The dual inhibitor of PI3K-delta and PI3K-gamma, duvelisib, significantly improved progression-free survival (PFS) by more than 3 months compared with ofatumumab (median 13.3 months vs 9.9 months; hazard ratio [HR] = 0.52; P < .0001) in patients with relapsed or refractory chronic lymphocytic leukemia (CLL) and small lymphocytic leukemia (SLL), according to results from the phase 3 DUO study.1
Most current therapies for CLL/SLL are not curative, leaving an urgent need for the development of new, effective treatment options. Duvelisib targets key signaling pathways involved in the growth and survival of hematologic malignancies.
In this phase 3 study, 319 patients were randomly assigned to receive treatment with oral duvelisib 25 mg twice daily (160 individuals) or to IV ofatumumab (159 individuals).
At a median follow-up of 22.4 months, the median PFS (judged per an Independent Review Committee) was 13.3 months for duvelisib compared with 9.9 months for ofatumumab (HR = 0.52; P < .0001). Duvelisib also significantly improved PFS in patients with high-risk chromosome 17p13.1 deletions (del[17p]) and/or TP53 mutations (HR = 0.40; P = .0001).
Treatment with duvelisib resulted in an overall response rate of 74% compared with 45% for ofatumumab (P < .0001), regardless of del(17p) status.
Patients assigned to receive duvelisib had approximately twice the treatment exposure. The most common adverse events associated with duvelisib and ofatumumab were neutropenia, anemia, and thrombocytopenia, as well as diarrhea, pyrexia, nausea, and cough.
Based on the trial results, the researchers concluded that “duvelisib monotherapy may offer an effective treatment for CLL/SLL patients in need of additional therapeutic options.”
- Flinn IW, Hillmen P, Montillo M, et al. The phase 3 DUO trial: duvelisib versus ofatumumab in relapsed and refractory CLL/SLL [published online October 4, 2018]. Blood. doi: 10.1182/blood-2018-05-850461