Predictive role of PD-L1 expression in the response of renal Medullary carcinoma to PD-1 inhibition

J Immunother Cancer. 2017 Aug 15;5(1):62. doi: 10.1186/s40425-017-0267-9.

Abstract

Background: Renal medullary carcinoma is one of the rarest malignancies arising from the kidney. Despite various aggressive therapeutic regimens, mortality remains significantly high (95%) with a median overall survival of 5 months. Furthermore, the scarcity of this malignancy renders randomized clinical trials impossible. We examined the expression of programmed death ligand 1 (PD-L1) in two new renal medullary carcinoma cases, investigated their responses to the PD-L1 inhibitor nivolumab and explored the predictive role of the rate of PD-L1 expression in such response.

Case presentation: Two African-American patients (male and female) with sickle cell trait who presented to our center with hematuria and flank pain were diagnosed with metastatic renal medullary carcinoma. PD-L1 was expressed at rate of 25% and 60% in patient 1 and 2 respectively. Following nephrectomy, they were started on nivolumab. Patient 1 initially responded to the treatment with regression of metastatic lesions. However, following this early response, patient 1 who has been receiving nivolumab for more than 15 months, was noted to have a disease progression. Patient 2 had disease progression after 3 months of nivolumab therapy.

Conclusions: Although PD-L1 is expressed in these patients with renal medullary carcinoma, response to nivolumab was only observed in patient 1 whose tumor has the lowest rate of PD-L1 expression. This may suggest that in RMC, response to PD-L1 inhibition therapy may not correlate with the rate of PD-L1 expression.

Keywords: Immunotherapy; Nivolumab; Pd-L1; Renal medullary carcinoma; Sickle cell trait.

Publication types

  • Case Reports

MeSH terms

  • Antibodies, Monoclonal / administration & dosage*
  • Antibodies, Monoclonal / therapeutic use
  • B7-H1 Antigen / metabolism*
  • Carcinoma, Medullary / drug therapy*
  • Carcinoma, Medullary / metabolism
  • Disease Progression
  • Female
  • Gene Expression Regulation, Neoplastic
  • Humans
  • Kidney Neoplasms / drug therapy*
  • Kidney Neoplasms / metabolism
  • Male
  • Middle Aged
  • Nivolumab
  • Treatment Outcome
  • Young Adult

Substances

  • Antibodies, Monoclonal
  • B7-H1 Antigen
  • CD274 protein, human
  • Nivolumab