Among 232 patients receiving 1L V-based regimens, 192 (82.8%) received V+G (others received V monotherapy [8.6%], V + rituximab [5.6%], and other V-based regimens [3.0%]), of which 113 (58.9%) initiated treatment on or before 7/31/20. Among these 113 patients, mean age was 65.9 years and 31.9% were female. During the initiation phase, 3.5% developed tumor lysis syndrome (TLS), and use of corticosteroids (100.0%) and antihyperuricemics (78.8%) was higher than in the post-initiation phase (67.0% and 45.5%). Mean (median) duration of active treatment was 11.6 (12.1) months; 16.8% discontinued treatment before completing 12 cycles, 68.1% completed ≥12 cycles, and 20.4% completed ≥15 cycles; 15.0% did not have enough follow-up to confirm completion of 12 cycles. Kaplan Meier analysis of TTD showed that most patients discontinued V+G around the 12-cycle mark (Fig. 1a). Patients discontinuing treatment in the first 12 cycles were older and had higher baseline risk of cardiovascular events and TLS (based on chronic kidney disease or creatine clearance <60 mL/min) relative to those who completed ≥12 cycles (Fig. 1b). Conclusion: Among patients initiating 1L CLL/SLL therapy with V, 82.8% received V+G, 16.8% of which discontinued before completing 12 cycles. Patients who discontinued were older and had higher disease burden and TLS risk. Treatment utilization was more intense during the initiation phase, potentially related to TLS mitigation and management. Unmet therapeutic needs remain among patients at higher disease burden or TLS risk.
Abbreviations: IL: first line; CCI: Charlson Comorbidity Index; CI: confidence interval; CLL: chronic lymphocytic leukemia; ECOG: Eastern Cooperative Oncology Group; SD: standard deviation; SLL: small lymphocytic lymphoma; TLS: tumor lysis syndromc; V-G: venetoclax + obinutuzumab.
Refers to the population at risk of having the event at that point in time (i.e., patients who have not had the event and have not been lost to follow-up).
The 12 cycles consist of 28 days each, to reflect a full course of fixed-duration treatment with venetoclax + obinutuzumab.