Neoadjuvant checkpoint inhibitor immunotherapy for resectable mucosal melanoma

Joel Ho, Jane Mattei, Michael Tetzlaff, Michelle D. Williams, Michael A. Davies, Adi Diab, Isabella C.Glitza Oliva, Jennifer McQuade, Sapna P. Patel, Hussein Tawbi, Michael K. Wong, Sarah B. Fisher, Ehab Hanna, Emily Z. Keung, Merrick Ross, Roi Weiser, Shirley Y. Su, Michael Frumovitz, Larissa A. Meyer, Amir JazaeriCurtis A. Pettaway, B. Ashleigh Guadagnolo, Andrew J. Bishop, Devarati Mitra, Ahsan Farooqi, Roland Bassett, Silvana Faria, Priyadharsini Nagarajan, Rodabe N. Amaria

Research output: Contribution to journalArticlepeer-review

16 Scopus citations

Abstract

Background: Neoadjuvant checkpoint inhibition (CPI) has recently demonstrated impressive outcomes in patients with stage 3 cutaneous melanoma. However, the safety, efficacy, and outcome of neoadjuvant CPI in patients with mucosal melanoma (MM) are not well studied as MM is a rare melanoma subtype. CPI such as combination nivolumab and ipilimumab achieves response rates of 37-43% in unresectable or metastatic MM but there is limited data regarding the efficacy of these agents in the preoperative setting. We hypothesize that neoadjuvant CPI is a safe and feasible approach for patients with resectable MM. Method: Under an institutionally approved protocol, we identified adult MM patients with resectable disease who received neoadjuvant anti-PD1 +/- anti-CTLA4 between 2015 to 2019 at our institution. Clinical information include age, gender, presence of nodal involvement or satellitosis, functional status, pre-treatment LDH, tumor mutation status, and treatment data was collected. Outcomes include event free survival (EFS), overall survival (OS), objective response rate (ORR), pathologic response rate (PRR), and grade ≥3 toxicities. Results: We identified 36 patients. Median age was 62; 58% were female. Seventy-eight percent of patients received anti-PD1 + anti-CTLA4. Node positive disease or satellite lesions was present at the time of treatment initiation in 47% of patients. Primary sites of disease were anorectal (53%), urogenital (25%), head and neck (17%), and esophageal (6%). A minority of patients did not undergo surgery due to complete response (n=3, 8%) and disease progression (n=6, 17%), respectively. With a median follow up of 37.9 months, the median EFS was 9.2 months with 3-year EFS rate of 29%. Median OS had not been reached and 3-year OS rate was 55%. ORR was 47% and PRR was 35%. EFS was significantly higher for patients with objective response and for patients with pathologic response. OS was significantly higher for patients with pathologic response. Grade 3 toxicities were reported in 39% of patients. Conclusion: Neoadjuvant CPI for resectable MM is a feasible approach with signs of efficacy and an acceptable safety profile. As there is currently no standard approach for resectable MM, this study supports further investigations using neoadjuvant therapy for these patients.

Original languageEnglish (US)
Article number1001150
JournalFrontiers in Oncology
Volume12
DOIs
StatePublished - Oct 17 2022
Externally publishedYes

Keywords

  • immunotherapy
  • melanoma
  • mucosal melanoma
  • neoadjuvant
  • resectable

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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