Hematologic immune-related adverse events in skin cancer patients treated with immune checkpoint inhibitors: a case series

Rosa Falcone¹Alessandra Frezzolini²Emanuele Bruni^3*Sofia Verkhovskaia¹Maria Luigia Carbone⁴Francesca Romana Di Pietro¹Paolo Chesi¹Gabriele Piesco¹Maria Cantonetti¹Paolo Marchetti¹Federica De Galitiis¹Cristina M Failla⁵

• ¹Department of Oncology and Dermato-oncology, IDI-IRCCS, Rome, Italy
• ²Laboratory of Immunology and Allergology, IDI-IRCCS, Rome, Italy
• ³Departmental Faculty of Medicine and Surgery, UniCamillus-Saint Camillus International University of Health Sciences, Rome, Italy
• ⁴Clinical Trial Center, IDI-IRCCS, Rome, Italy
• ⁵Experimental Immunology Laboratory, IDI-IRCCS, Rome, Italy

Background: Immune checkpoint inhibitors (ICIs) are the gold standard therapy for cutaneous melanoma and are also used effectively in treating other types of skin cancer. Hematologic toxicities are rare, but potentially a serious and life-threatening side effect of ICIs. Clinical and biological biomarkers able to predict these events have been poorly explored and have not yet been identified. Case presentation: We present four cases of hematologic toxicity in melanoma patients and one case in a patient with cutaneous squamous cell carcinoma, all of which arose during treatment with ICIs in an adjuvant or metastatic setting. Hemolytic anemia was the most frequent event; neutropenia with agranulocytosis happened in one case and was fatal. ICI treatment was discontinued in all five cases and was never restarted. Two prevalent features were male sex and older age (>70 years old). These events were independent of the response to ICIs. Indeed, they occurred in a patient who progressed during treatment and in patients who responded completely to therapy. Previous diarrhea due to ICIs (patients 1, 2, and 5), asthenia (patients 3 and 4), and a sudden increase in lactate dehydrogenase levels despite the absence of disease progression (patients 2, 3, 4, and 5) might be warning signs of subsequent hematologic irAEs. Conclusion: Our study underscores the rarity and potential severity of hematologic toxicities, underlining the need for heightened clinician awareness and the incorporation of hematologic guidance into oncologic practice. Although predictive biomarkers remain unvalidated, monitoring immune cell subsets or recognizing warning signals early on may facilitate diagnosis and improve prognosis.