Treatment Discontinuation Patterns Highlight Need for Tolerable CLL Therapies

Premature treatment discontinuations in the first and second lines of therapy among patients with chronic lymphocytic leukemia (CLL) occurred across all types of therapies and were mostly due to adverse events, according to results from an observational study published in Clinical Lymphoma, Myeloma & Leukemia. 

“Taken together, these findings suggest that there is an unmet clinical need for more tolerable therapies in CLL,” wrote corresponding author Beenish S. Manzoor, PhD, MPH, of AbbVie Inc, North Chicago, Illinois, and coauthors. “Novel agents, based on finite therapy durations, may potentially offer a better tolerated option for newly diagnosed or relapsed/refractory patients or reduce a time period over which the patient is exposed to the risk of adverse events.”

The real-world study included patients initiating first-line and second-line therapy from the CLL Collaborative Study of Real-World Evidence. Researchers assessed premature discontinuation rates across treatment cohorts, including fludarabine + cyclophosphamide + rituximab (FCR), bendamustine + rituximab (BR), Bruton tyrosine kinase inhibitor (BTKi)-based regimens, and venetoclax-based regimens.

Among 1364 patients who initiated first-line therapy, 13.9% received FCR, of whom 23.7% discontinued; 18.7% received BR, of whom 34.5% discontinued; 34.7% received BTKi-based regimens, of whom 28.1% discontinued; and 3.2% received venetoclax-based regimens, of whom 16.3% discontinued. The most common reasons for discontinuation were adverse events (13.2% with FCR, 14.1% with BR, and 15.9% with BTKi-based regimens) and disease progression (7% with venetoclax-based regimens).

Among 626 patients who initiated second-line therapy, 3.2% received FCR, and 50% discontinued; 9.9% received BR, and 35.5% discontinued; 48.4% received BTKi-based regimens, and 38% discontinued; and 11.7% received venetoclax-based regimens, and 30.1% discontinued. The main reason for discontinuation was adverse events: 30% with FCR, 17.7% with BR, 19.8% with BTKi-based regimens, and 8.2% with venetoclax-based regimens.

“The lowest proportion of patients that discontinued treatment prematurely were of the venetoclax-based regimen cohort,” researchers wrote, “potentially suggesting that venetoclax could be better tolerated than other agents, consistent with literature from clinical trials; however, larger cohorts of patients will be needed to confirm these findings in a broader population.”

Reference:
Shadman M, Manzoor BS, Sail K, et al. Treatment discontinuation patterns for patients with chronic lymphocytic leukemia in real-world settings: results from a multi-center international study. Clin Lymphoma Myeloma Leuk. Published online March 24, 2023. doi: 10.1016/j.clml.2023.03.010