The FDA has now granted regular approval to duvelisib (Copiktra®, Verastem, Inc.) as a third-line or later treatment for adults with relapsed or refractory chronic lymphocytic leukemia (CLL)/small lymphocytic lymphoma (SLL). The FDA has also granted duvelisib accelerated approval as a third-line or later treatment for adults with relapsed or refractory follicular lymphoma (FL). Both CLL/SLL and FL are slow-growing types of non-Hodgkin lymphoma characterized by high rates of relapse, with limited options for later lines of therapy.
Regular approval for CLL/SLL was based on the DUO study (NCT02004522), a randomized, multicenter, open-label trial of 196 patients with CLL/SLL who had received at least 2 prior therapies. Duvelisib produced a median progression-free survival of 16.4 months, compared with 9.1 months for ofatumumab (Arzerra®, Novartis). The overall response rate was 78% for duvelisib versus 39% for ofatumumab.
Accelerated approval for FL patients was based on the DYNAMO + R study (NCT02204982), a single-arm, multicenter trial comprising 83 patients with FL refractory to rituximab and to either chemotherapy or radioimmunotherapy. Duvelisib produced an overall response rate of 42%, with 41% of patients experiencing partial response and one patient experiencing a complete response. Of the responding patients, 43% maintained responses for at least 6 months, and 17% maintained responses for at least 12 months. Continued approval for the use of duvelisib in FL may depend on verification of clinical benefit in a planned randomized trial.
The approved dose of duvelisib—25 mg administered orally twice daily, taken continuously in 28-day treatment cycles—produced serious adverse reactions in 65% of 442 patients with hematologic malignancies. The most common adverse reactions, occurring in at least 20% of patients, included diarrhea or colitis, neutropenia, rash, fatigue, pyrexia, cough, nausea, upper respiratory infection, pneumonia, musculoskeletal pain, and anemia. Adverse reactions led to dose reduction in 24% of patients and permanent discontinuation in 35%. The prescribing information includes boxed warnings for serious or fatal infections, diarrhea or colitis, cutaneous reactions, and pneumonitis. It also contains warnings for neutropenia and hepatotoxicity.
"[Duvelisib] is an important addition to the evolving treatment paradigm for patients with CLL/SLL and follicular lymphoma," stated Ian Flinn, MD, PhD, director of the Lymphoma Research Program at Sarah Cannon Research Institute and lead investigator of the DYNAMO and DUO studies. "I believe [it] will address an unmet need for patients who have limited options once they have progressed after two prior therapies."
For More Information
Clinicaltrials.gov (2018). A phase 3 study of duvelisib versus ofatumumab in patients with relapsed or refractory CLL/SLL (DUO). NLM identifier: NCT02004522.
Clinicaltrials.gov (2018). Study of duvelisib in combination with rituximab vs rituximab in subjects with previously treated follicular lymphoma (DYNAMO + R). NLM identifier: NCT02204982.