The FDA has approved the PI3K inhibitor duvelisib for the treatment of patients with relapsed or refractory chronic lymphocytic leukemia (CLL) or small lymphocytic lymphoma (SLL) who have received at least two prior therapies.
The agency’s decision is based on results from the randomized, multicenter, open-label phase III DUO trial, in which patients were treated with either oral duvelisib 25 mg twice daily (n=95) or intravenous ofatumumab (n=101). Compared with ofatumumab, treatment with duvelisib was associated with longer median progression-free survival (16.4 months vs. 9.1 months; p value not provided) and a higher overall response rate (ORR; 78% vs. 39%; p value not provided).
The drug also received accelerated approval for adult patients with relapsed or refractory follicular lymphoma (FL) who have received two prior systemic therapies, based on results from the single-arm, multicenter DYNAMO trial. Among 83 patients with FL that was refractory to rituximab and either chemotherapy or radioimmunotherapy, duvelisib was associated with an ORR of 42 percent. Of the 35 patients who responded to duvelisib, 15 (43%) maintained responses for at least 6 months and six (17%) maintained responses for at least 12 months. The FDA noted that continued approval for the FL indication is contingent upon results from a planned randomized trial.
Safety information was available for 442 patients with hematologic malignancies who were treated with duvelisib at the approved dose. Sixty-five percent experienced serious adverse events (AEs), most frequently infection, diarrhea or colitis, and pneumonia. The most common any-grade AEs were diarrhea or colitis, neutropenia, rash, fatigue, pyrexia, cough, nausea, upper respiratory infection, pneumonia, musculoskeletal pain, and anemia. The prescribing information contains boxed warnings for fatal and/or serious infections, diarrhea or colitis, cutaneous reactions, and pneumonitis, as well as warnings for neutropenia and hepatotoxicity.
Source: FDA press release, September 24, 2018; Business Wire, September 24, 2018.