FDA Warns About Possible Increased Risk of Death and Serious Side Effects With Duvelisib

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The U.S. Food and Drug Administration (FDA) is warning that results from the phase III DUO clinical trial show a possible increased risk of death with duvelisib compared to ofatumumab among patients with chronic lymphocytic leukemia (CLL) or small lymphocytic lymphoma (SLL). The trial also found duvelisib was associated with a higher risk of serious side effects, including infections, diarrhea, inflammation of the intestines and lungs, skin reactions, and high liver enzyme levels in the blood.

The FDA is notifying the public of these risks and continuing to evaluate the safety of duvelisib. The agency is planning to hold a future public meeting to discuss the findings from the clinical trial and whether duvelisib should continue to be prescribed for patients.

Duvelisib was approved in 2018 to treat adults with CLL or SLL who have received at least two prior therapies. With the approval in 2018, the information on survival or risk of death was limited, and the FDA required longer follow-up from the DUO trial to gain more information

Patients should talk to their health-care providers about the risks and benefits of receiving duvelisib. Health-care professionals should consider the risks and benefits of continuing duvelisib in the context of other available treatments and advise patients receiving duvelisib of the possible increased risk of death and higher risk of serious adverse events.

To help the FDA track safety issues with medicines, patients and health-care professionals are urged to report side effects involving duvelisib or other medicines to the FDA MedWatch program.

More About the DUO Trial

Duvelisib was approved in 2018 based on the benefit-risk evaluation of data available at the time from the DUO trial for patients with relapsed or refractory CLL or SLL who had received at least two prior lines of therapy. The DUO trial was a phase III, randomized, open-label trial that evaluated duvelisib vs ofatumumab in 319 patients with relapsed or refractory CLL or SLL who received at least one prior line of therapy. The primary endpoint was progression-free survival.

At the time of initial approval, the overall survival information was limited, and the FDA required the manufacturer to submit the final analysis of overall survival at 5 years in the trial to enable the evaluation of duvelisib’s long-term safety. With a median of 63 months of follow-up, the final overall survival results showed a possible increased risk of death with duvelisib, with a hazard ratio of 1.09 (95% confidence interval [CI] = 0.79–1.51).

Among the subpopulation of patients receiving at least two prior lines of therapy—the FDA-approved use—the hazard ratio was 1.06 (95% CI = 0.71–1.58). In addition to the risk of death, the incidence of deaths due to adverse events, serious adverse events, grade ≥ 3 adverse events, and treatment modifications due to adverse events were higher among patients receiving duvelisib. These safety findings were similar for other medicines in the same PI3 kinase inhibitor class, which were discussed at an advisory committee meeting of non-FDA experts in April 2022.

The content in this post has not been reviewed by the American Society of Clinical Oncology, Inc. (ASCO®) and does not necessarily reflect the ideas and opinions of ASCO®.