NCCN Guidelines® Insights: Melanoma: Cutaneous, Version 2.2024

Featured Updates to the NCCN Guidelines

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Susan M. Swetter Stanford Cancer Institute

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Douglas Johnson Vanderbilt-Ingram Cancer Center

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Mark R. Albertini University of Wisconsin Carbone Cancer Center

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Christopher A. Barker Memorial Sloan Kettering Cancer Center

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Sarah Bateni O’Neal Comprehensive Cancer Center at UAB

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Joel Baumgartner UC San Diego Moores Cancer Center

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Shailender Bhatia Fred Hutchinson Cancer Center

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Christopher Bichakjian University of Michigan Rogel Cancer Center

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Genevieve Boland Mass General Cancer Center

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Sunandana Chandra Robert H. Lurie Comprehensive Cancer Center of Northwestern University

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Bartosz Chmielowski UCLA Jonsson Comprehensive Cancer Center

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Dominick DiMaio Fred & Pamela Buffett Cancer Center

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Roxana Dronca Mayo Clinic Comprehensive Cancer Center

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Ryan C. Fields Siteman Cancer Center at Barnes-Jewish Hospital and Washington University School of Medicine

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Martin D. Fleming The University of Tennessee Health Science Center

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Anjela Galan Yale Cancer Center/Smilow Cancer Hospital

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Samantha Guild AIM at Melanoma

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John Hyngstrom Huntsman Cancer Institute at the University of Utah

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Giorgos Karakousis Abramson Cancer Center at the University of Pennsylvania

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Kari Kendra The Ohio State University Comprehensive Cancer Center - James Cancer Hospital and Solove Research Institute

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Maija Kiuru UC Davis Comprehensive Cancer Center

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Julie R. Lange The Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins

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Ryan Lanning University of Colorado Cancer Center

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Theodore Logan Indiana University Melvin and Bren Simon Comprehensive Cancer Center

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Daniel Olson The UChicago Medicine Comprehensive Cancer Center

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Anthony J. Olszanski Fox Chase Cancer Center

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Patrick A. Ott Dana-Farber/Brigham and Women’s Cancer Center

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Merrick I. Ross The University of Texas MD Anderson Cancer Center

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Luke Rothermel Case Comprehensive Cancer Center/University Hospitals Seidman Cancer Center and Cleveland Clinic Taussig Cancer Institute

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April K. Salama Duke Cancer Institute

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Rohit Sharma UT Southwestern Simmons Comprehensive Cancer Center

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Joseph Skitzki Roswell Park Comprehensive Cancer Center

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Emily Smith University of Michigan Rogel Cancer Center

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Katy Tsai UCSF Helen Diller Family Comprehensive Cancer Center

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Evan Wuthrick Moffitt Cancer Center

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Yan Xing City of Hope National Medical Center

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Nicole McMillian National Comprehensive Cancer Network

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Sara Espinosa National Comprehensive Cancer Network

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The NCCN Guidelines for Cutaneous Melanoma (termed Melanoma: Cutaneous) provide multidisciplinary recommendations for diagnostic workup, staging, and treatment of patients. These NCCN Guidelines Insights focus on the update to neoadjuvant systemic therapy options and summarize the new clinical data evaluated by the NCCN panel for the recommended therapies in Version 2.2024 of the NCCN Guidelines for Cutaneous Melanoma.

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    Kakish H, Pawar O, Bhatty M, et al. Disparities in the receipt of systemic treatment in metastatic melanoma. Am J Clin Oncol 2024;47:239245.

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    Qian Y, Johannet P, Sawyers A, et al. The ongoing racial disparities in melanoma: an analysis of the Surveillance, Epidemiology, and End Results database (1975–2016). J Am Acad Dermatol 2021;84:15851593.

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    Lam M, Zhu JW, Hu A, et al. Racial differences in the prognosis and survival of cutaneous melanoma from 1990 to 2020 in North America: a systematic review and meta-analysis. J Cutan Med Surg 2022;26:181188.

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  • 8.

    Singh SRK, Malapati SJ, Kumar R, et al. NCDB analysis of melanoma 2004–2015: epidemiology and outcomes by subtype, sociodemographic factors impacting clinical presentation, and real-world survival benefit of immunotherapy approval. Cancers (Basel) 2021;13:1455.

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    Whiteman DC, Stickley M, Watt P, et al. Anatomic site, sun exposure, and risk of cutaneous melanoma. J Clin Oncol 2006;24:31723177.

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  • 18.

    Margolin K, Ernstoff MS, Hamid O, et al. Ipilimumab in patients with melanoma and brain metastases: an open-label, phase 2 trial. Lancet Oncol 2012;13:459465.

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    Hodi FS, O’Day SJ, McDermott DF, et al. Improved survival with ipilimumab in patients with metastatic melanoma. N Engl J Med 2010;363:711723.

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    Ascierto PA, Del Vecchio M, Robert C, et al. Ipilimumab 10 mg/kg versus ipilimumab 3 mg/kg in patients with unresectable or metastatic melanoma: a randomised, double-blind, multicentre, phase 3 trial. Lancet Oncol 2017;18:611622.

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  • 21.

    Weber JS, D’Angelo SP, Minor D, et al. Nivolumab versus chemotherapy in patients with advanced melanoma who progressed after anti-CTLA-4 treatment (CheckMate 037): a randomised, controlled, open-label, phase 3 trial. Lancet Oncol 2015;16:375384.

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    Ascierto PA, Ferrucci PF, Fisher R, et al. Dabrafenib, trametinib and pembrolizumab or placebo in BRAF-mutant melanoma. Nat Med 2019;25:941946.

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    Ascierto PA, Long GV, Robert C, et al. Survival outcomes in patients with previously untreated BRAF wild-type advanced melanoma treated with nivolumab therapy: three-year follow-up of a randomized phase 3 trial. JAMA Oncol 2019;5:187194.

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  • 24.

    Kluger HM, Chiang V, Mahajan A, et al. Long-term survival of patients with melanoma with active brain metastases treated with pembrolizumab on a phase II trial. J Clin Oncol 2019;37:5260.

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    Tawbi HA, Schadendorf D, Lipson EJ, et al. Relatlimab and nivolumab versus nivolumab in untreated advanced melanoma. N Engl J Med 2022;386:2434.

  • 26.

    Wolchok JD, Chiarion-Sileni V, Gonzalez R, et al. Long-term outcomes with nivolumab plus ipilimumab or nivolumab alone versus ipilimumab in patients with advanced melanoma. J Clin Oncol 2022;40:127137.

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  • 27.

    Amaria RN, Menzies AM, Burton EM, et al. Neoadjuvant systemic therapy in melanoma: recommendations of the International Neoadjuvant Melanoma Consortium. Lancet Oncol 2019;20:e378389.

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    Patel SP, Othus M, Chen Y, et al. Neoadjuvant-adjuvant or adjuvant-only pembrolizumab in advanced melanoma. N Engl J Med 2023;388:813823.

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    van Akkooi AC, Hieken TJ, Burton EM, et al. Neoadjuvant systemic therapy (NAST) in patients with melanoma: surgical considerations by the International Neoadjuvant Melanoma Consortium (INMC). Ann Surg Oncol 2022;29:36943708.

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  • 31.

    Huang AC, Orlowski RJ, Xu X, et al. A single dose of neoadjuvant PD-1 blockade predicts clinical outcomes in resectable melanoma. Nat Med 2019;25:454461.

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    Sharon CE, Tortorello GN, Ma KL, et al. Long-term outcomes to neoadjuvant pembrolizumab based on pathological response for patients with resectable stage III/IV cutaneous melanoma. Ann Oncol 2023;34:806812.

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  • 33.

    Blank CU, Rozeman EA, Fanchi LF, et al. Neoadjuvant versus adjuvant ipilimumab plus nivolumab in macroscopic stage III melanoma. Nat Med 2018;24:16551661.

  • 34.

    Versluis JM, Menzies AM, Sikorska K, et al. Survival update of neoadjuvant ipilimumab plus nivolumab in macroscopic stage III melanoma in the OpACIN and OpACIN-neo trials. Ann Oncol 2023;34:420430.

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  • 35.

    Rozeman EA, Menzies AM, van Akkooi AC, et al. Identification of the optimal combination dosing schedule of neoadjuvant ipilimumab plus nivolumab in macroscopic stage III melanoma (OpACIN-neo): a multicentre, phase 2, randomised, controlled trial. Lancet Oncol 2019;20:948960.

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  • 36.

    Rozeman EA, Hoefsmit EP, Reijers ILM, et al. Survival and biomarker analyses from the OpACIN-neo and OpACIN neoadjuvant immunotherapy trials in stage III melanoma. Nat Med 2021;27:256263.

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  • 37.

    Blank CU, Reijers ILM, Pennington T, et al. First safety and efficacy results of PRADO: a phase II study of personalized response-driven surgery and adjuvant therapy after neoadjuvant ipilimumab (IPI) and nivolumab (NIVO) in resectable stage III melanoma. J Clin Oncol 2020;38(Suppl):Abstract 10002.

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  • 38.

    Reijers ILM, Rozeman EA, Menzies AM, et al. Continental differences in pathologic response with neoadjuvant ipilimumab (IPI) plus nivolumab (NIVO) in patients with macroscopic stage III melanoma in the phase II OpACIN-neo trial. Ann Oncol 2019;30:Abstract V541.

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  • 39.

    Amaria RN, Reddy SM, Tawbi HA, et al. Neoadjuvant immune checkpoint blockade in high-risk resectable melanoma. Nat Med 2018;24:16491654.

  • 40.

    Amaria RN, Postow M, Burton EM, et al. Neoadjuvant relatlimab and nivolumab in resectable melanoma. Nature 2022;611:155160.

  • 41.

    Amaria RN, Prieto PA, Tetzlaff MT, et al. Neoadjuvant plus adjuvant dabrafenib and trametinib versus standard of care in patients with high-risk, surgically resectable melanoma: a single-centre, open-label, randomised, phase 2 trial. Lancet Oncol 2018;19:181193.

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  • 42.

    Long GV, Saw RP, Lo S, et al. Neoadjuvant dabrafenib combined with trametinib for resectable, stage IIIB-C, BRAFV600 mutation-positive melanoma (NeoCombi): a single-arm, open-label, single-centre, phase 2 trial. Lancet Oncol 2019;20:961971.

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  • 43.

    Dummer R, Gyorki DE, Hyngstrom J, et al. Neoadjuvant talimogene laherparepvec plus surgery versus surgery alone for resectable stage IIIB-IVM1a melanoma: a randomized, open-label, phase 2 trial. Nat Med 2021;27:17891796.

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