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. 2024 Dec 15;130(24):4267-4275.
doi: 10.1002/cncr.35507. Epub 2024 Aug 5.

Changes in Merkel cell oncoprotein antibodies after radiation therapy in curatively treated Merkel cell carcinoma and association with recurrence

Kevin X Liu  1 , Kee-Young Shin  2 , Manisha Thakuria  3   4 , Jonathan D Schoenfeld  1   3 , Roy B Tishler  1   3 , Ann W Silk  3   5 , Charles H Yoon  3   6 , Elliott Fite  1 , Danielle N Margalit  1   3
Affiliations

Changes in Merkel cell oncoprotein antibodies after radiation therapy in curatively treated Merkel cell carcinoma and association with recurrence

Kevin X Liu et al. Cancer. .

Abstract

Background: Serum antibodies to the Merkel oncoprotein (AMERK) are detectable in approximately 50% of patients with Merkel cell carcinoma (MCC) and can be used to monitor for recurrence. The objective of this study was to characterize AMERK levels in patients receiving curative-intent radiation therapy (RT) for MCC and identify associations between AMERK and recurrence.

Methods: This was a retrospective study of patients with MCC who had baseline AMERK measurements before they received curative-intent RT from 2010 to 2020. Event-free survival (EFS) was calculated using the Kaplan-Meier method and Cox regression. The cumulative incidence of MCC-related recurrence (CIMR) was analyzed with death as a competing risk and the Gray test.

Results: The authors identified 88 patients who had baseline AMERK measurements, including 52 (59%) with detectable levels. AMERK positivity was associated with younger median age (67.8 vs. 72.0 years; p = .02) and tumor site (p = 0.02), with lower rates for those who had disease in the head/neck region (17.3% vs. 44.4%). EFS (71.3% vs. 60.4%; p = .30) and CIMR (24.4% vs. 39.6%; p = .23) were more favorable in AMERK-positive patients. Two patients had recurrences in the RT field, and both were AMERK-negative at baseline. The median time to AMERK nadir after RT was 11.2 months; and, in a 6-month post-RT landmark analysis, the proportion of patients who were AMERK-positive who became negative or who had levels that decreased by ≥50% were not associated with EFS (87.1% vs. 85.0%; p = .90) or CIMR (12.9% vs. 15.0%; p = .62).

Conclusions: Positive AMERK baseline levels were correlated with younger age at MCC diagnosis and nonhead and neck tumor location, possibly related to the distribution of viral etiology. A specific post-RT AMERK decline correlating with EFS could not be identified.

Keywords: Merkel cell carcinoma (MCC); Merkel cell oncoprotein antibodies (AMERK); antibody; radiation therapy; recurrence.

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Conflict of interest statement

Conflicts of Interest: JDS reports research support paid to the institution: Merck, BMS, Regeneron, Debiopharm, EMD Serono. Consulting / Scientific Advisory Board / Travel fees: Castle Biosciences, Genentech, Immunitas, Debiopharm, BMS, Nanobiotix, Tilos, AstraZeneca, LEK, Catenion, ACI Clinical, Astellas, Stimit, EMD Serono. Expert witness fees. Stock options: Immunitas. Equity: Doximity. AWS reports research support paid to the institution from Replimune, Morphogenesis, Regeneron, and Merck, advisory board fees from Natera, Merck and Regeneron, and royalties from UpToDate, Inc. MT reports advisory board fees from Incyte.

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