Immunotherapy Dosing Strategies: Optimizing Efficacy and Managing Toxicity in Melanoma

Dosing Considerations and Patient Selection

Key Discussion Points:

• Dose-response and dose-toxicity relationships differ between immunotherapy agents
• Clinical scenario-specific treatment selection balancing efficacy needs vs toxicity risks
• Patient characteristics influencing treatment selection for combination immunotherapy

Key Points for Physicians:

• Ipilimumab demonstrates a clear dose-response relationship with higher efficacy but increased toxicity at higher doses (10 mg/kg vs 3mg/kg)
• PD-1 inhibitors do not show similar dose-response relationships, with lower doses demonstrating similar efficacy with less toxicity
• For frail patients with low disease burden, consider PD-1 monotherapy or nivolumab/relatlimab; for patients with high disease burden or brain metastases, ipilimumab/nivolumab may be warranted despite toxicity risks

Notable Insights:

For patients with brain metastases but significant comorbidities or frailty, clinicians may consider nivolumab/relatlimab based on emerging data from studies like Bluebonnet showing intracranial efficacy.

Clinical Significance:

Treatment selection requires careful patient stratification, weighing disease characteristics against patient factors, with dosing decisions that optimize the efficacy-toxicity balance for each individual patient.