Ohashi Takuma, Takase-Minegishi Kaoru, Maeda Ayaka, Hamada Naoki, Yoshimi Ryusuke, Kirino Yohei, Teranaka Hiroshi, Kunimoto Hiroyoshi, Hagihara Maki, Matsumoto Kenji, Namkoong Ho, Horita Nobuyuki, Nakajima Hideaki
Department of Stem Cell and Immune Regulation, Yokohama City University Graduate School of Medicine, Yokohama, Japan.
Department of Infectious Diseases, Keio University School of Medicine, Tokyo, Japan.
J Hematol. 2023 Apr;12(2):66-74. doi: 10.14740/jh1090. Epub 2023 Apr 30.
Immune checkpoint inhibitors (ICIs) have been a breakthrough in cancer therapy. ICI therapy is generally better tolerated than cytotoxic chemotherapy; however, hematological adverse events (AEs) have not been fully analyzed. Hence, we performed a meta-analysis to evaluate the incidence and risk of ICI-related hematological AEs.
A systematic literature search was performed using PubMed, EMBASE, Cochrane Library, and the Web of Science Core Collection. Phase III randomized controlled trials (RCTs) involving ICI combination regimens were selected. The experimental group received ICIs with systemic treatment, and the control group received only the same systemic treatment. Odds ratios (ORs) for anemia, neutropenia, and thrombocytopenia were calculated using a random-model meta-analysis.
We identified 29 RCTs with 20,033 patients. The estimated incidence rates for anemia of all grades and grades III-V were 36.5% (95% confidence interval (CI) 30.23 - 42.75) and 4.1% (95% CI 3.85 - 4.42), respectively. The incidence of neutropenia (all grades 29.7%, grades III-V 5.3%) and thrombocytopenia (all grades 18.0%, grades III-V 1.6%) was also calculated.
Treatment with ICIs seemed unlikely to increase the incidence of anemia, neutropenia, and thrombocytopenia in all grades. However, programmed cell death-1 receptor ligand inhibitors significantly increased the risk of grades III-V thrombocytopenia (OR 1.53; 95% CI 1.11 - 2.11). Further research is needed to examine the potential risk factors.
免疫检查点抑制剂(ICIs)是癌症治疗领域的一项突破。ICI治疗通常比细胞毒性化疗耐受性更好;然而,血液学不良事件(AEs)尚未得到充分分析。因此,我们进行了一项荟萃分析,以评估ICI相关血液学AEs的发生率和风险。
使用PubMed、EMBASE、Cochrane图书馆和科学网核心合集进行系统的文献检索。选择涉及ICI联合方案的III期随机对照试验(RCTs)。实验组接受ICI联合全身治疗,对照组仅接受相同的全身治疗。使用随机模型荟萃分析计算贫血、中性粒细胞减少和血小板减少的比值比(ORs)。
我们纳入了29项RCTs,共20,033例患者。所有级别和III - V级贫血的估计发生率分别为36.5%(95%置信区间(CI)30.23 - 42.75)和4.1%(95%CI 3.85 - 4.42)。还计算了中性粒细胞减少(所有级别29.7%,III - V级5.3%)和血小板减少(所有级别18.0%,III - V级1.6%)的发生率。
ICI治疗似乎不太可能增加所有级别贫血、中性粒细胞减少和血小板减少的发生率。然而,程序性细胞死亡-1受体配体抑制剂显著增加了III - V级血小板减少的风险(OR 1.53;95%CI 1.11 - 2.11)。需要进一步研究以检查潜在的风险因素。