title: Clinical and immunologic correlates of response to PD-1 blockade in a patient with metastatic renal medullary carcinoma.
abstract: 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.
  
  
  
  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.
  
  
  
  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.
authors.affiliation: Department of Medicine, Division of Hematology/Oncology, Vanderbilt University Medical Center, Nashville, TN 37232 USA.
authors.forename: Kathryn E
authors.initials: KE
authors.lastname: Beckermann
authors.affiliation: Georgia Cancer Specialists, Atlanta, GA 30342 USA.
authors.forename: Pradeep C
authors.initials: PC
authors.lastname: Jolly
authors.affiliation: Genoptix Inc, Carlsbad, CA 92008 USA.
authors.forename: Ju Y
authors.initials: JY
authors.lastname: Kim
authors.affiliation: Genoptix Inc, Carlsbad, CA 92008 USA.
authors.forename: Jennifer
authors.initials: J
authors.lastname: Bordeaux
authors.affiliation: Roswell Park Cancer Institute, Buffalo, NY 14263 USA.
authors.forename: Igor
authors.initials: I
authors.lastname: Puzanov
authors.affiliation: Department of Medicine, Division of Hematology/Oncology, Vanderbilt University Medical Center, Nashville, TN 37232 USA ; Vanderbilt-Ingram Cancer Center, 777 Preston Research Building, 2220 Pierce Avenue, Nashville, TN 37232 USA.
authors.forename: W Kimryn
authors.initials: WK
authors.lastname: Rathmell
authors.affiliation: Department of Medicine, Division of Hematology/Oncology, Vanderbilt University Medical Center, Nashville, TN 37232 USA ; Vanderbilt-Ingram Cancer Center, 777 Preston Research Building, 2220 Pierce Avenue, Nashville, TN 37232 USA.
authors.forename: Douglas B
authors.initials: DB
authors.lastname: Johnson
mesh_terms: D000328:Adult; D000911:Antibodies, Monoclonal / Q000008:administration & dosage; D018276:Carcinoma, Medullary / Q000235:genetics / Q000276:immunology / Q000473:pathology / Q000628:therapy*; D005260:Female; D006801:Humans; D007680:Kidney Neoplasms / Q000235:genetics / Q000276:immunology / Q000628:therapy*; D008297:Male; D009362:Neoplasm Metastasis; D000077594:Nivolumab; D061026:Programmed Cell Death 1 Receptor / Q000037:antagonists & inhibitors / Q000235:genetics / Q000276:immunology*; D059016:Tumor Microenvironment / Q000187:drug effects* / Q000276:immunology
chemical_list: D000911:Antibodies, Monoclonal; C105992:PDCD1 protein, human; D061026:Programmed Cell Death 1 Receptor; D000077594:Nivolumab
keywords: Nivolumab; PD-1; Renal cell carcinoma; Renal medullary carcinoma