ASO Author Reflections: Tumor Immune Profiling-Based Neoadjuvant Immunotherapy for Locally Advanced Melanoma
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ASO AUTHOR REFLECTIONS
ASO Author Reflections: Tumor Immune Profiling-Based Neoadjuvant Immunotherapy for Locally Advanced Melanoma Kelly M. Mahuron, MD1, Lauren S. Levine, MD2, and Adil I. Daud, MBBS2 1
Department of Surgery, University of California, San Francisco, CA; 2Department of Medicine, University of California, San Francisco, CA
PAST During the past decade, immunotherapy and checkpoint blockade have revolutionized the treatment of metastatic melanoma. The demonstrated benefit of adjuvant immunotherapy for locally advanced melanoma encouraged the development of clinical trials to assess the role of neoadjuvant immunotherapy in this patient population.1 Two prospective trials have supported the feasibility of neoadjuvant checkpoint blockade for resectable Stage III melanoma.2,3 Both studies reported high rates of objective response to combination therapy with anti-PD-1 and CLTA-4 inhibitors, but a substantial proportion of these patients experienced significant immune-related adverse events (irAEs) that limited the tolerability and duration of their therapy. These studies also reported low response rates with single agent PD-1 blockade (in unselected patients). This study examined the efficacy of neoadjuvant immunotherapy and whether treatment stratification guided by immune profiling can enhance treatment results and avoid unnecessary toxicity. PRESENT Our group has previously demonstrated that the percentage of T cells within the tumor microenvironment expressing exhaustion markers can predict response to antiPD-1 monotherapy in the metastatic setting, and that tumors with low fraction of exhausted T cells may still
Ó Society of Surgical Oncology 2020 First Received: 15 May 2020 A. I. Daud, MBBS e-mail: [email protected]
respond to combination CTLA-4/PD-1 blockade.4,5 Immune profiling therefore can be used to stratify therapy groups; patients with favorable profiles can receive antiPD-1 monotherapy and avoid the toxicities of anti-CTLA-4 agents, whereas patients unlikely to respond to monotherapy receive combination immunotherapy. This study applied this immune profiling-based stratification to 17 patients with resectable stage III or oligometastatic stage IV melanoma.6 Ten patients received anti-PD-1 monotherapy, and seven received anti-CTLA-4/PD-1 combination therapy. Sixteen patients (94%) achieved either a complete or partial response, and 8 of the 11 patients who underwent subsequent surgical resection attained a complete pathologic response. Only three (17.6%) patients experienced clinically severe (grade 3 or 4) irAEs. FUTURE In alignment with other studies of neoadjuvant immunotherapy in locally advanced melanoma, this study demonstrated a high rate of objective response, relapse-free survival, and overall survival. Of note, five patients declined surgery after achieving a complete radiographic response, and all remain disease-free at a median follow-up of 27.6 months. In contrast to previous neoadjuvant studies, which reported high rates of irAEs, neoadjuvant immunotherapy was well tolerate
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