Rescue of Immunotherapy-Refractory Metastatic Merkel Cell Carcinoma With Conventionally Fractionated Radiotherapy and Concurrent Pembrolizumab
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 prom...
| Main Authors: | , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2019-04-01
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| Series: | Frontiers in Oncology |
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| Online Access: | https://www.frontiersin.org/article/10.3389/fonc.2019.00223/full |
| _version_ | 1828802456524423168 |
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| author | Brooke C. Bloom Alexander Augustyn Todd A. Pezzi Hari Menon Lauren L. Mayo Shalin J. Shah David L. Schwartz David L. Schwartz Steven J. Chmura Faye M. Johnson Faye M. Johnson James W. Welsh Stephen G. Chun |
| author_facet | Brooke C. Bloom Alexander Augustyn Todd A. Pezzi Hari Menon Lauren L. Mayo Shalin J. Shah David L. Schwartz David L. Schwartz Steven J. Chmura Faye M. Johnson Faye M. Johnson James W. Welsh Stephen G. Chun |
| author_sort | Brooke C. Bloom |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-12-12T07:04:22Z |
| format | Article |
| id | doaj.art-517414ba97be4b40bff6df40bf6ee72d |
| institution | Directory Open Access Journal |
| issn | 2234-943X |
| language | English |
| last_indexed | 2024-12-12T07:04:22Z |
| publishDate | 2019-04-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Oncology |
| spelling | doaj.art-517414ba97be4b40bff6df40bf6ee72d2022-12-22T00:33:46ZengFrontiers Media S.A.Frontiers in Oncology2234-943X2019-04-01910.3389/fonc.2019.00223439074Rescue of Immunotherapy-Refractory Metastatic Merkel Cell Carcinoma With Conventionally Fractionated Radiotherapy and Concurrent PembrolizumabBrooke C. Bloom0Alexander Augustyn1Todd A. Pezzi2Hari Menon3Lauren L. Mayo4Shalin J. Shah5David L. Schwartz6David L. Schwartz7Steven J. Chmura8Faye M. Johnson9Faye M. Johnson10James W. Welsh11Stephen G. Chun12Trinity University, San Antonio, TX, United StatesDepartment of Radiation Oncology, The University of Texas, MD Anderson Cancer Center, Houston, TX, United StatesDepartment of Radiation Oncology, The University of Texas, MD Anderson Cancer Center, Houston, TX, United StatesDepartment of Radiation Oncology, The University of Texas, MD Anderson Cancer Center, Houston, TX, United StatesDepartment of Radiation Oncology, The University of Texas, MD Anderson Cancer Center, Houston, TX, United StatesDepartment of Radiation Oncology, The University of Texas, MD Anderson Cancer Center, Houston, TX, United StatesDepartment of Radiation Oncology, The University of Texas, MD Anderson Cancer Center, Houston, TX, United StatesDepartment of Radiation Oncology, University of Tennessee Health Science Center, Memphis, TN, United StatesDepartment of Radiation and Cellular Oncology, University of Chicago, Chicago, IL, United StatesDivision of Cancer Medicine, Department of Thoracic, Head and Neck Medical Oncology, The University of Texas, MD Anderson Cancer Center, Houston, TX, United StatesThe University of Texas Graduate School of Biomedical Sciences, Houston, TX, United StatesDepartment of Radiation Oncology, The University of Texas, MD Anderson Cancer Center, Houston, TX, United StatesDepartment of Radiation Oncology, The University of Texas, MD Anderson Cancer Center, Houston, TX, United StatesMerkel 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.https://www.frontiersin.org/article/10.3389/fonc.2019.00223/fullMerkel cell carcinomaradiationabscopalPD-1PD-L1immunotherapy |
| spellingShingle | Brooke C. Bloom Alexander Augustyn Todd A. Pezzi Hari Menon Lauren L. Mayo Shalin J. Shah David L. Schwartz David L. Schwartz Steven J. Chmura Faye M. Johnson Faye M. Johnson James W. Welsh Stephen G. Chun Rescue of Immunotherapy-Refractory Metastatic Merkel Cell Carcinoma With Conventionally Fractionated Radiotherapy and Concurrent Pembrolizumab Frontiers in Oncology Merkel cell carcinoma radiation abscopal PD-1 PD-L1 immunotherapy |
| title | Rescue of Immunotherapy-Refractory Metastatic Merkel Cell Carcinoma With Conventionally Fractionated Radiotherapy and Concurrent Pembrolizumab |
| title_full | Rescue of Immunotherapy-Refractory Metastatic Merkel Cell Carcinoma With Conventionally Fractionated Radiotherapy and Concurrent Pembrolizumab |
| title_fullStr | Rescue of Immunotherapy-Refractory Metastatic Merkel Cell Carcinoma With Conventionally Fractionated Radiotherapy and Concurrent Pembrolizumab |
| title_full_unstemmed | Rescue of Immunotherapy-Refractory Metastatic Merkel Cell Carcinoma With Conventionally Fractionated Radiotherapy and Concurrent Pembrolizumab |
| title_short | Rescue of Immunotherapy-Refractory Metastatic Merkel Cell Carcinoma With Conventionally Fractionated Radiotherapy and Concurrent Pembrolizumab |
| title_sort | rescue of immunotherapy refractory metastatic merkel cell carcinoma with conventionally fractionated radiotherapy and concurrent pembrolizumab |
| topic | Merkel cell carcinoma radiation abscopal PD-1 PD-L1 immunotherapy |
| url | https://www.frontiersin.org/article/10.3389/fonc.2019.00223/full |
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