Hematologic and lymphatic system toxicities associated with immune checkpoint inhibitors: a real-world study

Na Li; Yong Feng; XiaoLing Chen; Ye Li; Chengmiao Zhang; Yin Yin

doi:10.3389/fphar.2023.1213608

Hematologic and lymphatic system toxicities associated with immune checkpoint inhibitors: a real-world study

Front Pharmacol. 2023 Oct 31:14:1213608. doi: 10.3389/fphar.2023.1213608. eCollection 2023.

Authors

Na Li¹, Yong Feng², XiaoLing Chen³, Ye Li¹, Chengmiao Zhang¹, Yin Yin¹

Affiliations

¹ Department of Central Laboratory, Shenyang Tenth People's Hospital, Shenyang Chest Hospital, Shenyang, China.
² Department of Thoracic Surgery, Shenyang Tenth People's Hospital, Shenyang Chest Hospital, Shenyang, China.
³ Department of Pathology, Shenyang Tenth People's Hospital, Shenyang Chest Hospital, Shenyang, China.

Abstract

Introduction: Immune checkpoint inhibitors (ICIs) exert antitumor responses in many types of cancer but may also induce serious or fatal toxicities that affect all organ systems, including the hematologic and lymphatic systems. However, the risk of hematologic and lymphatic system toxicities following different ICI treatments remains unknown. This study aimed to describe the hematologic and lymphatic system toxicities associated with different ICI regimens and the impact of combining ICIs with anti-vascular endothelial growth factor drugs using the United States Food and Drug Administration Adverse Event Reporting System pharmacovigilance database. Methods: The reporting odds ratio (ROR) and information component (IC) indices were used to identify disproportionate reporting of ICI-associated hematologic and lymphatic adverse events (AEs). Results: We extracted 10,971 ICI-associated hematologic and lymphatic AEs from 35,417,155 reports. These AEs were more frequently reported in female patients (ROR: 1.04 95% confidence interval [CI]: 1.01-1.07) and younger patients (ROR: 1.05 95% CI: 1.01-1.09). The disseminated intravascular coagulation fatality rate (63.97%) was the highest among the reported preferred terms, despite its low incidence (3.32%). The time to onset of ICI-related hematologic and lymphatic AEs was relatively short, with 77.44% reported within 3 months. Disproportionate analysis showed that most ICIs were associated with significant overreporting of hematologic and lymphatic AEs (IC₀₂₅: 0.34 and ROR₀₂₅: 2.10). Hematologic and lymphatic system AEs were more frequently reported in patients treated with anti-programmed cell death protein 1/programmed cell death ligand 1 monotherapy than in those treated with anti-cytotoxic T-lymphocyte-associated protein 4 monotherapy (ROR: 1.54, 95% CI: 1.38-1.71), with atezolizumab showing the strongest signal (ROR₀₂₅: 4.19, IC₀₂₅: 1.00). In patients receiving combined treatment, ICIs plus bevacizumab exerted a higher disproportion signal than monotherapy (ROR: 161, 95% CI: 1.75-1.88). Discussion: The spectrum of hematologic and lymphatic AEs differed according to the ICI regimen. Early recognition and management of ICI-related hematologic and lymphatic AEs are vital in clinical practice.

Keywords: FDA adverse event reporting system; bevacizumab; combination therapy; cytotoxic T-lymphocyte-associated protein; hematologic and lymphatic toxicities; immune checkpoint inhibitors; monotherapy; programmed cell death protein 1/programmed cell death ligand 1.