Hematological toxicities in immune checkpoint inhibitors: A pharmacovigilance study from 2014 to 2019

Abstract

Immune checkpoint inhibitors (ICIs) have shown remarkable clinical effects in many cancer types. However, ICIs could also induce severe organ system toxicities, including those of the hematological system. The present study aimed to extensively characterize the hematological toxicities of ICIs immunotherapy. Data were extracted from the US Food and Drug Administration Adverse Event Reporting System (FAERS) database from January 1, 2014, to March 31, 2019. Disproportionality analysis, including information component (IC) and reporting odds ratio (ROR), was used to detect potential disproportionality signal. The lower boundary of the 95% confidence interval of IC (IC 025) exceeding zero or that of ROR (ROR 025) exceeding one was considered statistically significant for detecting disproportionality signal. A total of 29 294 335 records were extracted from the database, with 132 573 related to ICIs. Overall, hematological adverse events (AEs) were more frequently reported in ICIs (IC 025 : 0.81; ROR 025 : 1.80). On further analysis, hematological AEs were overreported in female patients (female vs male, ROR 025 : 1.04) and anti-CTLA-4 monotherapy groups (anti-CTLA-4 vs anti-PD-1, ROR 025 : 1.33) and polytherapy groups (polytherapy vs monotherapy, ROR: 1.20, ROR 025 : 1.11). Moreover, class-specific hematological AEs were also detected and differed in unique ICI regimens. Notably, disseminated intravascular coagulation had the highest proportion of death outcomes among the top 10 most frequently reported ICI-associated hematological AEs. Our study shows a high reporting frequency of hematological AEs induced by ICI monotherapy (especially by anti-CTLA-4 therapy) and reinforced by polytherapy. A spectrum of class-specific disproportionality signal was also detected; some were fatal and reported for the first time. The heterogeneous clinical spectrum of hematological toxicities, including the non-negligible proportion of death as reported outcome, are warranted to be reminded by clinicians. Early recognition and management of ICIrelated hematological AEs are highly important and further studies are needed to confirm the results of our study.

Cardiovascular Toxicity of Carfilzomib: The Real-World Evidence Based on the Adverse Event Reporting System Database of the FDA, the United States

“…It has been proved that the statistical shrinkage can protect against spurious associations and obtain robust results. In recent years, this statistical technique has been applied more and more in signal detection of adverse drug reactions (11,(17)(18)(19). In the present study, the shrunk IC and ROR were calculated as:…”

Nephrotoxicity of Immune Checkpoint Inhibitors: A Disproportionality Analysis from 2013 to 2020

“…To the best of our knowledge, this study is the the most systematic and comprehensive collection until recently to compare the associations of renal adverse effects after different ICIs in the realworld practice based on the FAERS pharmacovigilance database. Previous researches show that ICIs can increase the risk of organ system toxicities such as endocrine, hematological, ear and labyrinth toxicity (Zhai et al 2019;Ye et al 2020). Nephrotoxicity is rare.…”

Disseminated intravascular coagulation induced by pazopanib following combination therapy of nivolumab plus ipilimumab in a patient with metastatic renal cell carcinoma

“…With the advent of ICI, a host of immune-related adverse events are being described. Anti-CTLA-4 therapy is the most frequently reported ICI to cause hematological toxicities, and polytherapy increased the risk [28]. ICIs have the potential to disrupt hemostasis coagulation pathways as a result of an aggravated immune response [29][30][31].…”