Managing Toxicity With Duvelisib in CLL: Dose Reductions or Interruptions
Posted: Thursday, September 5, 2019
Duvelisib, an approved first-in-class dual PI3K-delta, gamma inhibitor to treat relapsed or refractory chronic lymphocytic leukemia (CLL) or small lymphocytic lymphoma after at least two prior therapies, has been associated with numerous treatment-emergent adverse events. But findings from the DUO trial, presented at the 2019 American Society for Clinical Oncology (ASCO) Annual Meeting (Abstract 7523), showed that moderate dose interruptions and reductions to help manage these effects do not seem to significantly impact response or progression-free survival.
Among the treatment-emergent adverse events ideally addressed or avoided were infections, diarrhea, colitis, neutropenia, rash, ALT/AST elevation, and pneumonitis, noted Ian Flinn, MD, of Sarah Cannon Research Institute, Nashville, and colleagues. In the 158-patient phase III DUO trial, dosage reductions to 15, 10, or 5 mg of duvelisib twice daily were reviewed, as were dose interruptions (median length, 15 days; range, 1–133 days). Dose interruptions and reductions occurred in 80% and 27% of patients, respectively, and the median duration of response among all patients was 11.1 months.
The authors revealed that “a landmark analysis” showed “median progression-free survival was similar in patients with…and…without dose interruption for at least 1 week (17.8 vs. 16.3 months) or 2 weeks (17.8 vs. 16.3 months) within the first 3 months.” Similarly, “response to duvelisib was improved or maintained in most patients evaluated for response who had at least 1 dose interruption for more than 1 week (84%) or more than 2 weeks (82%) followed by at least 3 weeks on duvelisib,” wrote Dr. Flinn and co-investigators. Ultimately, fewer than 10% of patients discontinued duvelisib because of adverse events.
Disclosure: The study authors’ disclosure information may be found at coi.asco.org.