Time to Discontinuation of First-Line Venetoclax Plus Obinutuzumab Among Patients With CLL or SLL

Patients with chronic lymphocytic leukemia (CLL) or small lymphocytic lymphoma (SLL) who discontinued venetoclax as first-line therapy were older and had a greater disease burden and risk of tumor lysis syndrome (TLS) when compared with those patients who completed at least 12 cycles of treatment, according to results of an analysis of real-world data from the nationwide Flatiron Health electronic health record-derived database (JCCN. 2022; 20(3.5);10.6004/jnccn.2021.7275 doi:10.6004/ jnccn.2021.7275).

Because treatment with 12 cycles of venetoclax plus obinutuzumab for a fixed duration in patients with CLL or SLL was only recently approved in mid-May of 2019, little was known about treatment outcomes in these patients. Therefore, to determine time to treatment discontinuation and patient characteristics associated with it, a North American team of researchers chose from the Flatiron Health database adults with CLL/SLL in whom first-line treatment with venetoclax was initiated between April 11, 2016, and July 31, 2020. This date range was selected to allow the researchers to observe at least 12 treatment cycles before data collection ended.

The researchers defined time to discontinuation (TTD) as the time from the index date of treatment initiation to the day before a treatment gap of more than 120 days, or the day before treatment was switched, whichever was earliest. They described patient characteristics during the year before the index date (baseline phase), during the first 60 days after treatment initiation (initiation phase), and during the treatment period thereafter (post-initiation phase).

Of the 232 patients selected from the database, 192 (83%) were found to have received venetoclax plus obinutuzumab, which was initiated on or before July 31, 2020 in 113 patients (59%). In this subgroup of 113 patients, 32% were women, and the mean age was 66 years. 

During the treatment initiation phase, TLS developed in nearly 4% of this subgroup, and treatment with corticosteroids or antihyperuricemics was higher than it was in the post-initiation phase (100% vs. 67% for corticosteroids and 79% vs. 46% for antihyperuricemics, respectively, by phase). “Treatment utilization was more intense during the initiation phase, potentially related to TLS mitigation and management,” wrote Kerry Rogers, MD, Ohio State University, Columbus, OH, and colleagues.

The team also found that the mean duration of active treatment was 12 months and that 17% of the subgroup discontinued treatment before completing 12 cycles. Moreover, 68% completed more than 12 cycles, and 20% completed more than 15 cycles. However, 15% did not receive sufficient follow-up to confirm that they completed 12 cycles. Results of Kaplan Meier analysis revealed that most patient discontinued treatment after approximately 12 cycles.

“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 creatinine clearance <60 mL/min) relative to those who completed ≥12 cycles,” wrote Dr Rogers and colleagues. “Unmet therapeutic needs remain among patients at higher disease burden or TLS risk,” they concluded.