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

## TL;DR

This paper reports rare but severe blood-related side effects in skin cancer patients treated with immune checkpoint inhibitors, highlighting the need for better awareness and monitoring.

## Contribution

The study presents a case series of hematologic immune-related adverse events in skin cancer patients treated with ICIs, emphasizing clinical features and potential warning signs.

## Key findings

- Hemolytic anemia was the most frequent hematologic toxicity observed in the cases.
- Hematologic events occurred regardless of the patient's response to ICI treatment.
- Previous gastrointestinal or systemic symptoms and elevated lactate dehydrogenase levels may serve as warning signs for hematologic irAEs.

## Abstract

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.

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.

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.