Summary of The 16th Annual MMIG Meeting
April 12, 2022
American Academy of Dermatology Annual Meeting
Boston, MA
Prepared by: Marika Bierma, Alex Fu, Nikhil Harikrishnan, Ally Remington, Krista Lachance, and Paul Nghiem
Agenda
1. Utility of a circulating tumor DNA test for detecting clinically evident and occult Merkel cell carcinoma
Lisa Zaba, MD, PhD (Stanford University)
2. Indolent MCC: Immune and Tumor Balance
Aubriana McEvoy, MD (Washington University)
3. A practical approach to interpreting MCPyV oncoprotein titers in MCC
Lindsay Gunnell, MD (University of Washington)
4. Real world assessment of ipi-nivo in anti-PD-(L)1 refractory Merkel cell carcinoma
Sophia Shalhout, PhD (Mass General Hospital)
5. Health disparities in Merkel cell carcinoma: an examination of racial disparities
Mackenzie Martin, BA (Brownell Lab, NIAMS, NIH)
6. Improvement of the histopathological detection of Merkel cell carcinoma lymph node metastases- preliminary results of a multicentric cohort study
Anna Szumera-Ciećkiewicz, MD, PhD (Maria Sklodowska-Curie National Research Institute of Oncology) & Piotr Donizy, MD, PhD (Wroclaw Medical University)
Meeting minutes
1. Utility of a circulating tumor DNA test for detecting clinically evident and occult Merkel cell carcinoma
Lisa Zaba, MD, PhD (Stanford University)
• Surveillance is key when approaching Merkel cell carcinoma due to its rapid growth rate and relatively high recurrence rate (40%).
• Currently, there is no clinically available blood test that provides recurrence monitoring data for all patients regardless of Merkel polyomavirus (MCPyV) serologic status.
o AMERK serology (which detects MCPyV oncoprotein antibodies) is limited since only ~50% of MCC patients produce these antibodies at the time of disease.
• ctDNA tracking can be useful for MCC patients regardless of MCPyV status and provides real time indication of disease (half-life: <2 hours)
o Found a positive correlation between tumor size and level of ctDNA (n=24), regardless of MCPyV status.
• Among University of Washington and Stanford patients, interim analysis suggests that ctDNA can be an accurate predictor of developing MCC with a specificity of 91% (n=120). Specifically, if a patient has a negative ctDNA test, we can be fairly confident that it will remain negative 60-90 days later.
• Working on multicenter prospective study, combining data from ~180 MCC patients with 400 longitudinal time points.
2. Indolent MCC: Immune and Tumor Balance
Aubriana McEvoy, MD (Washington University)
• Retrospectively identified 13 patients with advanced MCC, no systemic therapy, and lengthy overall survival (>5 years since MCC diagnosis) from the UW MCC database.
• In patients with significant comorbidities and/or desire to avoid systemic therapy, MCC may be relatively well-controlled with surgery and/or radiation alone.
o Hypothesis: in these indolent MCC cases, the immune system is in balance with the disease.
• Single fraction radiation therapy can be effective in indolent MCC patients, with minimal side effects, by possibly stimulating the immune system.
• Merkel cell polyomavirus oncoprotein antibody (AMERK) test is a sensitive marker of MCC disease burden in virus-positive patients.
• Further studies will be helpful to identify what characteristics predict an indolent course of disease without systemic therapy.
3. A practical approach to interpreting MCPyV oncoprotein titers in MCC
Lindsay Gunnell, MD (University of Washington)
• The AMERK serology test (which detects oncoprotein antibodies) can be a sensitive, safe, and convenient way to monitor patients in the long-term. It can sometimes precede detection of recurrence via imaging by 12-15 months.
• Seattle MCC patient cohort data suggest that ~70% of patients with rising titers develop clinically evident disease (~30% recurred within 90 days, ~30% recurred greater than 90 days – 1 year, 10% recurred greater than 1 year).
• After the first year, falling antibody titers have high negative predictive value in confirming no active disease. In these cases, scans can be safely stopped, but interval antibody testing should be continued.
• Discontinuation of antibody testing should be individualized.
o If antibody testing remains undetectable (<74) for 4-5 years post-diagnosis, testing can likely be safely discontinued.
4. Real world assessment of ipi-nivo in anti-PD-(L)1 refractory Merkel cell carcinoma
Sophia Shalhout, PhD (Mass General Hospital)
• In a retrospective study of 13 patients who received second or third line ipi-nivo after progressing on first-line immune checkpoint blockade (anti-PD-(L)-1), 77% patients had progressive disease and 23% of patients had stable disease. There were no complete or partial responses to second or third line ipi-nivo.
• These data demonstrate that Ipi-nivo often has disappointing efficacy for anti-PD-(L)-1 refractory MCC.
• New strategies for second-line treatment of MCC are needed, and referral to innovative clinical trials should be a priority for these refractory MCC patients.
5. Health disparities in Merkel cell carcinoma: an examination of racial disparities
Mackenzie Martin, BA (Brownell Lab, NIAMS, NIH)
• As the proportion of minority MCC patients is increasing, it is important to consider racial disparities in the treatment of these patients.
• Hispanic MCC patients appear to have increased disease-specific survival rates compared to White MCC patients, which is a novel observation. This may be due to the Hispanic Health Paradox hypothesis, but further research on this topic is needed and this finding may be due to the limitations of the SEER cancer registry.
• Prominent MCC-specific socioeconomic determinants of health include wait times and delayed treatment of MCC in minority populations, and hospital characteristics (high volume vs. low volume facilities).
• Improving the capture of race in data registries and increasing the representation of minority populations in clinical trials are critical to addressing and eliminating racial disparities in MCC.
6. Improvement of the histopathological detection of Merkel cell carcinoma lymph node metastases- preliminary results of a multicentric cohort study
Anna Szumera-Ciećkiewicz, MD, PhD (Maria Sklodowska-Curie National Research Institute of Oncology) & Piotr Donizy, MD, PhD (Wroclaw Medical University)
• Preliminary results based on 28 MCC metastatic lymph node samples (final database consists of 136 lymph node samples from 77 MCC patients); researchers created tumor microarrays to determine the efficacy of different histopathological stains in detecting MCC in the lymph nodes.
• A combination of IHC markers is recommended for MCC lymph node histopathologic examination.
• SATB2, synaptophysin, and INSM1 are the top three markers with the highest cumulative percentage of positive reaction while SATB2, panCK, and chromogranin are markers with the highest 100% positivity.
• Preliminary results indicate the important role of SATB2 in detecting MCC nodal metastases as it has the highest sensitivity in detecting MCC metastatic cells, even in CK20-negative cases.
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.