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Marco Donia on managing melanoma brain metastases after progression on anti-PD-1 therapy

Marco Donia/dff.dk

Feb 5, 2025, 20:31

Marco Donia on managing melanoma brain metastases after progression on anti-PD-1 therapy

Marco Donia, Clinical Research Associate Professor at the University of Copenhagen, shared a post on LinkedIn about a recent paper by Sarah E. Lochrin et al. published in JAMA Oncology;

“Limited but not Absent Intracranial Response to Ipilimumab plus Nivolumab in Melanoma Brain Metastases After Progression to Anti-PD-1′

Sarah E. Lochrin et al., January 30, 2025

Managing melanoma brain metastases (MBMs) after progression on anti–PD–1 therapy remains a major challenge. With brain metastases occurring in ~30% of patients with newly diagnosed metastatic melanoma, this retrospective study evaluates the intracranial efficacy of ipilimumab plus nivolumab in the setting of anti-PD-1 resistance

‘Sustained improved survival of patients with metastatic melanoma after the introduction of anti-PD-1-based therapies’

Key Findings (total: 28 patients):

Intracranial Objective Response Rate (ORR): 11% (95% CI, 2%-28%).
Intracranial Progression-Free Survival (PFS): Median 1.6 months (95% CI, 1.2-4.4)
Overall Survival (OS): Median 6.7 months (95% CI, 3.6-10.0)
Extracranial ORR: 14% (95% CI, 4%-33%)

Takeaway: While some patients had intracranial responses, most had rapid disease progression, reinforcing the need for alternative strategies.

Clinical Implications:

Ipilimumab-nivolumab has limited, but not absent, activity in progressive MBM after anti–PD-1 therapy.
Local therapies (e.g., stereotactic radiation) and targeted therapies should be considered when feasible.
Patients with fewer brain metastases and no prior ipilimumab exposure may have better outcomes.

Future Research Needed: Larger and prospective studies are crucial to optimize systemic and combination approaches for PD-1-resistant MBM.

Open questions:

1. Do intracranial responses in PD-1 progressors (12% to 28%, ‘121MO – Anti-IL-8 (BMS-986253) in combination with nivolumab (NIVO) plus ipilimumab (IPI) in patients (pts) with advanced melanoma’ and ‘Ipilimumab with or without nivolumab in PD1/PDL1 blockade refractory metastatic melanoma: a randomized phase 2 trial‘) match those in patients without CNS metastases?

2..How does anti-PD-1 + anti-CTLA-4 compare to targeted therapy for brain metastases?

At CCIT-DK – National Center for Cancer Immune Therapy of Denmark we are actively studying how to approach Brain Metastases on Treatment with high doses of steroids both in vitro/in silico (Marta Sánchez Sánchez and Perrine Verdys, PhD, TIL group) and in a Clinical Trial (PI Troels Holz Borch)

Great work from Michael Postow, James Smithy and others at Memorial Sloan Kettering Cancer Center.”

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Marco Donia on managing melanoma brain metastases after progression on anti-PD-1 therapy