Background: High dose interleukin-2 (HD IL-2) can induce durable responses in a subset of patients leading\nto long-term survival. Immune checkpoint blockade (ICB) has demonstrated similarly durable responses in a\nlarger proportion of patients. However, not all patients respond to immune checkpoint blockade and subsequent\ntherapeutic options need to be explored.\nMethods: The PROCLAIM database was queried for patients with metastatic melanoma who had received HD IL-2\nafter treatment with ipilimumab or without prior ICB. Patient characteristics, toxicity and efficacy were analyzed.\nResults: A total of 52 metastatic melanoma patients were treated with high dose IL-2 after ipilimumab and 276\npatients were treated with high dose IL-2 without prior ICB. The overall response rate in the prior ipilimumab\ngroup was 21 % as compared to 12 % in the group that had not received prior ipilimumab. The median overall\nsurvival, measured from the initiation of HD IL-2 therapy, was 19.3 months in the prior ipilimumab group and 19.\n4 months in the no prior ICB group. Toxicities observed on HD IL-2 were relatively equivalent between the\ngroups although there were cases of CTLA4 antibody-induced colitis reported after HD IL-2 treatment and a\nCTLA4 antibody-induced colitis related death.\nConclusion: In this retrospective analysis HD IL-2 therapy displayed antitumor activity in melanoma patients\nwho progressed following treatment with ipilimumab. Most HD IL-2 toxicity was not worsened by prior ipilimumab\ntherapy except for one treatment related death from colitis. Care should be taken to avoid reactivation of CTLA4\nantibody-induced colitis.
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