Rescue of Immunotherapy-Refractory Metastatic Merkel Cell Carcinoma With Conventionally Fractionated Radiotherapy and Concurrent Pembrolizumab
- PMID: 31024834
- PMCID: PMC6459944
- DOI: 10.3389/fonc.2019.00223
Rescue of Immunotherapy-Refractory Metastatic Merkel Cell Carcinoma With Conventionally Fractionated Radiotherapy and Concurrent Pembrolizumab
Abstract
Merkel cell carcinoma has historically had dismal prognosis with limited cytotoxic chemotherapy options that provide durable control of metastatic disease. The advent of anti-programmed death protein (anti-PD1)/anti-programmed death-ligand 1 (anti-PD-L1) directed immunotherapy has shown initial promise in Merkel cell carcinoma and radiation might augment immune responses. We present a case report of a 70-year-old male who underwent resection of Merkel cell carcinoma of the right thigh with a close margin and positive right inguinal involvement. Due to high-risk features, the patient was treated with adjuvant radiation to the right groin and with systemic carboplatin/etoposide, but developed local failure requiring salvage surgical resection. The patient then developed metastatic disease with biopsy proven retroperitoneal involvement refractory to doxorubicin/cyclophosphamide chemotherapy. The patient was then transitioned to single-agent pembrolizumab with a partial response for 10 months until developing progressive disease involving the left inguinal and left external iliac nodal regions. The progressive left inguinal/pelvic disease was treated with conventionally fractionated intensity modulated radiation therapy to a dose of 45 Gy delivered in 25 fractions. Following radiation therapy, the patient had complete response of all sites of disease throughout the body on imaging by RECIST criteria including retroperitoneal and mediastinal disease outside the radiation field. At 20 months post-radiation, the patient remains on pembrolizumab without evidence of disease on imaging. Herein, we present a case of durable response of metastatic Merkel cell carcinoma treated with concurrent radiation and pembrolizumab, providing evidence that radiation might improve systemic responses to anti-PD1/PD-L1 directed immune therapy. Ongoing prospective trials evaluating the utility of radiation in conjunction with immunotherapy for Merkel cell carcinoma are anticipated to provide clarity on the frequency and durability of abscopal responses when radiation is combined with immune checkpoint inhibitors.
Keywords: Merkel cell carcinoma; PD-1; PD-L1; abscopal; checkpoint; immunotherapy; radiation.
Figures
![Figure 1](https://cdn.statically.io/img/www.ncbi.nlm.nih.gov/pmc/articles/instance/6459944/bin/fonc-09-00223-g0001.gif)
![Figure 2](https://cdn.statically.io/img/www.ncbi.nlm.nih.gov/pmc/articles/instance/6459944/bin/fonc-09-00223-g0002.gif)
![Figure 3](https://cdn.statically.io/img/www.ncbi.nlm.nih.gov/pmc/articles/instance/6459944/bin/fonc-09-00223-g0003.gif)
![Figure 4](https://cdn.statically.io/img/www.ncbi.nlm.nih.gov/pmc/articles/instance/6459944/bin/fonc-09-00223-g0004.gif)
![Figure 5](https://cdn.statically.io/img/www.ncbi.nlm.nih.gov/pmc/articles/instance/6459944/bin/fonc-09-00223-g0005.gif)
Similar articles
-
Avelumab in patients with chemotherapy-refractory metastatic Merkel cell carcinoma: a multicentre, single-group, open-label, phase 2 trial.Lancet Oncol. 2016 Oct;17(10):1374-1385. doi: 10.1016/S1470-2045(16)30364-3. Epub 2016 Sep 1. Lancet Oncol. 2016. PMID: 27592805 Free PMC article. Clinical Trial.
-
In-field and abscopal response after short-course radiation therapy in patients with metastatic Merkel cell carcinoma progressing on PD-1 checkpoint blockade: a case series.J Immunother Cancer. 2018 May 30;6(1):43. doi: 10.1186/s40425-018-0352-8. J Immunother Cancer. 2018. PMID: 29848371 Free PMC article.
-
Does Neutron Radiation Therapy Potentiate an Immune Response to Merkel Cell Carcinoma?Int J Part Ther. 2018 Summer;5(1):183-195. doi: 10.14338/IJPT-18-00012.1. Epub 2018 Sep 21. Int J Part Ther. 2018. PMID: 31773029 Free PMC article.
-
[Immune checkpoint inhibition in Merkel cell carcinoma].Hautarzt. 2019 Sep;70(9):684-690. doi: 10.1007/s00105-019-4465-x. Hautarzt. 2019. PMID: 31468071 Review. German.
-
Immunotherapy for Merkel Cell Carcinoma.Curr Treat Options Oncol. 2018 Sep 20;19(11):57. doi: 10.1007/s11864-018-0574-5. Curr Treat Options Oncol. 2018. PMID: 30238195 Review.
Cited by
-
Increased risk of recurrence and disease-specific death following delayed postoperative radiation for Merkel cell carcinoma.J Am Acad Dermatol. 2024 Feb;90(2):261-268. doi: 10.1016/j.jaad.2023.07.1047. Epub 2023 Sep 30. J Am Acad Dermatol. 2024. PMID: 37778663 Free PMC article.
-
Introducing Radiotherapy in Metastatic Merkel Cell Carcinoma Patients with Limited Progression on Avelumab: An Effective Step against Primary and Secondary Immune Resistance?J Pers Med. 2023 May 17;13(5):841. doi: 10.3390/jpm13050841. J Pers Med. 2023. PMID: 37241012 Free PMC article.
-
The role of radiotherapy in the updated German S2k guideline for management of Merkel cell carcinoma.Strahlenther Onkol. 2023 May;199(5):433-435. doi: 10.1007/s00066-023-02068-8. Epub 2023 Mar 28. Strahlenther Onkol. 2023. PMID: 36976298 Free PMC article.
-
Short-Interval, Low-Dose Peptide Receptor Radionuclide Therapy in Combination with PD-1 Checkpoint Immunotherapy Induces Remission in Immunocompromised Patients with Metastatic Merkel Cell Carcinoma.Pharmaceutics. 2022 Jul 14;14(7):1466. doi: 10.3390/pharmaceutics14071466. Pharmaceutics. 2022. PMID: 35890361 Free PMC article.
-
The Treatment for a Patient with Cancer of Unknown Primary: A Case Report.Dose Response. 2021 Nov 21;19(4):15593258211056185. doi: 10.1177/15593258211056185. eCollection 2021 Oct-Dec. Dose Response. 2021. PMID: 34887715 Free PMC article.
References
Publication types
LinkOut - more resources
Full Text Sources
Other Literature Sources
Research Materials