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

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.

Figure 1.. Outcomes stratified by baseline AMERK level.

(A) Event-free survival for patients with positive baseline AMERK level compared to patients with negative baseline AMERK level. (B) Cumulative incidence of Merkel cell carcinoma-associated recurrence for patients with positive baseline AMERK level compared to patients with negative baseline AMERK level with non-Merkel cell carcinoma-related death as competing risk.

Figure 1.. Outcomes stratified by baseline AMERK level.

(A) Event-free survival for patients with positive baseline AMERK level compared to patients with negative baseline AMERK level. (B) Cumulative incidence of Merkel cell carcinoma-associated recurrence for patients with positive baseline AMERK level compared to patients with negative baseline AMERK level with non-Merkel cell carcinoma-related death as competing risk.

Figure 2.. Changes in AMERK level after radiotherapy

(A) AMERK values (log transformed) over time by MCC-related relapse event (n=48). (B) Swimmer plot showing time to RFS event or last MCC assessment with symbols depicting time of maximum % decrease in AMERK value from baseline (n=48). Closed circles: indicates time at nadir (lowest value) among patients that had persistent positive AMERK or had less than 50% decrease. Close triangles: indicates time at which AMERK became undetectable or decreased by at least 50%.

Figure 2.. Changes in AMERK level after radiotherapy

(A) AMERK values (log transformed) over time by MCC-related relapse event (n=48). (B) Swimmer plot showing time to RFS event or last MCC assessment with symbols depicting time of maximum % decrease in AMERK value from baseline (n=48). Closed circles: indicates time at nadir (lowest value) among patients that had persistent positive AMERK or had less than 50% decrease. Close triangles: indicates time at which AMERK became undetectable or decreased by at least 50%.

Figure 3.. Outcomes stratified by changes in AMERK level from baseline at 6 months after radiation.

(A) Event-free survival for patients with positive baseline AMERK level and achieved either borderline AMERK level or ≥50% decrease in AMERK level at 6 months after radiation compared to patients with AMERK levels >150 and <50% decrease. (B) Cumulative incidence of Merkel cell carcinoma-associated recurrence for patients with positive baseline AMERK level and achieved either borderline AMERK level or ≥50% decrease in AMERK level at 6 months after radiation compared to patients with AMERK levels >150 and <50% decrease with non-Merkel cell carcinoma-related death as competing risk.

Figure 3.. Outcomes stratified by changes in AMERK level from baseline at 6 months after radiation.

(A) Event-free survival for patients with positive baseline AMERK level and achieved either borderline AMERK level or ≥50% decrease in AMERK level at 6 months after radiation compared to patients with AMERK levels >150 and <50% decrease. (B) Cumulative incidence of Merkel cell carcinoma-associated recurrence for patients with positive baseline AMERK level and achieved either borderline AMERK level or ≥50% decrease in AMERK level at 6 months after radiation compared to patients with AMERK levels >150 and <50% decrease with non-Merkel cell carcinoma-related death as competing risk.