Response to anti-PD1/PDL1 therapy in patients with metastatic desmoplastic melanoma.

9011 Background: Higher overall burden of somatic mutations in tumors may be associated with better response rates to immunotherapy. Desmoplastic melanoma (DM) is a rare subtype of melanoma comprising approximately 1% of cases. Since DM has been reported to have a higher mutational load than other sub-types of melanoma, we hypothesized that patients with metastatic DM may respond more frequently to anti-PD1 or anti-PDL1 immunotherapies. Methods: A retrospective analysis of over 1000 melanoma patients treated with anti-PD1/PDL1 therapies among seven institutions (UCLA, MD Anderson, UCSF, Memorial Sloan Kettering, Vanderbilt, Melanoma Institute Australia, and Westmead) was conducted to identify patients with DM. We assessed objective response rates (ORR), overall survival (OS), and progression-free survival (PFS). Results: We identified 23 patients with stage IV DM (either pure or mixed subtype), 2 with stage M1a, 11 with M1b, and 10 with M1c disease. Eighteen patients had received prior systemic therapy, including 12 whose disease progressed following ipilimumab. Three patients were treated with nivolumab (anti-PD1 antibody, doses 0.1 or 3 mg/kg), 1 with nivolumab (3mg/kg) plus ipilimumab (1 mg/kg), 3 with BMS-936559 (anti-PDL1, 0.1 or 0.3 mg/kg), and 16 with pembrolizumab (anti-PD1, 2 or 10 mg/kg). Patients received a median of 9 cycles of therapy. A RECIST ORR of 70% was observed, including 9 complete responses and 7 partial responses (3 with > 75% decrease in tumor size per RECIST criteria). Median length of follow-up was 13.4 months. Three patients with eventual isolated progression underwent surgical excision without further disease progression, and only 2 of 23 patients received subsequent systemic therapy. Eighteen patients were alive at last follow-up; Kaplan-Meier median OS (range 2.8 months to 3.5+ years) and median PFS (range 1.4 months to 2.7+ years) were not reached. Conclusions: Patients with metastatic DM appear to have higher response rates and favorable clinical outcomes to anti-PD/PDL1 therapy compared to other patients with advanced melanoma. Additional mechanistic studies are ongoing.