Tumor Immune Profiling-Based Neoadjuvant Immunotherapy for Locally Advanced Melanoma
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ORIGINAL ARTICLE – MELANOMA
Tumor Immune Profiling-Based Neoadjuvant Immunotherapy for Locally Advanced Melanoma Lauren S. Levine, MD1, Kelly M. Mahuron, MD2, Katy K. Tsai, MD1, Clinton Wu, BS1, Daiva M. Mattis, MD, PhD3, Mariela L. Pauli, MS4, Arielle Oglesby, BS1, James C. Lee, MD1, Matthew H. Spitzer, PhD5, Matthew F. Krummel, PhD3, Alain P. Algazi, MD1, Michael D. Rosenblum, MD, PhD4, Michael Alvarado, MD2, and Adil I. Daud, MBBS1 1
Department of Medicine, Helen Diller Family Comprehensive Cancer Center, University of California, San Francisco, San Francisco, CA; 2Department of Surgery, Helen Diller Family Comprehensive Cancer Center, University of California, San Francisco, San Francisco, CA; 3Department of Pathology, Helen Diller Family Comprehensive Cancer Center, University of California, San Francisco, San Francisco, CA; 4Department of Dermatology, Helen Diller Family Comprehensive Cancer Center, University of California, San Francisco, San Francisco, CA; 5Department of Otolaryngology, Helen Diller Family Comprehensive Cancer Center, University of California, San Francisco, San Francisco, CA
ABSTRACT Background. The frequency of ‘‘exhausted’’ or checkpoint-positive (PD-1?CTLA-4?) cytotoxic lymphocytes (Tex) in the tumor microenvironment is associated with response to anti-PD-1 therapy in metastatic melanoma. The current study determined whether pretreatment Tex cells in locally advanced melanoma predicted response to neoadjuvant anti-PD-1 blockade. Methods. Pretreatment tumor samples from 17 patients with locally advanced melanoma underwent flow cytometric analysis of pretreatment Tex and regulatory T cell frequency. Patients who met the criteria for neoadjuvant checkpoint blockade were treated with either PD-1 monotherapy or PD-1/CTLA-4 combination therapy. Best overall response was evaluated by response evaluation criteria in solid tumors version 1.1, with recurrence-free survival (RFS) calculated by the Kaplan–Meier test. The incidence and severity of adverse events were tabulated by
Electronic supplementary material The online version of this article (https://doi.org/10.1245/s10434-020-08648-7) contains supplementary material, which is available to authorized users. Ó Society of Surgical Oncology 2020 First Received: 23 February 2020 A. I. Daud, MBBS e-mail: [email protected]
clinicians using the National Cancer Institute Common Terminology Criteria for Adverse Events version 4. Results. Of the neoadjuvant treated patients, 10 received anti-PD-1 monotherapy and 7 received anti-CTLA-4/PD-1 combination therapy. Of these 17 patients, 12 achieved a complete response, 4 achieved partial responses, and 1 exhibited stable disease. Surgery was subsequently performed for 11 of the 17 patients, and 8 attained a complete pathologic response. Median RFS and overall survival (OS) were not reached. Immune-related adverse events comprised four grade 3 or 4 events, including pneumonitis, transaminitis, and anaphylaxis. Conclusion. The results showed high rates of objective response, RFS, and OS for patients unde
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