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.
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.”
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