Melanoma is an aggressive skin cancer with historically limited treatment options. Approximately 50% of melanomas harbor BRAF V600 mutations. This report describes a 32-year-old man with metastatic BRAF V600-mutant melanoma who presented with cardiac involvement. Recently developed treatment options for patients with BRAF-mutant melanoma include BRAF inhibitors (vemurafenib, dabrafenib), MEK inhibitors (trametinib), and immune-based therapeutics (interleukin-2 or ipilimumab), but the most effective strategy for first-line therapy is heavily debated. Opinions vary for treatment selection, but the general consensus recommends immune-based therapies initially for asymptomatic patients with low-volume disease, and BRAF inhibitors for those with highly symptomatic or rapidly progressing disease. In this case, melanoma with cardiac involvement, although clinically uncommon, presents challenging management decisions.
Douglas B. Johnson and Jeffrey A. Sosman
Presenters: Douglas B. Johnson, Susan M. Swetter, April K.S. Salama, and Evan Wuthrick
Several advances in diagnosis and treatment of cutaneous melanoma were discussed at the NCCN 2021 Virtual Annual Conference. First, advances in immunotherapies and targeted agents have enhanced the role of systemic therapies in the up-front management of brain metastases in melanoma while improving survival. With dual-agent immune checkpoint inhibitors, more than half of patients with asymptomatic brain metastases that are not in high-risk anatomic areas of the brain respond to treatment, and these responses appear to be durable, sparing many patients from neurosurgery and/or stereotactic radiosurgery. In addition, molecular tests increasingly have implications for clinical decision-making in later-stage disease. The most important genetic mutation in melanoma is the BRAF V600 mutation, which can be found in approximately 40% to 50% of cutaneous melanomas.
Douglas B. Johnson, Riyue Bao, Kristin K. Ancell, Anthony B. Daniels, Deborah Wallace, Jeffrey A. Sosman, and Jason J. Luke
Background: Uveal melanoma (UM) is an uncommon melanoma subtype with poor prognosis. Agents that have transformed the management of cutaneous melanoma have made minimal inroads in UM. Methods: We conducted a single-arm phase II study of pembrolizumab in patients with metastatic UM and performed bioinformatics analyses of publicly available datasets to characterize the activity of anti–PD-1 in this setting and to understand the mutational and immunologic profile of this disease. Results: A total of 5 patients received pembrolizumab in this study. Median overall survival was not reached, and median progression-free survival was 11.0 months. One patient experienced a complete response after one dose and 2 others experienced prolonged stable disease (20% response rate, 60% clinical benefit rate); 2 additional patients had rapidly progressing disease. Notably, the patients who benefited had either no liver metastases or small-volume disease, whereas patients with rapidly progressing disease had bulky liver involvement. We performed a bioinformatics analysis of The Cancer Genome Atlas for UM and confirmed a low mutation burden and low rates of T-cell inflammation. Note that the lack of T-cell inflammation strongly correlated with MYC pathway overexpression. Conclusions: Anti–PD-1–based therapy may cause clinical benefit in metastatic UM, seemingly more often in patients without bulky liver metastases. Lack of mutation burden and T-cell infiltration and MYC overexpression may be factors limiting therapeutic responses.
ClinicalTrials.gov identifier: NCT02359851
Featured Updates to the NCCN Guidelines
Susan M. Swetter, John A. Thompson, Mark R. Albertini, Christopher A. Barker, Joel Baumgartner, Genevieve Boland, Bartosz Chmielowski, Dominick DiMaio, Alison Durham, Ryan C. Fields, Martin D. Fleming, Anjela Galan, Brian Gastman, Kenneth Grossmann, Samantha Guild, Ashley Holder, Douglas Johnson, Richard W. Joseph, Giorgos Karakousis, Kari Kendra, Julie R. Lange, Ryan Lanning, Kim Margolin, Anthony J. Olszanski, Patrick A. Ott, Merrick I. Ross, April K. Salama, Rohit Sharma, Joseph Skitzki, Jeffrey Sosman, Evan Wuthrick, Nicole R. McMillian, and Anita M. Engh
Over the past few years, the NCCN Guidelines for Melanoma: Cutaneous have been expanded to include pathways for treatment of microscopic satellitosis (added in v2.2020), and the following Principles sections: Molecular Testing (added in v2.2019), Systemic Therapy Considerations (added in v2.2020), and Brain Metastases Management (added in v3.2020). The v1.2021 update included additional modifications of these sections and notable revisions to Principles of: Pathology, Surgical Margins for Wide Excision of Primary Melanoma, Sentinel Lymph Node Biopsy, Completion/Therapeutic Lymph Node Dissection, and Radiation Therapy. These NCCN Guidelines Insights discuss the important changes to pathology and surgery recommendations, as well as additions to systemic therapy options for patients with advanced disease.
Featured Updates to the NCCN Guidelines
Shaji K. Kumar, Natalie S. Callander, Jens Hillengass, Michaela Liedtke, Muhamed Baljevic, Erica Campagnaro, Jorge J. Castillo, Jason C. Chandler, Robert F. Cornell, Caitlin Costello, Yvonne Efebera, Matthew Faiman, Alfred Garfall, Kelly Godby, Leona Holmberg, Myo Htut, Carol Ann Huff, Yubin Kang, Ola Landgren, Ehsan Malek, Thomas Martin, James Omel, Noopur Raje, Douglas Sborov, Seema Singhal, Keith Stockerl-Goldstein, Carlyn Tan, Donna Weber, Alyse Johnson-Chilla, Jennifer Keller, and Rashmi Kumar
The NCCN Guidelines for Multiple Myeloma provide recommendations for diagnosis, workup, treatment, follow-up, and supportive care for patients with monoclonal gammopathy of renal significance, solitary plasmacytoma, smoldering myeloma, and multiple myeloma. These NCCN Guidelines Insights highlight some of the important updates and changes in the 1.2020 version of the NCCN Guidelines for Multiple Myeloma.
Daniel G. Coit, John A. Thompson, Mark R. Albertini, Christopher Barker, William E. Carson III, Carlo Contreras, Gregory A. Daniels, Dominick DiMaio, Ryan C. Fields, Martin D. Fleming, Morganna Freeman, Anjela Galan, Brian Gastman, Valerie Guild, Douglas Johnson, Richard W. Joseph, Julie R. Lange, Sameer Nath, Anthony J. Olszanski, Patrick Ott, Aparna Priyanath Gupta, Merrick I. Ross, April K. Salama, Joseph Skitzki, Jeffrey Sosman, Susan M. Swetter, Kenneth K. Tanabe, Evan Wuthrick, Nicole R. McMillian, and Anita M. Engh
The NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines) for Cutaneous melanoma have been significantly revised over the past few years in response to emerging data on immune checkpoint inhibitor therapies and BRAF-targeted therapy. This article summarizes the data and rationale supporting extensive changes to the recommendations for systemic therapy as adjuvant treatment of resected disease and as treatment of unresectable or distant metastatic disease.
Daniel G. Coit, John A. Thompson, Alain Algazi, Robert Andtbacka, Christopher K. Bichakjian, William E. Carson III, Gregory A. Daniels, Dominick DiMaio, Ryan C. Fields, Martin D. Fleming, Brian Gastman, Rene Gonzalez, Valerie Guild, Douglas Johnson, Richard W. Joseph, Julie R. Lange, Mary C. Martini, Miguel A. Materin, Anthony J. Olszanski, Patrick Ott, Aparna Priyanath Gupta, Merrick I. Ross, April K. Salama, Joseph Skitzki, Susan M. Swetter, Kenneth K. Tanabe, Javier F. Torres-Roca, Vijay Trisal, Marshall M. Urist, Nicole McMillian, and Anita Engh
The NCCN Guidelines for Melanoma have been significantly revised over the past few years in response to emerging data on a number of novel agents and treatment regimens. These NCCN Guidelines Insights summarize the data and rationale supporting extensive changes to the recommendations for systemic therapy in patients with metastatic or unresectable melanoma.
David S. Ettinger, Wallace Akerley, Gerold Bepler, Matthew G. Blum, Andrew Chang, Richard T. Cheney, Lucian R. Chirieac, Thomas A. D'Amico, Todd L. Demmy, Ramaswamy Govindan, Frederic W. Grannis Jr., Thierry Jahan, David H. Johnson, Anne Kessinger, Ritsuko Komaki, Feng-Ming Kong, Mark G. Kris, Lee M. Krug, Quynh-Thu Le, Inga T. Lennes, Renato Martins, Janis O'Malley, Raymond U. Osarogiagbon, Gregory A. Otterson, Jyoti D. Patel, Katherine M. Pisters, Karen Reckamp, Gregory J. Riely, Eric Rohren, Scott J. Swanson, Douglas E. Wood, and Stephen C. Yang
Featured Updates to the NCCN Guidelines
P. Kumar Rao, Christopher Barker, Daniel G. Coit, Richard W. Joseph, Miguel Materin, Ramesh Rengan, Jeffrey Sosman, John A. Thompson, Mark R. Albertini, Genevieve Boland, William E. Carson III, Carlo Contreras, Gregory A. Daniels, Dominick DiMaio, Alison Durham, Ryan C. Fields, Martin D. Fleming, Anjela Galan, Brian Gastman, Kenneth Grossman, Valerie Guild, Douglas Johnson, Giorgos Karakousis, Julie R. Lange, ScM, Kim Margolin, Sameer Nath, Anthony J. Olszanski, Patrick A. Ott, Merrick I. Ross, April K. Salama, Joseph Skitzki, Susan M. Swetter, Evan Wuthrick, Nicole R. McMillian, and Anita Engh
The NCCN Guidelines for Uveal Melanoma include recommendations for staging, treatment, and follow-up of patients diagnosed with uveal melanoma of the choroid or ciliary body. In addition, because distinguishing between uveal melanoma and benign uveal nevi is in some cases difficult, these guidelines also contain recommendations for workup of patients with suspicious pigmented uveal lesions, to clarify the tests needed to distinguish between those who should have further workup and treatment for uveal melanoma versus those with uncertain diagnosis and low risk who should to be followed and later reevaluated. These NCCN Guidelines Insights describe recommendations for treatment of newly diagnosed nonmetastatic uveal melanoma in patients who have already undergone a complete workup.