Abstract
Immune-related hematological adverse events are amongst the rare but potentially life-threatening complications of immune checkpoint inhibitors. The spectrum of these toxicities is broadening as the number of patients exposed to these agents is increasing. Yet, they are still relatively unknown to many clinicians, possibly due to a lack of specific diagnostic criteria, which poses a challenge for their recognition and proper reporting, and partly due to their low incidence, often too low to be noted in most clinical trial publications. Since early detection and prompt intervention are crucial to prevent fatal consequences, it is of outmost importance that medical staff and patients be aware of these potential toxicities and learn to recognize and treat them adequately. This publication outlines strategies and offers guidance on the detection, diagnosis, risk assessment, monitoring and management of immune-related thrombocytopenia, a relatively common example of immune-related hematological toxicity of immune checkpoint inhibitors.
Highlights
With the increasing number of approved Immune checkpoints inhibitors (ICIs), new indications, and number of patients exposed to them, the repertoire of hematological immune-related adverse events (ir-AEs) extends to entities as varied as pure red cell aplasia (Gordon et al, 2009; Nair et al, 2016; Yuki et al, 2017), aplastic anemia/bone marrow failure (Comito et al, 2017; Michot et al, 2017; Helgadottir et al, 2017; Meyers et al, 2018), hemophilia A (Delyon et al, 2011; Lozier, 2012), acute thrombosis (Kunimasa et al, 2018), large granular lymphocytosis (Wei et al, 2012), hemophagocytic lymphohistiocytosis (Sadaat and Jang, 2018), macrophage activation syndrome (Malissen et al, 2017), eosinophilia (Bernard-Tessier et al, 2017), and hematological cytopenias affecting one or more hematological cell lines
This review focuses on ir-TCP as the most common type of hem-irAEs along with autoimmune hemolytic anemia and neutropenia, each occurring in 26% of patients with a reported hem-irAE during PD-1/PD-L1 treatment registered in three French pharmacovigilance databases (Delanoy et al, 2019)
Upregulation of PD-1 expression on B-cells prior to ICI treatment (Kanameishi et al, 2016), the detection of autoantibodies (Le Burel et al, 2017), and the presence of specific single nucleotide polymorphisms of PD-1 and CTLA4 possibly associated with certain autoimmune diseases including immune thrombocytopenic purpura (ITP) (e.g., PD-1 +7209 C/T SNP and an increased susceptibility to ITP, CTLA4 -1577 A/G and CT60 A/G associated with ITP severity, and PD-D1 -606 G/A and +63379 C/T associated with the patient’s ITP response to prednisolone) (Kasamatsu et al, 2018), have been postulated as potential biomarkers
Summary
Immune-related hematological adverse events are amongst the rare but potentially life-threatening complications of immune checkpoint inhibitors. The spectrum of these toxicities is broadening as the number of patients exposed to these agents is increasing. They are still relatively unknown to many clinicians, possibly due to a lack of specific diagnostic criteria, which poses a challenge for their recognition and proper reporting, and partly due to their low incidence, often too low to be noted in most clinical trial publications. This publication outlines strategies and offers guidance on the detection, diagnosis, risk assessment, monitoring and management of immune-related thrombocytopenia, a relatively common example of immune-related hematological toxicity of immune checkpoint inhibitors
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