On June 30, 2022, the U.S. Food and Drug Administration issued a drug safety communication for duvelisib (Copiktra®) after results from a clinical trial showed a possible increased risk of death associated with the agent, which is approved for the treatment of adult patients with relapsed or refractory chronic lymphocytic leukemia (CLL) or small lymphocytic lymphoma (SLL who have received at least two prior therapies. The clinical trial results also associated duvelisib with a higher risk of serious side effects, including infections, diarrhea, lung and intestinal inflammation, skin reactions, and elevated liver enzymes.

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

Duvelisib is classified as an oral PI3 kinase inhibitor. In the safety communication, FDA advised healthcare professionals to consider the risks and benefits of continuing duvelisib if other treatments are available and to advise patients receiving the agent about the possible increased risk of death and serious adverse events.

Patients should talk to their healthcare professionals about their individual risks and benefits with duvelisib. FDA recommended that patients discuss any questions or concerns, including possible alternative treatment options, with their cancer care team.

Duvelisib was approved in 2018 to treat adults with CLL or SLL whose cancers became refractory to at least two prior therapies after clinical trials comparing it to the monoclonal antibody ofatumumab found a 78% overall response rate with duvelisib versus 39% with ofatumumab.

Duvelisib’s clinical trials continued after the approval because FDA required longer follow-up to gain more information about the drug’s influence on survival or risk of death. FDA based the June 2022 safety communication and its recommendations on the final five-year survival results from the DUO trial, a phase III, randomized, open-label trial conducted in 319 patients with CLL or SLL who received a previous therapy that did not work or stopped working. The trial’s results showed a possible increased risk of death with duvelisib compared to the monoclonal antibody ofatumumab. The rate of serious side effects, dose modifications, and deaths resulting from these side effects were also higher among patients receiving duvelisib, including infections (31%, 4% fatal), diarrhea (18%, < 1% fatal), lung and intestinal inflammation (5%, < 1% fatal), skin reactions (5%, < 1% fatal), and elevated liver enzymes.

FDA encouraged patients and providers to report any side effects involving duvelisib or other medications to the MedWatch Reporting System or by calling 800-FDA-1088.