Tebentafusp in Metastatic Uveal Melanoma: A Case Series and Practical Guidance for Toxicity Management

Abstract

Uveal melanoma (UM) is a rare malignancy with poor outcomes in the metastatic setting and limited benefit from conventional systemic therapies. Tebentafusp, a novel bispecific fusion protein targeting glycoprotein 100 (gp100) in human leukocyte antigen A (HLA-A)*02:01–positive patients, has recently demonstrated a survival advantage, being approved in Brazil in 2025. However, its distinct toxicity profile, particularly cytokine-release syndrome, rash, and liver enzyme elevations, remain unfamiliar to many clinicians. Reporting early real-world experiences can provide valuable practical guidance for managing these adverse events in routine practice.

In this case series, we describe four adult HLA-A*02:01–positive patients with metastatic UM treated with tebentafusp at a single Brazilian center. All participants initiated therapy in an inpatient setting following standardized institutional routines designed for safe administration, including structured premedication, continuous monitoring, and predefined response algorithms for early infusion reactions. Across cases, predictable early reactions were successfully managed using protocol-based interventions—such as antihistamines, low-dose corticosteroids, intravenous fluids, and targeted supportive care—allowing uninterrupted dose escalation and subsequent transition to outpatient treatment. These cases illustrate the practical steps, decision pathways, and monitoring strategies that enable safe implementation of tebentafusp in real-world practice.

This case series highlights the characteristic toxicities associated with tebentafusp and emphasizes the importance of early recognition and proactive management strategies to ensure treatment continuation. Our experience provides pragmatic insights that may support oncologists in Brazil as they begin to integrate tebentafusp into the care of patients with metastatic UM.