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Life sciences · Journal article
Journal of Clinical Medicine · August 14, 2026
A consensus or society position rather than new primary data.
This systematic review synthesizes 130 studies on hematological immune-related adverse events (Hem-irAEs) in modern melanoma therapy, reporting rare but severe toxicities with mortality rates of 12–15.5% despite low overall incidence (<4% for ICIs). The evidence supports clinical guidance on risk stratification, diagnosis via bone marrow biopsy, and management escalation from corticosteroids to targeted immunosuppressants, but derives from aggregated observational and trial data rather than a single definitive trial.
Systematic literature review. Studies reporting hematological adverse events in patients receiving immune checkpoint inhibitors or targeted therapies for melanoma. Intervention: Immune checkpoint inhibitors and targeted therapies for melanoma.
Hem-irAEs occur infrequently (under 4% overall incidence for ICIs) but possess mortality rates between 12% and 15.5% Most common manifestations are immune thrombocytopenia (ITP), autoimmune hemolytic anemia, and neutropenia Combination regimens significantly amplify toxicity frequency and severity
Review does not report individual study quality scores or meta-analytic pooling; incidence and mortality figures are synthesized narratively across 130 heterogeneous studies No relative risk, hazard ratio, or confidence intervals reported for comparative toxicity between mono- and combination therapy
Clinicians should implement proactive baseline monitoring and bone marrow biopsy capability to diagnose hematological irAEs early, and be prepared to discontinue immunotherapy and initiate high-dose corticosteroids urgently. Risk stratification using autoantibodies, HLA profiling, and inflammatory indices is recommended to identify vulnerable patients before treatment initiation.
A systematic literature review synthesizing evidence on hematological immune-related adverse events in melanoma immunotherapy, providing clinical guidance on incidence, diagnosis, and management rather than reporting original trial data.
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Clinicians should implement proactive baseline monitoring and bone marrow biopsy capability to diagnose hematological irAEs early, and be prepared to discontinue immunotherapy and initiate high-dose corticosteroids urgently. Risk stratification using autoantibodies, HLA profiling, and inflammatory indices is recommended to identify vulnerable patients before treatment initiation.
Graded across the dimensions that decide whether you should act, each from what the source actually supports. There is no single score, and where a dimension was not assessed it says so.
Background/Objectives: The advent of immune checkpoint inhibitors (ICIs) and targeted therapies has revolutionized advanced melanoma treatment but introduced unique immune-related adverse events (irAEs). Hematological irAEs (Hem-irAEs) are rare but carry disproportionately high morbidity and mortality. This review systematically synthesizes current literature to comprehensively understand the incidence, pathophysiology, clinical presentation, and management of Hem-irAEs in modern melanoma therapy. Methods: A comprehensive Web of Science literature search (January 2015 to January 2026) identified studies reporting hematological adverse events associated with melanoma immunotherapy and targeted therapies. After screening 2274 records, 130 relevant studies were included for quantitative data extraction, focusing on incidence rates and toxicity grading. Results: Hem-irAEs occur infrequently (under 4% overall incidence for ICIs) but possess staggering mortality rates between 12% and 15.5%. The most common manifestations are immune thrombocytopenia (ITP), autoimmune hemolytic anemia, and neutropenia. Combination regimens significantly amplify toxicity frequency and severity. Diagnosis requires meticulous baseline monitoring and bone marrow biopsies to differentiate peripheral destruction from central marrow failure. First-line management mandates ICI discontinuation and high-dose corticosteroids, utilizing targeted second-line immunosuppressants for refractory syndromes. Conclusions: Hem-irAEs embody a profound clinical paradox: while mild toxicities often herald a robust anti-tumor response, severe hematological events drastically increase non-cancer mortality, negating these oncological benefits. Navigating this “double-edged sword” demands a paradigm shift toward proactive risk stratification. Integrating predictive biomarkers including baseline autoantibodies, Human Leukocyte Antigens (HLA) profiling, and systemic inflammatory indices is crucial to identify vulnerable populations before treatment. Optimizing outcomes requires highly personalized vigilance to balance the life-saving efficacy of immunotherapy against the catastrophic threat of hematopoietic failure.
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