IMUN-08 DURABLE RESPONSE TO IPILIMUMAB-NIVOLUMAB (IPI-NIVO) IN ANTI-PD1 REFRACTORY MERKEL CELL CARCINOMA WITH LEPTOMENINGEAL DISEASE PROGRESSION Open Access

Leptomeningeal disease (LMD) is a rare complication of Merkel cell carcinoma (MCC), which has been described in limited case reports, none of which describe outcomes with IPI-NIVO. Here we describe a patient with PD-1 refractory MCC LMD with durable response to IPI-NIVO. A 69-year-old male diagnosed with stage IIIA MCC underwent left groin dissection and radiation. He developed recurrence in distant lymph nodes and started pembrolizumab (PEMBRO). Seven months after starting PEMBRO, he developed lower extremity weakness. Spine MRI showed LMD involving cauda equina. CSF testing detected tumor cells. Imaging did not show any recurrence aside from LMD. He received radiation to L1-S2 followed by IPI-NIVO. His LMD has remained clinically and radiographically stable 10 months after starting IPI-NIVO. Longitudinal circulating tumor DNA (ctDNA) monitoring demonstrated clearance both after starting PEMBRO and IPI-NIVO. ctDNA was detectable 5 weeks after starting PEMBRO and 5 months after starting IPI-NIVO and became undetectable 10 weeks after starting PEMBRO and again 8 months after starting IPI-NIVO. We prospectively collected peripheral blood at baseline prior to PEMBRO, when LMD developed, with cycle 3 IPI-NIVO, when he developed pneumonitis 4 months from cycle 1, and following CNS and systemic tumor clearance at 7 months from cycle 1 of IPI-NIVO with patient on maintenance NIVO alone. Peripheral flow cytometry, quantitative proteomics, and serum cytokines were used to characterize immune cell numbers and phenotypes in this exceptional responder. Kinetics of immune correlates, including CD33+HLADRlo, CD15+CD14-MDSC, CD57+ CD8+ T cells, showed distinctive changes during the clinical course. This case demonstrates unique response to IPI-NIVO with durable neurologic stability and confirmatory ctDNA clearance in a patient with PD-1 refractory MCC and less common CNS progression with documented LMD. Although the prognosis of MCC LMD is poor, this patient achieved an objective CNS response, and we reversed PD-1 resistance with IPI-NIVO.