Department of Hematology, School of Medicine, The First Affiliated Hospital of Xiamen University and Institute of Hematology, Xiamen University, Xiamen, 361102, People's Republic of China.
Key Laboratory of Xiamen for Diagnosis and Treatment of Hematological Malignancy, Xiamen, 361102, People's Republic of China.
Ann Hematol. 2022 Aug;101(8):1741-1753. doi: 10.1007/s00277-022-04876-x. Epub 2022 Jun 11.
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.
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.
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.
PI3K inhibitors increased the risk of certain AEs in lymphoma patients.
恶性淋巴瘤是全球最常见的癌症之一，具有高度的生物学异质性，而磷酸肌醇 3 激酶（PI3K）/哺乳动物雷帕霉素靶蛋白（mTOR）途径在维持细胞生长和存活方面至关重要，无论是在生理条件下还是在病理条件下（即淋巴瘤）。PI3K 抑制剂已被证明在几种淋巴瘤亚型中有效。然而，治疗相关不良反应的高发率以及 PI3K 抑制剂的特殊安全性特征引起了极大关注。因此，进行了这项荟萃分析，以比较淋巴瘤患者使用 PI3K 抑制剂与常规方案的不良反应。
从 PubMed、Cochrane 和 Embase 中检索到使用 PI3K 抑制剂与非 PI3K 抑制剂比较治疗淋巴瘤患者的随机对照试验和 III 期临床试验。为了得出适当的结果，我们计算了风险比和 95%置信区间。
符合标准的四项试验共纳入 1399 名患者。与非 PI3K 抑制剂组相比，PI3K 抑制剂组发生所有级别不良反应（AE）（RR 0.95，95%CI：0.92-0.98）和高级别 AE（RR 0.63，95%CI：0.57-0.70）的风险显著增加。此外，中性粒细胞减少症（RR 0.81，95%CI：0.74-0.90）、肺炎（RR 0.62，95%CI：0.46-0.83）和腹泻（RR 0.40，95%CI：0.32-0.49）的发生率在 PI3Ki 组显著升高，而贫血（RR 0.78，95%CI：0.50-1.20）和血小板减少症（RR 0.85，95%CI：0.51-1.42）的发生率无统计学意义。
PI3K 抑制剂增加了淋巴瘤患者发生某些不良反应的风险。
