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PRaG regimens for rechallenge in a patient with acquired resistance to PD-1 inhibitor in advanced refractory renal pelvis carcinoma: A case report
Zhihui Hong1,2,3† ,
Hong Xu4,5† ,
Yuehong Kong5,6,7 ,
Meiling Xu5,6,7 ,
Yifu Ma5,6,7 ,
Pengfei Xing5,6,7* ,
Liyuan Zhang5,6,7*
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1
Department of Nuclear Medicine, The Second Affiliated Hospital of Soochow University, Suzhou, 215005 Jiangsu,
China
2
State Key Laboratory of Radiation Medicine and Protection, Soochow University, Suzhou, 215123, Jiangsu,
China
3
INHC Key Laboratory of Nuclear Medicine and Jiangsu Key Laboratory of Molecular Nuclear Medicine, Wuxi, 214063, Jiangsu,
China
4
Department of Oncology, Changshu Hospital Affiliated to Soochow University, Suzhou, 215488 Jiangsu,
China
5
Department of Radiotherapy and Oncology, The Second Affiliated Hospital of Soochow University, Suzhou, 215005 Jiangsu,
China
6
Institution of Radiotherapy and Oncology, Soochow University, Suzhou, 215123 Jiangsu,
China
7
Laboratory for Combined Radiotherapy and Immunotherapy of Cancer, The Second Affiliated Hospital of Soochow University, Suzhou, 215005 Jiangsu,
China
Submitted: 13 April 2023 | Accepted: 29 June 2023 | Published: 12 July 2023
© 2023 by the Author(s). This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution 4.0 International License ( https://creativecommons.org/licenses/by/4.0/ )
Abstract
Despite the burgeoning popularity of programmed death-1 (PD-1) inhibitors in cancer treatment, it is not uncommon for patients who initially respond to this therapy to experience relapse over time. Here, we present the case of a patient with advanced renal pelvis carcinoma who had received prior treatment with chemotherapy and PD-1 inhibitor therapy but ultimately experienced disease progression. Subsequently, the patient underwent a combination therapy known as PRaG 2.0, which included PD-1 inhibitor, radiotherapy, granulocyte-macrophage colony-stimulating factor, and interleukin-2, resulting in effective disease control without significant adverse events. The duration of disease control lasted for a period of 10 months.
Keywords
PD-1 inhibitor
Radiotherapy
PRaG therapy
Rechallenge
Renal pelvis carcinoma
Funding
National Natural Science Foundation of China
Key R&D Programme of Jiangsu Province
Suzhou Radiotherapy Clinical Medical Center
Open Project of the State Key Laboratory of Radiology and Radiation Protection of Soochow University
Open Project of Provincial Key Laboratory of Soochow University
Subject construction support project of the Second Affiliated Hospital of Soochow University
Suzhou Science and Technology Development Plan
Chinese Society of Clinical Oncology Research Foundation of Beijing
Wu Jieping Medical Foundation
Special project of “Technological Innovation” project of CNNC Medical Industry Co. Ltd
Suzhou Science and Education Health Project
Postgraduate Research & Practice Innovation Program of Jiangsu Province
Suzhou Key Laboratory for Combined Radiotherapy and Immunotherapy of Cancer
Suzhou Clinical Key Diseases Diagnosis and Treatment Technology Special Project
Csco fund
2021 “Nuclear Medicine Technology Innovation” Project of CNNC Medical
Research project of China Baoyuan Investment Co., Ltd.
Project of State Key Laboratory of Radiation Medicine and Protection, Soochow University
Subject construction support project of the Second Affiliated Hospital of Soochow University
Open Program of NHC Key Laboratory of Nuclear Medicine and Jiangsu Key Laboratory of Molecular Nuclear Medicine
Conflict of interest
The authors declare they have no competing interests.
References
- Wu Y, Mou H, 2020, Complete remission in a patient with advanced renal pelvis carcinoma with lung metastasis treated with durvalumab immunotherapy: A case report. Ann Palliat Med, 9: 2408–2413. https://doi.org/10.21037/apm-20-1338
- Farina MS, Lundgren KT, Bellmunt J, 2017, Immunotherapy in urothelial cancer: Recent results and future perspectives. Drugs, 77: 1077–1089. https://doi.org/10.1007/s40265-017-0748-7
- Lan J, Li R, Yin LM, et al., 2018, Targeting myeloid-derived suppressor cells and programmed death ligand 1 confers therapeutic advantage of ablative hypofractionated radiation therapy compared with conventional fractionated radiation therapy. Int J Radiat Oncol Biol Phys, 101: 74–87. https://doi.org/10.1016/j.ijrobp.2018.01.071
- Vanpouille-Box C, Pilones KA, Wennerberg E, et al., 2015, In situ vaccination by radiotherapy to improve responses to anti-CTLA-4 treatment. Vaccine, 33: 7415–7422. https://doi.org/10.1016/j.vaccine.2015.05.105
- Bernstein MB, Krishnan S, Hodge JW, et al., 2016, Immunotherapy and stereotactic ablative radiotherapy (ISABR): A curative approach? Nat Rev Clin Oncol, 13: 516– 524. https://doi.org/10.1038/nrclinonc.2016.30
- Birtle A, Johnson M, Chester J, et al., 2020, Adjuvant chemotherapy in upper tract urothelial carcinoma (the POUT trial): A phase 3, open-label, randomised controlled trial. Lancet, 395: 1268–1277. https://doi.org/10.1016/S0140-6736(20)30415-3
- Roupret M, Babjuk M, Burger M, et al., 2021, European association of urology guidelines on upper urinary tract urothelial carcinoma: 2020 update. Eur Urol, 79: 62–79. https://doi.org/10.1016/j.eururo.2020.05.042
- Witjes JA, Bruins HM, Cathomas R, et al., 2021, European association of urology guidelines on muscle-invasive and metastatic bladder cancer: Summary of the 2020 guidelines. Eur Urol, 79: 82–104. https://doi.org/10.1016/j.eururo.2020.03.055
- Fujita K, Yamamoto Y, Kanai O, et al., 2020, Retreatment with anti-PD-1 antibody in non-small cell lung cancer patients previously treated with anti-PD-L1 antibody. Thorac Cancer, 11: 15–18. https://doi.org/10.1111/1759-7714.13241
- Martini DJ, Lalani AA, Bosse D, et al., 2017, Response to single agent PD-1 inhibitor after progression on previous PD-1/PD-L1 inhibitors: A case series. J Immunother Cancer, 5: 66. https://doi.org/10.1186/s40425-017-0273-y
- Fujita K, Uchida N, Yamamoto Y, et al., 2019, Retreatment with anti-PD-L1 antibody in advanced non-small cell lung cancer previously treated with anti-PD-1 antibodies. Anticancer Res, 39: 3917–3921. https://doi.org/10.21873/anticanres.13543
- Fujita K, Uchida N, Kanai O, et al., 2018, Retreatment with pembrolizumab in advanced non-small cell lung cancer patients previously treated with nivolumab: Emerging reports of 12 cases. Cancer Chemother Pharmacol, 81: 1105– 1109. https://doi.org/10.1007/s00280-018-3585-9
- Hakozaki T, Okuma Y, Kashima J, 2018, Re-challenging immune checkpoint inhibitor in a patient with advanced non-small cell lung cancer: A case report. BMC Cancer, 18: 302. https://doi.org/10.1186/s12885-018-4212-1
- Leighl NB, Redman MW, Rizvi N, et al., 2021, Phase II study of durvalumab plus tremelimumab as therapy for patients with previously treated anti-PD-1/PD-L1 resistant stage IV squamous cell lung cancer (Lung-MAP substudy S1400F, NCT03373760). J Immunother Cancer, 9: e002973. https://doi.org/10.1136/jitc-2021-002973
- Asna N, Livoff A, Batash R, et al., 2018, Radiation therapy and immunotherapy-a potential combination in cancer treatment. Curr Oncol, 25: e454–e460. https://doi.org/10.3747/co.25.4002
- Dovedi SJ, Adlard AL, Lipowska-Bhalla G, et al., 2014, Acquired resistance to fractionated radiotherapy can be overcome by concurrent PD-L1 blockade. Cancer Res, 74: 5458–5468. https://doi.org/10.1158/0008-5472.can-14-1258
- Theelen WS, Peulen HM, Lalezari F, et al., 2019, Effect of pembrolizumab after stereotactic body radiotherapy vs pembrolizumab alone on tumor response in patients with advanced non-small cell lung cancer: Results of the PEMBRO-RT phase 2 randomized clinical trial. JAMA Oncol, 5: 1276–1282. https://doi.org/10.1001/jamaoncol.2019.1478
- Kelley RK, Mitchell E, Behr S, et al., 2018, Phase II trial of pembrolizumab (PEM) plus granulocyte macrophage colony stimulating factor (GM-CSF) in advanced biliary cancers (ABC). J Clin Oncol, 36: 386. https://doi.org/10.1200/jco.2018.36.4_suppl.386
- Zhao X, Kong Y, Zhang L, 2020, Anti-PD-1 immunotherapy combined with stereotactic body radiation therapy and GM-CSF as salvage therapy in a PD-L1-negative patient with refractory metastatic esophageal squamous cell carcinoma: A case report and literature review. Front Oncol, 10: 1625. https://doi.org/10.3389/fonc.2020.01625
- Smith KA, 1988, Interleukin-2: Inception, impact, and implications. Science, 240: 1169–1176. https://doi.org/10.1126/science.3131876
- Rochman Y, Spolski R, Leonard WJ, 2009, New insights into the regulation of T cells by gamma(c) family cytokines. Nat Rev Immunol, 9: 480I490. https://doi.org/10.1038/nri2580