Adverse events in lymphoma patients treated with phosphoinositide 3 kinase Inhibitor in clinical trials: a meta-analysis

Abstract

Background: Malignant lymphomas are one of the most common cancers worldwide and with high biologic heterogeneity, while the phosphoinositide 3 kinase (PI3K)/mTOR pathway is crucial in maintaining cell growth and survival both in physiological and in pathological conditions (i.e., lymphoma). PI3K inhibitors have been proven to be effective in several subtypes of lymphomas. However, the high incidence of treatment-related adverse events as well as the special safety profile in PI3K inhibitors draws great attention. Thus, this meta-analysis was conducted to compare adverse events in PI3K inhibitors to conventional regimens in lymphoma patients.

Methods: Articles were retrieved from PubMed, Cochrane, and Embase to identify randomized controlled trials and phase III clinical trials that used PI3K inhibitors comparing with non-PI3K inhibitors in lymphoma patients. To achieve the appropriate results, we calculated the risk ratio and 95% confidence intervals.

Results: Four trials with 1399 patients that met our criteria were included. The PI3K inhibitors group significantly increased the risk of all-grade adverse events (AEs) (RR 0.95, 95% CI: 0.92-0.98) and high-grade AEs (RR 0.63, 95% CI: 0.57-0.70), compared with the non-PI3K inhibitors group. Besides, the incidence of neutropenia (RR 0.81, 95% CI: 0.74-0.90), pneumonia (RR 0.62, 95% CI: 0.46-0.83), and diarrhea (RR 0.40, 95% CI: 0.32-0.49) were significantly high in the PI3Ki group, while the incidence of anemia (RR 0.78, 95% CI: 0.50-1.20) and thrombocytopenia (RR 0.85, 95% CI: 0.51-1.42) had no statistic significant.

Conclusion: PI3K inhibitors increased the risk of certain AEs in lymphoma patients.

Keywords: Adverse event; Lymphoma patients; Meta-analysis; Phosphoinositide 3 kinase inhibitors.