{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,14]],"date-time":"2026-08-14T11:32:20Z","timestamp":1786707140095,"version":"build-2736575974"},"reference-count":130,"publisher":"MDPI AG","issue":"16","license":[{"start":{"date-parts":[[2026,8,14]],"date-time":"2026-08-14T00:00:00Z","timestamp":1786665600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["J. Clin. Med.","JCM"],"abstract":"<jats:p>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 \u201cdouble-edged sword\u201d 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.<\/jats:p>","DOI":"10.3390\/jcm15166296","type":"journal-article","created":{"date-parts":[[2026,8,14]],"date-time":"2026-08-14T10:39:01Z","timestamp":1786703941000},"page":"6296","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Hematological Toxicities in the Modern Era of Melanoma Therapy"],"prefix":"10.3390","volume":"15","author":[{"given":"Rodica","family":"Anghel","sequence":"first","affiliation":[{"name":"Faculty of General Medicine, Carol Davila University of Medicine and Pharmacy, 8 Eroii Sanitari Street, 050474 Bucharest, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ana-Maria","family":"Zamfirescu-Deryder","sequence":"additional","affiliation":[{"name":"Faculty of General Medicine, Carol Davila University of Medicine and Pharmacy, 8 Eroii Sanitari Street, 050474 Bucharest, Romania"},{"name":"Oncological Institute \u201cAlexandru Trestioreanu\u201d Bucharest, 252 Soseaua Fundeni, 022328 Bucharest, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vlad-Luca","family":"Moga","sequence":"additional","affiliation":[{"name":"Faculty of General Medicine, Carol Davila University of Medicine and Pharmacy, 8 Eroii Sanitari Street, 050474 Bucharest, Romania"},{"name":"Oncological Institute \u201cAlexandru Trestioreanu\u201d Bucharest, 252 Soseaua Fundeni, 022328 Bucharest, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0000-3350-7850","authenticated-orcid":false,"given":"Antonia-Ruxandra","family":"Folea","sequence":"additional","affiliation":[{"name":"Faculty of General Medicine, Carol Davila University of Medicine and Pharmacy, 8 Eroii Sanitari Street, 050474 Bucharest, Romania"},{"name":"Oncological Institute \u201cAlexandru Trestioreanu\u201d Bucharest, 252 Soseaua Fundeni, 022328 Bucharest, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Radu-Valeriu","family":"Toma","sequence":"additional","affiliation":[{"name":"Faculty of General Medicine, Carol Davila University of Medicine and Pharmacy, 8 Eroii Sanitari Street, 050474 Bucharest, Romania"},{"name":"Oncological Institute \u201cAlexandru Trestioreanu\u201d Bucharest, 252 Soseaua Fundeni, 022328 Bucharest, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andreea-Iren","family":"\u0218erban","sequence":"additional","affiliation":[{"name":"Faculty of Biology, University of Bucharest, 91-95 Splaiul Independentei, 050095 Bucharest, Romania"},{"name":"Department of Preclinical Sciences, Faculty of Veterinary Medicine, University of Agronomic Sciences and Veterinary Medicine, 105 Splaiul Independentei, 050097 Bucharest, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Liviu","family":"B\u00eelteanu","sequence":"additional","affiliation":[{"name":"Faculty of General Medicine, Carol Davila University of Medicine and Pharmacy, 8 Eroii Sanitari Street, 050474 Bucharest, Romania"},{"name":"Faculty of Biology, University of Bucharest, 91-95 Splaiul Independentei, 050095 Bucharest, Romania"},{"name":"Laboratory for Molecular Nanotechnologies, National Institute for Research and Development in Microtechnologies\u2014IMT Bucharest, 126A, Erou Iancu Nicolae Street, 077190 Voluntari, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,8,14]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"781","DOI":"10.4143\/crt.2014.261","article-title":"Results of a Phase II Study to Evaluate the Efficacy of Docetaxel and Carboplatin in Metastatic Malignant Melanoma Patients Who Failed First-Line Therapy Containing Dacarbazine","volume":"47","author":"Lee","year":"2015","journal-title":"Cancer Res. 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