Summary of The 17th Annual MMIG Meeting

Below is a summary of the 17th Annual MMIG Meeting. Notably, there were 87 total attendees with 17 in person and 70 virtual, and there was a total of 10 countries represented.

Summary of 17^th Annual MMIG Meeting

(Merkel cell carcinoma Multi-Center Interest Group)

Friday, March 17th, 2023

New Orleans, LA & Virtual event

Prepared by:

Rian Alam, Kate Biese, Krista Lachance, Ankita Menon, & Paul Nghiem

Announcements

1. If you would like to view the meeting recording, please contact Kate directly ([email protected])
2. 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 CDT)

5:00-5:10pm	Welcome & Overview of Meeting	Paul Nghiem, MD/PhD (University of Washington)
5:10-5:25pm	Margin Status and the Role of Adjuvant Radiation in MCC: The Australian Experience	David Kok, MBBS/MEd (Peter MacCallum Cancer Centre)
5:25-5:40pm	Virus Positive MCC in Skin of Color and Impact on Disease Outcomes	Mackenzie Martin, BA (Brownell Lab, NIH/NIAMS)
5:40-5:55pm	Clinical Trial Updates for MCC	Erin McClure, BS & Neha Singh, BS (University of Washington)
5:55-6:00pm	BREAK
6:00-6:15pm	An Emerging Radiotherapy Option for MCC Patients: 8 Gray Single Fraction	Emily Huynh, BS (University of Washington)
6:15-6:30pm	Baseline MCC Imaging with Ultrasound and PET/CT: A Comparison	Lisanne Zijlker, PhD candidate (Melanoma Institute Australia)
6:30-6:45pm	Utility of Circulating Tumor DNA to Monitor Treatment Response and Recurrence	Lisa Zaba, MD/PhD (Stanford University) & Tomoko Aikaike, MD (University of Washington)
6:45-6:55pm	SATB2, CKAE1/AE3, and Synaptophysin as a Sensitive Immunohistochemical Panel for the Detection of Lymph Node Metastases of MCC – A Multicenter Study	Anna Szumera-Ciećkiewicz, MD/PhD (Maria Sklodowska-Curie National Research Institute of Oncology) & Piotr Donizy, MD/PhD (Wroclaw Medical University)*
6:55-7:00pm	Closing remarks	Paul Nghiem, MD/PhD (University of Washington)

 

Meeting notes:

 

1. Margin Status and the Role of Adjuvant Radiation in MCC: The Australian Experience

David Kok, MBBS/MEd (Peter MacCallum Cancer Centre (PMCC))

 

• Highest world MCC occurrence rate is in Victoria Australia, 2.5 / 100,000 persons (Garbutcheon-Singh 2019)
• Australian treatment heavily utilizes radiotherapy- protocol has been adjuvant RT regardless of margin status
• Retrospective audit of 533 PMCC patients 1980 – 2019
  • Includes: pts with dx of MCC, received treatment at PMCC, minimum follow up time of 12 mo, staged via 8^th edition staging system
• Patient age, immunosuppression status, and nodal status were statistically significant for disease free survival. Gender, tumor size, and margins did not have statistical significance
• Largest single institution MCC cohort study published to date
  • Conclusions: If radiation is given, no difference in outcomes between patients with positive and negative surgical margins even when accounting for immunosuppression and other risk factors
  • It is unclear if there is a benefit to pursuing 1-2cm margins in absence of difference of patient outcomes

2. Virus Positive MCC in Skin of Color and Impact on Disease Outcomes

Mackenzie Martin, BA (Brownell Lab, NIH/NIAMS)

 

• MCC primarily occurs in White patients
• Hispanic patients have improved Disease Specific Survival (DSS) compared to White patients while Black and Asian American and Pacific Islander (AAPI) patients have no difference compared to White patients
• UV driven MCC (Virus negative, VN) has worse DSS than non-UV dependent MCC (Virus positive, VP) (Harms et al. 2021)
• Black and Hispanic patients are less likely to have MCC of the head and neck
• Meta analysis shows that relative to VN-MCC, VP-MCC is more likely to occur on UV protected sites
• VN-MCC incidence positively correlates with environmental UV exposure while VP-MCC incidence does not (global regression)
• VP-MCC more common in Black and Hispanic patients
• Conclusions: Black and Hispanic patients -> VP-MCC -> better DSS -> masks racial and ethnic disparities

 

3. Clinical Trial Updates for MCC

Erin McClure, BS & Neha Singh, BS (University of Washington)

Summarized in tabular form:

Trial type:	Name of trial:	Details:	NCT:
Adjuvant   *must have NED at start of study	ADAM*	IMTX (avelumab) or placebo 2 years. Nearing complete enrollment, ~88/100 patients.	NCT03271372
	STAMP*	Stage 1-3 at dx. IMTX (Keytruda) or observation. 1 year. Completed enrollment of 280/280 patients.	NCT03712605
	ADMECO	2:1 Nivo vs observation Stage ¾. observation. Nivo group had 44% reduction in recurrences, p-value is not significant at p=0.109.	NCT02196961
	Vaccine Trial	First ever human MCC vaccine trial, focused on assessing safety of vaccine. Designed to boost anti-Merkel cell polyomavirus immunity. Assess T cell and B cell response to determine next steps.	NCT05422781
Anti-PD-(L)1 Refractory	Checkmate	Intratumoral TLR-9 agonist with an anti-PD1 agent (cemiplimab)	NCT04916002
	ATTAC	Patients are pretreated with IFN-y to improve MHC class I upregulation Treatment: IFN-y + genetically modified T-cells to target MCPyV +/- avelumab (if immunotherapy previously well tolerated)	NCT03747484
	Kartos	Inhibits MDM2 which prevents degradation of p53	NCT03787602
Anti-PD-(L)1 Refractory trials coming soon	MATRiX	ATR inhibitor +/- avelumab
	TRICk MCC	Triple checkpoint blockade: anti-TIM3 + anti-LAG3 + anti-PD1 agent

 

4. An Emerging Radiotherapy Option for MCC Patients: 8 Gray Single Fraction

Emily Huynh, BS (University of Washington)

 

• Single fraction radiation therapy (SFRT) = 8 Gy in one fraction. Can be used as post-operative radiation therapy (PORT)
• Pros and cons of conventional radiation (50 Gy or more)
  • Pros: Conventional PORT improves disease-free survival
  • Cons: significant side effects, inconvenience (~25 or more trips to RT center)
• Who should get PORT?
  • Need depends on baseline risk factors (even one of six risk factors may justify): Lymphovascular invasion, immunosuppression, primary >2 cm, head/neck primary, + path margins, + nodes
• Low to medium risk factors can get SFRT PORT – efficacy analyzed in this retrospective study
  • Stage I-II pts who got 8 Gy SFRT to primary site following Wide Local Excision/Mohs/biopsy
  • Conclusions: Observed a 96% in-field control rate (much higher than the expected 70% given the risk profile of the cohort) (Takagishi et al. 2016)
  • Patients also reported few side effects (SFRT –> minimal toxicity)

5. Baseline MCC Imaging with Ultrasound and PET/CT: A Comparison

Lisanne Zijlker, PhD candidate (Melanoma Institute Australia)

 

• Merkel patients frequently have metastases at diagnosis (nodal 15-32%, distant 7-8%) (Harms et al. 2016, Uitentuis et al. 2019), important to do adequate staging at diagnosis before resection or sentinel lymph node biopsy (SLNB)
  • Pre-operative upstaging can adjust treatment (Lymph node dissection vs SLNB)
• Retrospective study to analyze diagnostic value of ultrasound (US) vs PET/CT at baseline for pts w localized MCC & nodal metastases
  • 104 Stage I/II and Stage III pts who underwent US or PET/CT at Netherlands Cancer Insititute 2015-2021
    • Performed within 90 days after dx
  • US had sensitivity of 40%, specificity of 100%, 31% false negative
    • US after PET/CT identified 46% false negative and 25% lymph node metastases
  • Results indicate that PET/CT has highest rate of upstaging (26%) (Zijlker et al. 2022)
    • US has 19% rate of upstaging
      • Benefit is low cost and no radiation risk
    • High false positive rates for both (23% PET/CT, 16% US)
    • Stage I/II frequently upstaged to Stage III by both US (19%) and PET/CT (26%)
    • PET/CT prior to US+FNAC enhances US sensitivity
      • Shows FDG-avid lymph node
    • Conclusions: PET/CT is the most sensitive imaging modality, upstaging 26% of pts
      • SLNB remains most reliable method of staging for nodal mets

6. Utility of Circulating Tumor DNA to Monitor Treatment Response and Recurrence

Lisa Zaba, MD/PhD (Stanford University) & Tomoko Akaike, MD (University of Washington)

 

• ctDNA test: Sequence tumor DNA and blood DNA (control) and design custom PCR tests
• ctDNA has been established in other cancers such as colon, breast, lung, etc. (Coombes et al. 2019, Peter et al. 2005, Reinert et al. 2019, Abbosh et al. 2017)
• Study incorporated 319 pts from 6 sites (167 in discovery cohort, 152 in validation cohort)
  • Sensitivity: 94-95% of patients w/ MCC did have positive ctDNA draw at diagnosis
  • Specificity: 86-90%, meaning 10-14% pts did have a positive ctDNA without clinically evident disease
  • “False positives” likely due to ctDNA detecting sub-clinical disease
  • 5-20 fold risk of developing recurrence if ctDNA positive
  • Median lead time to detect + ctDNA test on imaging, etc., = 55 days
  • Negative predictive value of ~97% 90 days out
• Conclusions: ctDNA status is strongly predictive of disease status and RFS
  • SLNB still needed to stage node-negative patients
  • Can we use this for adjuvant treatment? Highly predictive of recurrence

 

7. SATB2, CKAE1/AE3, and Synaptophysin as a Sensitive Immunohistochemical Panel for the Detection of Lymph Node Metastases of MCC – A Multicenter Study

Anna Szumera-Ciećkiewicz, MD/PhD (Maria Sklodowska-Curie National Research Institute of Oncology) & Piotr Donizy, MD/PhD (Wroclaw Medical University)*

 

• Background: Micrometastatic MCC cells are very difficult to identify in lymphoid cells
  • Immunostains can increase sensitivity of IDing lymph node mets, but there is no protocol
• Study aimed to examine effectiveness of wide-spectrum panel of IHC (CKAE1/AE3, CK20, chromogranin A, synaptophysin, NF, INSM1, SATB2, MCPyV) to detect single-cell metastatic MCC using 56 MCC pts w/ regional lymph node mets
  • Select most appropriate antibodies for histopathological evaluation of lymph nodes in MCC
• Results showed that CKAE1/AE3, SATB2, and synaptophysin were characterized with the highest cumulative percentage of positive reaction. There were no entirely negative cases for these 3 markers
• SATB2 has highest sensitivity in detecting metastatic MCC cells
  • 89% of all metastatic nodes were characterized by moderate – strong SATB2 expression
• CKAE1/AE3 had comparable sensitivity, but has the disadvantage that nodal dendritic cells can be focally positive with weak to moderate intensity
• Synaptophysin was third most sensitive at 78%, CK20 had lowest sensitivity at 59%
• Conclusion: Propose using CKAE1/AE3, SATB2, and synaptophysin in routine MCC SLNB/LND

*Complete list of co-authors

Anna Szumera-Cieckiewicz, Daniela Massi, Angelo Cassisa, Mateusz Krzyzinski, Monika Dudzisz-Sledz, Przemyslaw Biecek, Piotr Rutkowski, Andrzej Marszalek, Mai P. Hoang, Piotr Donizy

 

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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 2023 MMIG Meeting (N=87 total attendees)

Asterisk* = in-person attendee

We apologize if we missed your name or affiliation

 

Alexander, Nora	Washington University in St. Louis, St. Louis, US
*Andrews, Courtney	Meharry Medical College, Nashville, US
*Andrews, Philip	Chattanooga Skin and Cancer, Chattanooga, US
Asioli, Sofia	University of Bologna, Bologna, Italy
*Baltazar, David	HonorHealth
Bhakuni, Rashmi	University of Washington, Seattle, US
Bierma, Marika	CalmWave
Biese, Kate	University of Washington, Seattle, US
Blom, Astrid	Ambroise Pare Hospital, Boulogne, France
Bollin, Kathryn	Scripps MD Anderson, San Diego, US
Brownell, Isaac	National Institutes of Health, Bethesda, US
Caneborg, Alex	University of Melbourne, Melbourne, Australia
*Chan, Tiffanie	Kartos Therapeutics
Christie, David	GenesisCare, Melbourne, Australia
Daniels, Gregory	University of California San Diego, San Diego, US
DeCaprio, James	Dana-Farber Cancer Institute, Boston, US
*Donizy, Piotr	Wroclaw Medical University, Poland
Dudzisz Sledz, Monika	Maria Sklodowska-Curie National Research Institute of Oncology, Warsaw, Poland
Finberg, Ariel	Virginia Mason, Seattle, US
Fu, Teresa	Palo Alto Medical Foundation, Palo Alto, US
Gao, Ling	Long Beach VA / University of California, Irvine, US
Garman, Khalid	National Institutes of Health, Bethesda, US
Gaughan, Liz	University of Virginia, Charlottesville, US
Goff, Peter	University of Washington, Seattle, US
Hanson, Sarah	Pfizer
Harikrishnan, Nikhil	University of Washington, Seattle, US
Hill, Natasha	National Institutes of Health, Bethesda, US
Hippe, Dan	Fred Hutchinson Cancer Center, Seattle, US
Hong, Angela	Melanoma Institute Australia, Wollstonecraft, Australia
Hsu, Charles	University of Arizona Cancer Center, Tucson, US
Huynh, Emily	University of Washington, Seattle, US
Jarvis, Jordan	National Institutes of Health, Bethesda, US
*Kasprzak, Julia	Medical College of Wisconsin, Milwaukee, US
*Kim, Emily	Dana-Farber Cancer Institute, Boston, US
Kok, David	Peter MacCallum Cancer Centre, Melbourne, Australia
Lachance, Krista	University of Washington, Seattle, US
Liao, Yi-Hua	National Taiwan University Hospital, Taipei, Taiwan
Lin, Rongxiang	University of Washington, Seattle, US
Lipson, Evan	Johns Hopkins University, Baltimore, US
Lobo, Matheus	A C Camargo Cancer Center, Sao Paulo, Brazil
Lombard, Lawrence	Patient
Ma, Vincent	University of Wisconsin, Madison, US
*Martin, Mackenzie	National Institutes of Health, Bethesda, US
*McClure, Erin	University of Washington, Seattle, US
Mehmi, Inder	The Angeles Clinic and Research Institute, Los Angeles, US
Miao, Lingling	National Institutes of Health, Bethesda, US
Miller, David	Massachusetts General Hospital, Boston, US
Minutilli, Ettore	Catholic University of the Sacred Heart, Milan, Italy
Morris, Valerie	EMD Serono
Nagase, Kotaro	Saga-Ken Medical Center Koseikan, Saga, Japan
Nakamura, Motoki	Nagoya City University, Nagoya, Japan
Nallagangula, Aparna	Banner – University Medical Center Tucson, Tuscon, US
*Nghiem, Paul	University of Washington, Seattle, US
Olino, Kelly	Yale University, New Haven, US
*Paoli, John	University of Gothenburg, Gothenburg, Sweden
*Park, Song	University of Washington, Seattle, US
Park, Soo	University of California, San Diego, US
Pincus, Jonathan	Patient
Rabinowits, Guilherme	Miami Cancer Center, Miami, US
Rady, Peter	McGovern Medical School, Houston, US
Reddy, Sunil	Stanford Medical Center, Palo Alto, US
Reed, Danielle	NIAMS
Rodriguez, Haroldo	University of Washington, Seattle, US
Rodriguez, Juan	EMD Serono
Russell, Mark	University of Virginia, Charlottesville, US
Rutkowski, Piotr	Maria Sklodowska-Curie National Research Institute of Oncology, Warsaw, Poland
Saiag, Philippe	Ambroise Pare Hospital, Boulogne, France
Shalhout, Sophia	Massachusetts General Hospital, Boston, US
Silk, Ann	Dana-Farber Cancer Institute, Boston, US
*Singh, Neha	University of Washington, Seattle, US
Soapes, Page	Bristol-Myers Squibb
Sober, Arthur	Massachusetts General Hospital, Boston, US
Sondak, Vernon	Moffitt Cancer Center, Tampa, US
Stirewalt, Robin	Patient
*Szumera-Ciećkiewicz, Anna	Maria Skłodowska-Curie Institute of Oncology, Warsaw, Poland
Thakuria, Manisha	Brigham and Women’s Hospital, Boston, US
Tothill, Richard	University of Melbourne, Australia
Turaka, Aruna	Nazareth Hospital, Philadelphia, US
Villabona, Lisa	Karolinska University Hospital, Stockholm, Sweden
Wang, Richard	UT Southwestern, Dallas, US
Wittal, Richard	University of New South Wales, Sydney, Australia
*Wong, Michael	MD Anderson Cancer Center, Houston, US
Wratten, Chris	Calvary Mater Newcastle, Waratah, Australia
Yu, Siegrid	University of California, San Francisco, US
*Zaba, Lisa	Stanford Medical Center, Palo Alto, US
*Zeithouni, Nathalie	Phoenix, AZ
Zijlker, Lisanne	Netherlands Cancer Institute, Amsterdam, Netherlands