Characterization of patients with metastatic melanoma that relapses following complete metabolic response from anti–PD-1 therapy.

Abstract

9530 Background: Treatment with PD-1 inhibitor-based therapy has significantly improved survival in patients with metastatic melanoma over the past decade. Many of these patients achieve complete metabolic response (CMR) by FDG-PET/CT and electively stop treatment. However, the outcomes of patients who relapse after CMR remain uncertain. In this study, we attempt to further characterize metastatic melanoma patients who relapsed following elective discontinuation of anti-PD-1 based therapy due to CMR. Methods: We performed a single-center, retrospective analysis on a cohort of patients with metastatic or unresectable melanoma from 2012 to 2021 who were treated with anti-PD-1 monotherapy (pembrolizumab or nivolumab) or combination ipilimumab/nivolumab (I/N), with or without local therapies (surgery or radiation therapy). Patients who achieved a CMR from treatment were identified. CMR was defined as no evidence of metabolically active disease on full-body 18F-FDG-PET/CT and no evidence of new intracranial metastasis on MRI brain. Multiple clinical variables and survival outcomes were assessed. Results: Among 386 advanced stage melanoma patients analyzed, 87 achieved a CMR followed by elective treatment cessation with a median anti-PD-1 therapy duration of 10.4 months. 19/87 patients had brain metastasis at baseline. 17/87 patients had disease relapse with a median time to relapse from CMR of 12.1 months. Of those 17 patients, 8 received I/N, 9 received anti-PD-1 monotherapy, and 2 required local therapies to obtain CMR. 7/17 patients were able to achieve CMR again following resumption of anti-PD-1 monotherapy (n = 6) and BRAF/MEK targeted therapy (n = 1). 10/17 patients relapsed in the brain with 7 of those patients having no history of brain metastasis at baseline. Median overall survival after relapse from CMR was 34.1 months. The most common cause of death following relapse from CMR was brain metastasis progression (n = 5). Conclusions: A small proportion of metastatic melanoma patients who achieve complete metabolic (CMR) following treatment with anti-PD-1 therapy develop disease relapse. We found that relapse in the brain is common, regardless of baseline involvement at time of therapy, and is a common cause of mortality suggesting the importance of intracranial surveillance following treatment cessation. Ongoing studies are warranted to identify clinicopathologic factors that predict relapse to better inform patients and providers who elect to stop anti-PD-1 therapy.