FDA Expresses Caution About Increased Risk of Death, Serious AEs Associated With Duvelisib in CLL/SLL

The regulatory organization indicated that duvelisib induces increased risk of death or serious adverse effects in patients with chronic lymphocytic leukemia and small lymphocytic leukemia.

Findings from a clinical trial indicated that PI3K inhibitor duvelisib (Copiktra) could lead to an increased risk of death and serious adverse effects (AEs) in patients with chronic lymphocytic leukemia (CLL) and small lymphocytic leukemia (SLL), according to a press release from the FDA.1

In particular, the agent was found to be associated with serious AEs such as infections, diarrhea, inflammation of the intestines/lungs, skin reactions, and elevated liver enzymes. Practitioners have been advised by the FDA to consider the risks and benefits of duvelisib before continuing treatment with the agent, as well as cautioning patients about the potential increased risk of serious AEs or death.

Findings from the phase 3 DUO trial (NCT02004522), which compared the use of duvelisib with ofatumumab (Kesimpta) in patients with relapsed/refractory CLL or SLL who had at least 1 previous therapy (n = 319), highlighted a potential increased risk of death in the experimental arm.2 However, when initial results of the trial were published, investigators indicated that progression-free survival (PFS) and overall response rate (ORR) were significantly improved in the duvelisib arm compared with the ofatumumab arm. The median PFS was 13.3 months compared with 9.9 months in each respective arm (HR, 0.52; P <.0002). Moreover, the ORR in the experimental arm was 74% compared with 45% in the ofatumumab arm (P <.0001).

In the study, patients were randomized 1:1 to receive either duvelisib at a dose of 25 mg twice daily or intravenous ofatumumab.

Duvelisib was approved by the FDA in September 2018 for the treatment of adult patients with relapsed/refractory CLL/SLL.3 This marked the first approval of a dual inhibitor of PI3K-delta and PI3K-gamma.

In December 2021, developer Secura Bio announced a voluntary withdrawal of the agent’s indication for the treatment of relapsed/refractory follicular lymphoma following discussion with the FDA.4 Together, the 2 bodies determined that within the present treatment landscape for this patient population, the logistics, costs, and timing necessary for post-marketing requirements was no longer warranted. Notably, the decision was not related to any changes with efficacy or safety of the drug.


  1. FDA warns about possible increased risk of death and serious side effects with cancer drug Copiktra (duvelisib). News release. FDA. June 30, 2022. Accessed July 11, 2022. https://bit.ly/3PAlZLl
  2. Flinn IW, Hillmen P, Montillo M, et al. The phase 3 DUO trial: duvelisib vs ofatumumab in relapsed and refractory CLL/SLL. Blood. 2018;132(23):2446-2455. doi:10.1182/blood-2018-05-850461
  3. Verastem Oncology receives FDA approval of COPIKTRA™ (duvelisib) capsules. News released. September 24, 2018. Accessed July 11, 2022. https://bit.ly/3P2iH3q
  4. Secura Bio announces Copiktra® (duvelisib) strategic focus on T-cell lymphoma and voluntary U.S. withdrawal of the relapsed or refractory follicular lymphoma indication. News release. Secura Bio. December 3, 2021. Accessed July 11, 2022. https://prn.to/3arGI4P