Complete Response of Merkel Cell Carcinoma to Immunotherapy and Single-Fraction Radiotherapy Following Severe COVID-19 Infection: A Case Report and Review of Immune Mechanism
Restricted accessResearch articleFirst published online 2026
Complete Response of Merkel Cell Carcinoma to Immunotherapy and Single-Fraction Radiotherapy Following Severe COVID-19 Infection: A Case Report and Review of Immune Mechanism
Merkel cell carcinoma (MCC) is a rare, aggressive neuroendocrine form of skin cancer. This case report describes a 70-year-old Hispanic male with stage IIA MCC of the upper back which rapidly progressed during hospitalization for severe COVID-19 infection requiring ventilatory support. After resolution of his severe acute illness, he received one dose of anti-PD-1 therapy and single-fraction radiotherapy to his primary lesion for local control. His tumor then underwent a rapid regression and he completed 17 cycles of immunotherapy with a complete clinical and radiologic response sustained more than 4 years. This case illustrates a possible synergistic effect of radiation therapy and immune checkpoint inhibition after rebounding immune-system hyperactivation from infection with COVID-19.
NghiemPTBhatiaSLipsonEJ, et al.PD-1 blockade with pembrolizumab in advanced merkel-cell carcinoma. N Engl J Med. 2016;374(26):2542-2552. doi:10.1056/NEJMoa1603702.
5.
TopalianSLBhatiaSAminA, et al.Neoadjuvant nivolumab for patients with resectable merkel cell carcinoma in the CheckMate 358 trial. J Clin Oncol. 2020;38(22):2476-2487. doi:10.1200/JCO.20.00201.
6.
CoweyCLLiuFXKimR, et al.Real-world clinical outcomes with first-line avelumab in locally advanced/metastatic Merkel cell carcinoma in the USA: SPEAR-Merkel. Future Oncol. 2021;17(18):2339-2350. doi:10.2217/fon-2020-1250.
7.
NewJShentonLKsayerR, et al.Immune checkpoint inhibitors and vaccination: assessing safety, efficacy, and synergistic potential. Vaccines (Basel). 2024;12(11):1270. doi:10.3390/vaccines12111270.
8.
SahinUOehmPDerhovanessianE, et al.An RNA vaccine drives immunity in checkpoint-inhibitor-treated melanoma. Nature. 2020;585(7823):107-112. doi:10.1038/s41586-020-2537-9.
9.
BersanelliMVerzoniECortelliniA, et al.Impact of influenza vaccination on survival of patients with advanced cancer receiving immune checkpoint inhibitors (INVIDIa-2): final results of the multicentre, prospective, observational study. EClinicalMedicine. 2023;61:102044. doi:10.1016/j.eclinm.2023.102044.
10.
Kuri-CervantesLPampenaMBMengW, et al.Comprehensive mapping of immune perturbations associated with severe COVID-19. Sci Immunol. 2020;5(49):eabd7114. doi:10.1126/sciimmunol.abd7114.
11.
TanLWangQZhangD, et al.Lymphopenia predicts disease severity of COVID-19: a descriptive and predictive study. Signal Transduct Target Ther. 2020;5(1):33. doi:10.1038/s41392-020-0148-4.
12.
VanderbekeLVan MolPVan HerckY, et al.Monocyte-driven atypical cytokine storm and aberrant neutrophil activation as key mediators of COVID-19 disease severity. Nat Commun. 2021;12(1):4117. doi:10.1038/s41467-021-24360-w.
13.
GunaratneDAHowleJRVenessMJ. Definitive radiotherapy for Merkel cell carcinoma confers clinically meaningful in-field locoregional control: a review and analysis of the literature. J Am Acad Dermatol. 2017;77(1):142. doi:10.1016/j.jaad.2017.02.015.
14.
IyerJGParvathaneniUGooleyT, et al.Single-fraction radiation therapy in patients with metastatic Merkel cell carcinoma. Cancer Med. 2015;4(8):1161-1170. doi:10.1002/cam4.458.
15.
PostowMACallahanMKBarkerCA, et al.Immunologic correlates of the abscopal effect in a patient with melanoma. N Engl J Med. 2012;366(10):925-931. doi:10.1056/NEJMoa1112824.
16.
FormentiSCRudqvistNPGoldenE, et al.Radiotherapy induces responses of lung cancer to CTLA-4 blockade. Nat Med. 2018;24(12):1845-1851. doi:10.1038/s41591-018-0232-2.
17.
DemariaSColemanCNFormentiSC. Radiotherapy: changing the game in immunotherapy. Trends Cancer. 2016;2(6):286-294. doi:10.1016/j.trecan.2016.05.002.
BurnetteBCLiangHLeeY, et al.The efficacy of radiotherapy relies upon induction of type i interferon-dependent innate and adaptive immunity. Cancer Res. 2011;71(7):2488-2496. doi:10.1158/0008-5472.CAN-10-2820.
20.
ValachisARosenCKoliadiA, et al.Improved survival without increased toxicity with influenza vaccination in cancer patients treated with checkpoint inhibitors. Oncoimmunology. 2021;10(1):1886725. doi:10.1080/2162402X.2021.1886725.
21.
WeberJSCarlinoMSKhattakA, et al.Individualised neoantigen therapy mRNA-4157 (V940) plus pembrolizumab versus pembrolizumab monotherapy in resected melanoma (KEYNOTE-942): a randomised, phase 2b study. Lancet. 2024;403(10427):632-644. doi:10.1016/S0140-6736(23)02268-7.
22.
MassarelliEWilliamWJohnsonF, et al.Combining immune checkpoint blockade and tumor-specific vaccine for patients with incurable human papillomavirus 16-Related cancer: a phase 2 clinical trial. JAMA Oncol. 2019;5(1):67-73. doi:10.1001/jamaoncol.2018.4051.
