Outcomes of neoadjuvant immunotherapy (NeoIO) in Merkel cell carcinoma.

9589 Background: Merkel cell carcinoma (MCC) is an aggressive malignancy with high rate of nodal and distant metastasis, leading to poor overall survival. For clinically detected regional lymph nodes, treatment typically involves node dissection with adjuvant radiotherapy. Evaluation of NeoIO in resectable MCC resulted in a pathological complete response (pCR) rate of 47%; pCR correlated with relapse-free survival (RFS). However, there is no standardized NeoIO regimen. We report our single institutional NeoIO experience in resectable MCC and correlate regimen with clinicopathological response. Methods: We retrospectively reviewed pts with resectable MCC who received NeoIO with intent to offer surgery (SX) or radiation (RT), from 2015 to present. Demographic and clinicopathological characteristics were evaluated. Overall Response Rate (ORR), pCR, and Relapse Free Survival (RFS) were computed. Overall survival (OS) was evaluated via a 90-day landmark Kaplan-Meier plot to assess if time to definitive regional treatment impacted OS. Results: We identified 25 patients; median age was 77 years old; 75% were male. Majority were clinical stage III (IIIa 20%; IIIb 68%); 12% were stage IIa. 32% had immunosuppression at the time of treatment. 36% had primary MCC on extremity, 36% on head and neck, 8% on trunk, and 20% were of unknown primary origin. 80% of patients received neoadjuvant Pembrolizumab, 16% Avelumab and 4% ipilimumab plus nivolumab. The median number of IO cycles was 3 (1-18); those who completed 1-2 cycles were more likely to receive SX/RT compared to those who received 3 or more cycles (p-value = 0.024). 64% of patients had an adverse effect during therapy; majority (87.5%) had G1/G2 events. 24 patients had post NeoIO imaging to which ORR was 75%. Post NeoIO, 15 underwent SX, 4 had definitive RT, 2 had progression of disease and received systemic therapy, 3 had comorbidities precluding treatment, and 1 was lost to follow up. The median time from beginning of NeoIO to SX or RT was 3 months (1-19mo). Of those who underwent SX, 40% had a complete pathologic response, 20% had a major pathologic response, 33% had a partial response, and 6% had non-response. With a median 23.4 months of follow-up, 8 of the 25 patients (32%) have experienced an event and the median EFS has not been reached. 7 of the 25 (28%) patients have died, 4 due to MCC; median overall survival not reached. Median follow up was 23.4 months. Time to event analysis indicated six patients who received NeoIO, followed with SX or RT within 90 days, had fewer deaths compared with those who received SX/RT after 90 days. Survival was approximately 3.5 years for those who did not receive SX/RT within 90 days and no deaths for those who received SX/RT within 90 days. Conclusions: NeoIO for MCC at our single institution achieved an ORR of 75% and a mPR/pCR of 60%. Earlier incorporation of regional therapy post NeoIO appears to improve outcomes, suggesting importance of multimodal management for resectable MCC.