Background: PD-1/PD-L1 inhibitors (aPD-1) have demonstrated efficacy in the treatment of metastatic melanoma (MM) and advanced renal cell carcinoma (RCC). HD IL-2 can produce durable responses in a subset of patients and remains a treatment option. As aPD-1 therapy becomes the backbone of mm and RCC treatment it becomes increasingly important to understand whether HD IL-2 is safe and effective following immune checkpoint blockade (ICB). Methods: PROCLAIM^SM (www.proclaimregistry.com, NCT01415167) is an IL-2 observational registry with > 40 participating sites consisting of a retrospective (n = 370, locked) and prospective cohort (n > 942, on-going). We queried the prospective cohort to identify pts treated with HD IL-2 after aPD-1 and report their safety and efficacy outcomes, compared to pts who had not received any ICB prior to HD IL-2. Results: Within the database, there are currently 16 patients who received aPD-1 prior to HD IL-2 therapy, 12 patients (3 RCC and 9 MM) had sufficient data as of 12/17/2015 to analyze outcome. Of these 12 patients, seven with mm also received ipilimumab and 3 with RCC also received anti-VEGF therapy prior to treatment with HD IL-2. The most common and reversible toxicities reported as the reason(s) to stop dosing for Cycle 1 in the patients who had previously been treated with aPD-1 were hypotension, diarrhea, vomiting, hypoxia, renal failure and arrhythmia. These toxicities were similar to those observed among the 681 HD IL-2 patients without prior ICB. There were no IL-2 related deaths noted in the cohort receiving prior aPD-1. The one year overall survival from HD IL-2 was 76% in patients who previously received aPD-1 versus 74% in patients who had not previously been treated with ICB. The ORR was 8.3% in patients with prior aPD-1 vs. 15% in those without prior ICB. Conclusions: Data from the PROCLAIM database suggests that HD IL-2 remains a treatment option for pts who have had progressive disease after prior PD-1 inhibition. Continued analysis of patients treated with HD IL-2 will help guide the optimal sequence of these immunotherapies.