The FDA has warned that treatment with duvelisib has shown a possible increased risk of death and serious adverse effects compared with ofatumumab in patients with relapsed/refractory chronic lymphocytic leukemia and small lymphocytic lymphoma.
The FDA has warned that treatment with duvelisib (Copiktra) has shown a possible increased risk of death and serious adverse effects (AEs) compared with ofatumumab (Arzerra) in patients with relapsed/refractory chronic lymphocytic leukemia (CLL) and small lymphocytic lymphoma (SLL).1
The warning was based on 5-year survival results from the phase 3 DUO trial (NCT02004522). At a median follow-up of 63 months, data showed that duvelisib elicited a median overall survival (OS) of 52.3 months (95% CI, 41.8-68), compared with 63.3 months (95% CI, 41.2–not estimable) for ofatumumab (HR, 1.09; 95% CI, 0.79-1.51).
Notably, among patients with CLL and SLL who received at least 2 prior lines of treatment, which is the current FDA-approved use of duvelisib, the hazard ratio for death was 1.06 (95% CI, 0.71-1.58).
Additionally, duvelisib was associated with a higher incidence of deaths due to AEs, serious AEs, grade 3 or higher AEs, and treatment modifications. Regarding serious AEs, infections, diarrhea, inflammation of the intestine and/or lungs, skin reactions, and elevated liver enzymes all occurred at a higher frequency in patients who received duvelisib.
“Health care professionals should consider the risks and benefits of continuing [duvelisib] in the context of other available treatments. Advise patients receiving [duvelisib[ of the possible increased risk of death and higher risk of serious AEs,” the FDA wrote in a press release.
In September 2018, the FDA approved duvelisib for the treatment of patients with relapsed/refractory CLL and SLL or relapsed/refractory follicular lymphoma, based on findings from the DUO trial and the phase 2 DYNAMO trial (NCT01882803).2 However, in December 2021, Secura Bio withdrew the indication of duvelisib for relapsed/refractory follicular lymphoma in the United States.3
The randomized, open-label DUO trial enrolled 319 patients with relapsed/refractory CLL (n = 312) or SLL (n = 7) who had received at least 1 prior line of therapy. Patients were required to have hepatic transaminases of no more than 3 times the upper limit of normal (ULN), a total bilirubin of no more than 1.5 times the ULN, and serum creatinine of no more than 2 times the ULN.4 Patients who underwent autologous stem cell transplant within 6 months of enrollment or an allogeneic stem cell transplant at any point were excluded. Patients were also excluded if they had prior exposure to a PI3K inhibitor or a BTK inhibitor.
Once enrolled, patients were randomized 1:1 to received 25 mg of duvelisib twice daily until progressive disease or unacceptable toxicity, or ofatumumab for 7 cycles. Patients who were administered ofatumumab received an initial dose of 300 mg, followed by 2000 mg weekly for 7 doses, then 2000 mg weekly for 4 doses.
The primary end point of the trial was progression-free survival. Secondary end points included overall response rate, hematologic improvements, OS, lymph node response rate, duration of response, treatment-emergent AEs, and pharmacokinetics.