Clinical and immunologic correlates of response to PD-1 blockade in a patient with metastatic renal medullary carcinoma
Background Renal medullary carcinoma (RMC) is a rare kidney tumor that occurs in adolescent and young adults, typically in association with sickle cell trait. RMC exhibits rapid disease progression, frequent metastases at diagnosis, and dismal clinical outcomes. Currently available therapies, includ...
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BMJ Publishing Group
2017-08-01
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| Series: | Journal for ImmunoTherapy of Cancer |
| Online Access: | https://jitc.bmj.com/content/5/1/1.full |
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| author | Igor Puzanov Douglas B. Johnson Kathryn E. Beckermann Pradeep C. Jolly Ju Y. Kim Jennifer Bordeaux W. Kimryn Rathmell |
| author_facet | Igor Puzanov Douglas B. Johnson Kathryn E. Beckermann Pradeep C. Jolly Ju Y. Kim Jennifer Bordeaux W. Kimryn Rathmell |
| author_sort | Igor Puzanov |
| collection | DOAJ |
| description | Background Renal medullary carcinoma (RMC) is a rare kidney tumor that occurs in adolescent and young adults, typically in association with sickle cell trait. RMC exhibits rapid disease progression, frequent metastases at diagnosis, and dismal clinical outcomes. Currently available therapies, including cisplatin-based combination chemotherapy, multi-tyrosine kinase, and mTOR inhibitor strategies demonstrate either transient responses or minimal activity. Therefore, further molecular characterization and additional treatment strategies are urgently needed in this aggressive disease. The role of immune system surveillance and responsiveness to anti-PD-1 therapies in RMC are completely unexplored.Case presentation A 29 year old male with sickle cell trait presented with painless hematuria that ultimately resulted in a diagnosis of RMC. He underwent total nephrectomy and adjuvant cytotoxic chemotherapy with carboplatin, gemcitabine, paclitaxel, and bevacizumab. As is common in this aggressive form of kidney cancer he recurred with biopsy proven lymph node metastasis. He was started on checkpoint inhibitor therapy with nivolumab that inhibits program cell death protein 1 (PD-1), and on his first follow-up imaging he was found to have a partial response that on subsequent scans ultimately resulted in a complete response lasting greater than nine months. In this report, we present a patient with metastatic RMC who exhibited a clinical response to nivolumab, as well as the genetic and immunologic correlates of the pre-treatment tumor. Provocatively, robust immune infiltrate and expression of immune checkpoints were observed, despite the presence of a low mutation burden.Conclusions Here, we report the first case of immune microenvironment profiling and response to anti-PD-1 in a patient with RMC to our knowledge. This case suggests that anti-PD-1 based therapies may have clinical activity in RMC. |
| format | Article |
| id | doaj-art-88b1bca2320d4aa9b83bcaa9d87b6fd3 |
| institution | DOAJ |
| issn | 2051-1426 |
| language | English |
| publishDate | 2017-08-01 |
| publisher | BMJ Publishing Group |
| record_format | Article |
| series | Journal for ImmunoTherapy of Cancer |
| spelling | doaj-art-88b1bca2320d4aa9b83bcaa9d87b6fd32025-08-20T03:11:52ZengBMJ Publishing GroupJournal for ImmunoTherapy of Cancer2051-14262017-08-015110.1186/s40425-016-0206-1Clinical and immunologic correlates of response to PD-1 blockade in a patient with metastatic renal medullary carcinomaIgor Puzanov0Douglas B. Johnson1Kathryn E. Beckermann2Pradeep C. Jolly3Ju Y. Kim4Jennifer Bordeaux5W. Kimryn Rathmell65Roswell Park Comprehensive Cancer Center, Buffalo, NY, USAAff1 grid.412807.80000000419369916Department of Medicine, Division of Hematology/OncologyVanderbilt University Medical Center 37232 Nashville TN USAAff1 grid.412807.80000000419369916Department of Medicine, Division of Hematology/OncologyVanderbilt University Medical Center 37232 Nashville TN USAAff2 grid.477314.20000000404313979Georgia Cancer Specialists 30342 Atlanta GA USAAff3 Genoptix Inc 92008 Carlsbad CA USA4Navigate BioPharma Services, Inc., Carlsbad, CA, USAAff1 grid.412807.80000000419369916Department of Medicine, Division of Hematology/OncologyVanderbilt University Medical Center 37232 Nashville TN USABackground Renal medullary carcinoma (RMC) is a rare kidney tumor that occurs in adolescent and young adults, typically in association with sickle cell trait. RMC exhibits rapid disease progression, frequent metastases at diagnosis, and dismal clinical outcomes. Currently available therapies, including cisplatin-based combination chemotherapy, multi-tyrosine kinase, and mTOR inhibitor strategies demonstrate either transient responses or minimal activity. Therefore, further molecular characterization and additional treatment strategies are urgently needed in this aggressive disease. The role of immune system surveillance and responsiveness to anti-PD-1 therapies in RMC are completely unexplored.Case presentation A 29 year old male with sickle cell trait presented with painless hematuria that ultimately resulted in a diagnosis of RMC. He underwent total nephrectomy and adjuvant cytotoxic chemotherapy with carboplatin, gemcitabine, paclitaxel, and bevacizumab. As is common in this aggressive form of kidney cancer he recurred with biopsy proven lymph node metastasis. He was started on checkpoint inhibitor therapy with nivolumab that inhibits program cell death protein 1 (PD-1), and on his first follow-up imaging he was found to have a partial response that on subsequent scans ultimately resulted in a complete response lasting greater than nine months. In this report, we present a patient with metastatic RMC who exhibited a clinical response to nivolumab, as well as the genetic and immunologic correlates of the pre-treatment tumor. Provocatively, robust immune infiltrate and expression of immune checkpoints were observed, despite the presence of a low mutation burden.Conclusions Here, we report the first case of immune microenvironment profiling and response to anti-PD-1 in a patient with RMC to our knowledge. This case suggests that anti-PD-1 based therapies may have clinical activity in RMC.https://jitc.bmj.com/content/5/1/1.full |
| spellingShingle | Igor Puzanov Douglas B. Johnson Kathryn E. Beckermann Pradeep C. Jolly Ju Y. Kim Jennifer Bordeaux W. Kimryn Rathmell Clinical and immunologic correlates of response to PD-1 blockade in a patient with metastatic renal medullary carcinoma Journal for ImmunoTherapy of Cancer |
| title | Clinical and immunologic correlates of response to PD-1 blockade in a patient with metastatic renal medullary carcinoma |
| title_full | Clinical and immunologic correlates of response to PD-1 blockade in a patient with metastatic renal medullary carcinoma |
| title_fullStr | Clinical and immunologic correlates of response to PD-1 blockade in a patient with metastatic renal medullary carcinoma |
| title_full_unstemmed | Clinical and immunologic correlates of response to PD-1 blockade in a patient with metastatic renal medullary carcinoma |
| title_short | Clinical and immunologic correlates of response to PD-1 blockade in a patient with metastatic renal medullary carcinoma |
| title_sort | clinical and immunologic correlates of response to pd 1 blockade in a patient with metastatic renal medullary carcinoma |
| url | https://jitc.bmj.com/content/5/1/1.full |
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