Balancing Benefits and Toxicity of Immunotherapy in Melanoma

Drs. Peter Forsyth and Muhammad Jaffer, neuro-oncologists at Moffitt Cancer Center, recently co-authored the publication entitled, “A Brain, A Heart, and the Courage: Balancing Benefit and Toxicity of Immunotherapy in Melanoma.”

The overall survival of advanced melanoma has improved dramatically. Immunotherapies, specifically checkpoint inhibitors, have played a large role in this improvement. These agents have also shown benefit in the adjuvant setting, are approved for treatment of resected stage 2, 3 and 4 melanoma, and play an evolving role in the neoadjuvant setting. Although generally well tolerated, immune-related adverse events occur and can be severe.

In the study, they focused on some severe and potentially long-term toxicities, including cardiovascular and neurologic toxicities. The understanding of the acute and long-term toxicities of immune checkpoint inhibitors continues to evolve. Oncologists must continue to balance cancer risk and treatment-related toxicities.

Practical applications:

• Immune checkpoint inhibitors (ICIs) carry potential acute and long-term toxicities.
• Cardiac and neurologic immune-related adverse events can be life-threatening and are important to recognize and manage promptly in consultation with specialists.
• The benefits of ICI therapy must be weighed against the risks, and shared decision-making between the patient and the physician is recommended.

Our understanding of the duration and extent of IrAEs and associated morbidity(ies) continues to advance. To balance the known and unknown risks of ICI and known and unknown benefits, shared decision-making between the treating physician and the patient is recommended. This includes a thorough discussion of potential toxicities, including fatal IrAEs, typical management strategies, and the importance of early reporting and prompt intervention. This may also include a discussion of long-term or delayed IrAEs and of unknown risks, such as the potential increased risk of atherosclerosis and infertility. In advanced unresectable melanoma, OS benefit from ICI is established. In the adjuvant setting, the known benefit of adjuvant PD-1 is recurrence-free survival. For patients with a good prognosis and/or higher risk for IrAEs, long-term or severe IrAEs, it is important to balance these ICI risks with the potential benefits of ICI therapy. This strategy applies to all histologies and treatment scenarios.

Read the full publication.

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