Summary of the 19th Annual MCC Multi-Center Interest Group (MMIG)

Summary of 19th Annual MMIG Meeting 

(Merkel cell carcinoma Multi-Center Interest Group) 

Friday, March 7th, 2025 

Orlando, FL & Virtual event 

Prepared by: Becca Langstraat, Kate Biese, Krista Lachance, & Paul Nghiem 

Announcements 

1. The annual Merkel cell carcinoma Multi-Center Interest Group meeting is now being organized by the Merkel Cell Carcinoma Collaborative (MC3) Institute. As part of this transition, the MMIG listserv will be used to distribute the ‘MC3 Memos’ newsletter 2-4 times per year. If prefer to opt out of these communications, please contact [email protected]  
2. If you would like to view the meeting recording, please contact Kate directly ([email protected])
3. Please contact Paul Nghiem ([email protected]) or Kate Biese ([email protected]) if you would like to present at next year’s meeting or if you have any feedback to improve future meetings 

 

MMIG Meeting Agenda (times in EST)   

6:30-6:45pm	Welcome, Overview, and Intro to the Merkel Cell Collaborative (MC3) Institute	Paul Nghiem, MD/PhD (University of Washington)
6:45-7:00pm	Trial concept discussion: ctDNA as a Guide for Initiating Immune Therapy?	Tomoko Akaike, MD (University of Washington)
7:00-7:15pm	CD200 as a myeloid immune checkpoint in Merkel cell carcinoma	Yoshine (Jenny) Saito, BS (Dermatology Branch, NIAMS, NIH)
7:15-7:30pm	Outcomes after salvage for ICI-refractory MCC: What trials address this need?	Ariel Finberg, MD & Peter Ch’en, BS    (University of Washington)
7:30-7:35pm	BREAK
7:35-7:50pm	Single Fraction Radiation Therapy (SFRT) in MCC Updates	Emily Huynh, BS (Pacific Northwest University)
7:50-8:05pm	Developing Synergistic Drug Combinations for MCC	Khalid Garman, MD/PhD (Georgetown University)
8:05-8:20pm	Validating and Advancing MCC Prognostication: from Single-Institution Cohorts to Multi-Institution Data Integration	Aubriana McEvoy, MD (Washington University in St. Louis)
8:20-8:30pm	Closing remarks	Paul Nghiem, MD/PhD    (University of Washington)

 

Meeting notes: 

1. Trial Concept Discussion: ctDNA as a Guide for Initiating Immune Therapy? 

Tomoko Akaike, MD (University of Washington) 

• 40% recurrence rate – surveillance is important  

• ctDNA is an emerging blood test for surveillance 

• • MCC Tumor DNA is sequenced, and blood samples are analyzed to detect tumor DNA, providing a snapshot of MCC presence  

• Study on ctDNA utility in MCC: We evaluated ctDNA in 319 MCC patients, published in JCO 2024 (https://ascopubs.org/doi/abs/10.1200/JCO.23.02054). 

• • Compared to scans (gold standard) for detecting clinically evident MCC, ctDNA showed:  

• • • high sensitivity (94%-95%) and specificity (86%-90%) 

• • • Works for both VP and VN MCC 

• • ctDNA sensitivity for melanoma varies across stage 

• • • Stage III: ~35%, stage IV: 70-80% 

• Post-treatment implications of ctDNA results: 

• • Negative test: >97% chance of no recurrence within 90 days 

• • Positive test: 80% recur within 1 year,  

• • • 76% have ctDNA rise preceding clinical recurrence 

• Key Takeaways 

• • ctDNA detects recurrence earlier than imagaing, typically 

• • Broad adoption 

• • • Listed in NCCN guidelines for 2025 

• • • Reliable and accessible surveillance (blood draw possible at local clinic or even at home) 

• • • May reduce scan need for low-risk patients with negative ctDNA 

• • Current dilemma 

• • • If ctDNA positive but scans are negative: current standard practice is to “wait” for clinical/radiologic detection.  

• • • However, >80% will develop clinically evident disease by 1 year – very high risk if ctDNA pos 

• Fundamental question: Does early initiation of an immune checkpoint inhibitor (ICI) in ctDNA-positive pts, prior to clinically evident MCC, improve patient outcomes?  

• Relevant background: 

• • Current adjuvant trials: 

• • Higher risk patients offered ICI based on stage 

• • • STAMP: pembro for 1 year 

• • • ADAM: avelumab for 2 years 

• • Issues 

• • • Overtreatment: 30-70% would never have recurred without ICI 

• • • Early decision requirement, unable to enroll after eligibility period 

• Should ctDNA be used to identify higher-risk patients for more targeted ICI therapy? 

• • ctDNA allows de-escalation 

• • • most patients with moderate-risk disease will never become ctDNA positive and can be spared ICI toxicity/cost. 

• • • >80% with pos ctDNA develop clinical disease: 

• • • Far higher risk than even stage III MCC 

• • With ctDNA, patients can enroll at any time point they become positive 

• • • 60% of patients become ctDNA positive after 6 months of initial treatment 

• TRIAL: Should ctDNA positive patients get ICI? 

• • Eligible patients: locoregional (stage I-III) MCC patients, after initial curative treatment, no prior chemo/immunotherapy 

• • Subclinical MCC patients: 

• • • Positive ctDNA, Negative scans/physical exams 

• • • Randomize: observation vs. ICI (anti-PD(L)-1) 

• • • Both groups have ctDNA and scans every 3 mo 

• • • Major endpoints: recurrence-free survival, advanced disease-free recurrence, MCC-specific and overall survival, time to become ctDNA negative 

• • • Learn more on mc3institute.org if your institution may want to participate  

• Potential impact: Early initiation of ICI for subclinical MCC patients with positive ctDNA could: 

• • Shift current management and reduce exposure to potential toxicities and decrease the cost of therapies 

• • Increases quality of life and healthcare efficiency 

 

2. CD200 as a myeloid immune checkpoint in Merkel cell carcinoma 

Yoshine (Jenny) Saito, BS (Dermatology Branch, NIAMS, NIH) 

• MCC is highly immunogenic, ICIs are standard treatment for metastatic disease  

• • Only 40-60% respond to ICIs, new therapeutic approaches in need 

• CD200  

• • Expressed on many cell types 

• • • CD200R on monocytes, macrophages 

• • • CD200-CD200R interaction -> immunoregulatory signaling 

• • • Also expressed in many cancer cells  

• • Almost all MCC tumors express high levels of CD200 as well as immunosuppressive cell populations in the center and periphery of the tumor 

• • CD200 expressing MCC enhances M2 macrophage polarization and anti-inflammatory function 

• • • Direct cell-cell contact is required for M2 polarization 

• • • • Can be blocked by anti-CD200 antibody 

• • • CD200 is a cell surface ligand required for M2 polarization 

• • • Low CD200 is a biomarker for response to ICIs in MCC 

• • • • High CD200 had worse survival outcomes 

• CD200 is a promising myeloid immune synapse 

• Anti-CD200 agent could be used in combination with lymphoid immune blockade to further augment the management of MCC 

 

3. Outcomes after salvage for ICI-refractory MCC: what trials address this need? 

Ariel Finberg, MD & Peter Ch’en, BS (University of Washington) 

Salvage therapies for ICI-refractory MCC project in the Seattle cohort 

• Primary resistance: no response to first-line ICI  

• Acquired resistance: Initial positive response, followed by progression while on first-line ICI 

• • 44 primary resistance patients and 32 acquired resistance patients 

• Key takeaways 

• • Acquired resistance had better survival outcomes than primary resistance 

• Currently, there is not one salvage therapy approach that is better than the others à we need better treatments  

MCC Trials 

• Adjuvant Setting 

• • STAMP (adjuvant pembrolizumab) and ADAM (adjuvant avelumab) 

• • Both trials are closed to enrollment, data is being processed and coming out in the next year or so 

• PD-1 Refractory Setting 

• • TRICK-MCC (triple ICI: anti-LAG3, anti-TIM3 and anti-PD-1) 

• • • Closed to enrollment, data being processed 

• • MATRiX 

• • • Tuvusertib (ATR inhibitor with and without avelumab) 

• • IGNYTE 

• • • Injectable RP1 (modified herpes virus) with and without nivolumab 

• • Cullinan “CLN 617-001″ 

• • • Injectable IL2 +IL12 with or without pembrolizumab 

• ARTACUS 

• • Injectable RP1 (modified herpes virus) monotherapy for people with history of organ or hematopoietic transplant 

• Adjuvant Hypofractionated Radiation trial at MD Anderson Cancer Center (Texas) 

• • Less treatment visits, better quality of life, similar survival outcomes 

 

      4. Single Fraction Radiation Therapy (SFRT) in MCC Updates 

Emily Huynh, BS (Pacific Northwest University) 

• Conventional (greater than or equal to 50 Gy) postoperative RT (PORT): 

• • Decreases local recurrences by 3.7 fold  

• • Merkel cell carcinoma is very radiosensitive but 

• • • Conventional RT can cause significant side effects including delayed wound healing, lymphedema, etc.  

• • • Conventional RT is also inconvenient – 25 visits, distance to RT center 

• Currently 2 postoperative options 

• • Observation (increases risk) 

• • Conventional RT 

• 8Gy SFRT as a new postoperative option 

• Risk Factors for Recurrence including head/neck tumors, lymphovascular invasion, primary >1cm, immunosuppression, positive path margins 

• • 2 year local control rates 

• • • cPORT (4/156 recurred) 98% 

• • • SFRT (0/43 recurred) 100% 

• • • Observation (13/111 recurred) 91% 

• No significant difference between cPORT and SFRT 

• • SFRT is very well tolerated (82% of patients w/ 0 side effects) 

• • SFRT is better than observation which is what many sites offer 

• Benefits of SFRT – well tolerated and convenient 

• Limitations 

• • Not randomized 

• • Variable baseline risks 

• • Single-institution 

• Future direction: prospective validation across multiple institutions 

• • If your institution wants to participate, please learn more on mc3institute.org 

 

      5. Developing synergistic drug combinations for MCC 

Khalid Garman, MD, PhD 

• Immunotherapy is the first line treatment for metastatic MCC 

• • Durable responses achieved in less than 50% of patients 

• • Alternative treatments are needed 

• • Intersectional high-throughput screening methods 

• • • Pharmacological (small-molecule screening):  

• • • • single agent and combination screening 

• • • Functional genomics screening 

• • Identified 3 therapeutic targets for MCC 

• • • Aurora kinase B (VP-MCC > VN-MCC) 

• • • Histone deacetylases (VP-MCC) 

• • • Bcl-xL – part of the Bcl-2 family proteins (VP-MCC) 

• Bcl-xL is essential for VP-MCC viability 

• • Navitoclax inhibits Bcl-xL and is effective in VP-MCC both in vitro and in vivo 

• Challenges with Navitoclax 

• • Single dose causes a decrease in platelet number which can lead to 

• • • Thrombocytopenic purpura  

• • • Tumor hemorrhage in mice 

• To overcome this challenge: synergy matrix screen  

• • Lower Navitoclax, higher efficacy, and reduced risk of side effects 

• • Led to 8 target categories that synergized with Navitoclax including CDK inhibitors 

• • • Chose the CDK inhibitor Dinaciclib  

• • • Dinaciclib targets CDK 1/2/5/9 and was effective at decreasing VP and VN viability 

• Navitoclax and dinaciclib are synergistic in MCC which can enhance the potency of navitoclax without increased thrombocytopenia 

 

      6. Validating and Advancing MCC Prognostication: from Single-Institution Cohorts to Multi-Institution Data Integration 

Aubriana McEvoy, MD 

• Key tools for informing MCC patient prognosis 

• • AJCC 8th edition staging  

• • • Pathological vs. clinical stages 

• • • Overall survival from NCDB data  

• • Merkel cell polyomavirus (MCPyV) testing 

• • • AMERK serology, IHC, TMB from ctDNA 

• • • Virus positive pts have a better prognosis  

• • Circulating tumor DNA 

• • Recurrence risk calculator, Seattle based calculator 

• • • Age, sex, stage, site of primary, immunosuppression status 

• • • Improving the recurrence risk calculator 

• • • • External validation 

• • • • Calculator adjustments 

• • • • Possible future input variables for a recurrence risk calculator 2.0 

• • • • • Viral status at baseline 

• • • • Inform AJCC 9th edition staging 

• • • Why validate the MCC recurrence risk calculator? 

• • • • Demonstrates generalizability 

• • • • Can evaluate and improve model performance 

• • • • Builds trust in clinical implementation 

• • • Looking for multi-institution collaboration to validate and improve the recurrence risk calculator 

• Please contact Aubriana McEvoy at [email protected] if your institute is interested in participating   

 

—————————————————————————————————————————— 

Goals of the Merkel cell carcinoma Multi-center Interest Group (MMIG) – Promote communication and collaborative studies on MCC – Enhance access to patient data and specimens – Expand evidence-based care for MCC  

Homepage for MMIG is available at: https://merkelcell.org/about-us/mmig/ 

 

MMIG is funded in part by donations from Merkel cell carcinoma patients. Please note that in many cases, these summaries reflect unpublished data and are provided to help MMIG members manage their patients and give an overview of what is being done at different centers for care and research. 

 

In attendance at the 2025 MMIG Meeting (N=76 total attendees)  

Asterisk* = in-person attendee 

7 countries 

We apologize if we missed your name or affiliation 

 

Name	Institution
Afanasiev, Olga	Sutter Health, San Francisco, US
*Akaike, Tomoko	University of Washington School of Medicine, Seattle, US
Andrew, Tom	Newcastle University, Newcastle upon Tyne, England
Ashby, Sherry	Patient
Becker, Jürgen	University Medicine Essen and German Cancer Consortium, Essen, Germany
Bencomo, Tomas	University of Washington School of Medicine, Seattle, US
Berlinsky, Leslie	Patient/community
*Bichakjian, Chris	University of Michigan Medical School, Ann Arbor, US
Bhakuni, Rashmi	University of Washington School of Medicine, Seattle, US
Biese, Kate	University of Washington School of Medicine, Seattle, US
Bouché, Nicole	WSU Elson S. Floyd College of Medicine, Spokane, US
Brownell, Isaac	National Institutes of Health, Bethesda, US
*Camargo, Anthony	University of Massachusetts Medical School, Worcester, US
Chandrasekhar, Smitha	University of Washington School of Medicine, Seattle, US
*Ch’en, Peter	University of Washington School of Medicine, Seattle, US
Chi, Junlong	Feinberg School of Medicine at Northwestern University, Chicago, US
Church, Candice	University of Washington School of Medicine, Seattle, US
Coxon, Amy	National Institutes of Health, Bethesda, US
Dudzisz-Sledz, Monika	Maria Sklodowska-Curie National Research Institute of Oncology, Warsaw, Poland
*Finberg, Ariel	University of Washington School of Medicine, Seattle, US
Gao, Ling	University of California Irvine School of Medicine, Irvine, US
Garman, Khalid	National Institutes of Health, Bethesda, US
Hallaert, Patrick	National Institutes of Health, Bethesda, US
Hancock, Elaine	Patient/community
Hansen, Tucker	Washington University in St. Louis, St. Louis, US
*Harms, Kelly	University of Michigan Medical School, Ann Arbor, US
Hippe, Dan	Fred Hutchinson Cancer Center, Seattle, US
Hicks, Debra	Patient/community
Hsu, Charles	University of Arizona College of Medicine, Tucson, US
*Huynh, Emily	Pacific Northwest University-Health Sciences, Yakima, US
Igras, Leon	EH&S Consultant, Scottsdale, US
Jones, Brenda	Patient/community
*Kattapuram, Nathan	Georgetown University, Washington D.C., US
Kelley, Sue	Patient/community
Khaddour, Karam	Dana-Farber Cancer Institute, Boston, US
Koh, Young Wha	Ajou University, Suweon, Korea
Kulikauskas, Rima	University of Washington School of Medicine, Seattle, US
Lachance, Krista	University of Washington School of Medicine, Seattle, US
Landers, Stewart	Patient/community
Little, Alicia	Yale School of Medicine, New Haven, US
Lombard, Lawrence	Patient/community
Marković, Jasminka	Patient/community
*McClure, Erin	Oregon Health Sciences University, Portland, US
*McEvoy, Aubri	Washington University in St. Louis, St. Louis, US
Mehmi, Inderjit	The Angeles Clinic, Los Angeles, US
Meltzer, Jasmine	National Institutes of Health, Bethesda, US
Miller, David	Massachusetts General Hospital, Boston, US
Minutilli, Ettore	Catholic University of the Sacred Heart, Milan, Italy
Miao, Lingling	National Institutes of Health, Bethesda, US
Morris, Valerie	EMD Serono
Mowery, Yvonne	University of Pittsburgh Medical Center, Pittsburgh, US
Moynihan, Devin	University of Washington School of Medicine, Seattle, US
*Murchison, Kyle	Brigham and Women’s Hospital, Boston, US
*Nghiem, Paul	University of Washington School of Medicine, Seattle, US
Ouellette, Scotia	University of Washington School of Medicine, Seattle, US
Park, Soo	University of California San Diego Health, San Diego, US
Rodriguez, Haroldo	University of Washington School of Medicine, Seattle, US
*Saito, Jenny	National Institutes of Health, Bethesda, US
Schweitzer, Lynn	Patient/community
Scott, Michael	Pacific Northwest University-Health Sciences, Yakima, US
Shalhout, Sophia	Massachusetts General Hospital, Boston, US
*Silk, Ann	Dana-Farber Cancer Institute, Boston, US
Shover, Jennifer	Patient/community
Sober, Arthur	Massachusetts General Hospital, Boston, US
Szumera, Anna	Maria Sklodowska-Curie National Research Institute of Oncology, Warsaw, Poland
*Tarabadkar, Erica	Olansky Dermatology & Aesthetics, Atlanta, US
Thakuria, Manisha	Brigham and Women’s Hospital, Boston, US
Topalian, Suzanne	Johns Hopkins School of Medicine, Baltimore, US
Tsai, Ken	Moffitt Cancer Center, Tampa, US
Turaka, Aruna	Penn State Cancer Institute, Hershey, US
Webster, Louise	Patient/community
Wilk, Victoria	University of Washington School of Medicine, Seattle, US
Xu, Wen	Princess Alexandra Hospital, Brisbane, Australia
Yu, Siegrid	University of California San Francisco, San Francisco, US
Yousefiasl, Maya	Fred Hutchinson Cancer Center, Seattle, US
*Zaba, Lisa	Stanford Medical Center, Palo Alto, US