Duvelisib, a first-in-class oral dual PI3K-δ,γ inhibitor, is approved for treatment of R/R CLL/SLL after ≥2 prior therapies. In the phase 3 DUO trial, duvelisib 25 mg BID significantly improved efficacy vs ofatumumab in patients with R/R CLL/SLL. Treatment-emergent AEs (TEAEs) of special interest (AESIs) were moderate and manageable with early intervention and dose modification.
To examine dose modification patterns and their impact on response to duvelisib in the DUO trial.
Dose interruptions (DIs) or reductions (DRs) were permitted per study protocol to manage TEAEs. Responses were assessed by IRC.
Among 158 duvelisib-treated patients, median duration of exposure was 11.6 months. DIs occurred more frequently than DRs (80% vs 27%). The most common AESIs leading to DI were diarrhea/colitis (28%), infections (27%), cutaneous reactions (13%), and neutropenia (12%). Among 118 responders, median time to first response was 1.9 months and median duration of response was 11.1 months. Median time to first DI was 3.9 months and median duration was 15 days. Response to duvelisib was improved or maintained in most patients evaluated for response who had ≥1 DI for >1 week (84%) or >2 weeks (82%) followed by ≥3 weeks on duvelisib. In a landmark analysis, median PFS was similar in patients with and without DI for >1 week (17.8 vs 16.3 months) or >2 weeks (17.8 vs 16.3 months) within the first 3 months. The median time to DR after CR/PR was 5.6 months (n=25) and median duration was 3.4 months. Median time to onset across AESIs ranged from 2.2 to 4.3 months and median duration across AESIs was up to 4 weeks. Proportions of patients experiencing AESIs were stable or decreased over time after 3-6 months: 0-3 months, 64%; >3-6 months, 63%; >6-9 months, 47%; >9-12 months, 52%, and seldom led to discontinuation of duvelisib (≤10%).
DIs/DRs can contribute to the effective management of TEAEs with duvelisib. These findings suggest that DIs of >1 week do not negatively impact response to duvelisib or PFS.
- Dose Modifications
- chronic lymphocytic leukemia