Retreatment of Patients with Metastatic Cutaneous Melanoma Who Relapse after Elective Checkpoint Inhibitor Discontinuation after a Complete Remission

Abstract

Introduction: Checkpoint blockade has improved the response rate and survival in metastatic melanoma. Elective treatment discontinuation appears to be reasonable in most patients who have achieved a confirmed complete remission. It seems crucial to understand whether restarting immune checkpoint inhibitor therapy can induce additional responses or remissions in rare patients who relapse. Methods: A retrospective analysis identified only 10 patients who relapsed after elective treatment discontinuation after a radiologically confirmed remission. These patients were retreated with single-agent PD-1 or combined CTLA-4 plus PD-1-directed monoclonal antibodies. Results: We found an initial complete response rate of 20% (2 patients) following retreatment. With a median follow-up of 26 months, the addition of individualized salvage therapies converted an additional 4 patients to a 2nd remission. All 6 of these patients have again discontinued therapy. Three patients have died of metastatic melanoma, while another is receiving salvage therapy. Six of our 10 patients experienced grades 2-3 retreatment-related toxicity. There were no hospitalizations or fatalities. Discussion: Retreatment of relapsing patients resulted in 20% complete responses with checkpoint inhibitors. The planned addition of other treatment modalities converted another 4 patients (40%) to a durable 2nd remission. This sequential approach merits further exploration in prospective clinical trials.