Treatment With PI3K Inhibitors Is Associated With a Number of Adverse Events and Toxicities

Treatment with phosphatidylinositol 3-kinase (PI3K) inhibitors has been shown to improve survival in patients with B cell malignancies. However, according to a study results presented at the 61st American Society of Hematology (ASH) Annual Meeting & Exposition, held in Orlando, Florida, PI3K treatment is also associated with an increased incidence of adverse events including pneumonitis, Pneumocystis jiroveci pneumonia, any-grade upper respiratory tract infections, and sepsis.

PI3K plays an important role in B cell survival, proliferation, and metabolism. Two prominent PI3K inhibitors, idelalisib (PI3Kδ-selective inhibitor) and duvelisib (PI3Kδ/γ-combinatorial inhibitor), are currently being tested for the treatment of relapsed and refractory chronic lymphocytic leukemia or small lymphocytic lymphoma (CLL/SLL).

In the study, researchers evaluated available data from 1216 patients with CLL/SLL who had participated in phase 3 clinical trials comparing treatment with PI3K inhibitors to standard control therapy.

Overall, the PI3K inhibitor treatment had a higher incidence of serious adverse events compared with the control (73.69% vs 44.92%). The incidence of any grade pneumonia was 16.4% in the PI3K inhibitor group compared with 9.63% in the control group. PI3K inhibitor treatment was also associated a 2.24% higher rate of Pneumocystis jiroveci pneumonia.

Any grade upper respiratory tract infections were also higher in the PI3K inhibitor group compared with the control (14% vs 7.84%). The pooled risk ratio of sepsis in the PI3K inhibitor group was statistically significant at 2.68, with a 2.88% higher sepsis rate in the patients treated with the PI3K inhibitor, idelalisib.

Overall, the treatment related deaths across the 3 trials was 11.85% in the PI3K groups vs 6.17% in the control group. The authors advised, “Since treatment-related serious toxicities and deaths are higher amongst patients treated with these agents, extra caution should be observed and recommended with their use.”

Reference

Swarup S, Quick DP, Sultan A, et al. Incidence of serious adverse events, pneumonitis, infection and sepsis in patients with relapsed and refractory chronic lymphocytic leukemia/small lymphocytic lymphoma treated with phosphatidylinositol 3-Kinase (PI3K) inhibitors. Oral presentation at: 61st ASH Annual Meeting & Exposition; December 7-10, 2019; Orlando, FL. Abstract 798.