Pseudoprogression manifesting as recurrent ascites with anti-PD-1 immunotherapy in urothelial bladder cancer

J Immunother Cancer. 2018 Apr 4;6(1):24. doi: 10.1186/s40425-018-0334-x.

Abstract

Background: Immunotherapies targeting the PD-1 checkpoint pathway have recently gained regulatory approval in numerous cancer types. With the widespread use of immune checkpoint therapies, varying patterns of responses and immune-related adverse events are being observed.

Case presentation: In this case, we highlight a patient who developed recurrent, large-volume ascites, while simultaneously having a 49% reduction in peritoneal tumor lesion size by RECIST criteria. Sampling of the fluid revealed high levels of IL-6 and IL-15. Cytology revealed no malignant cells on 4 separate paracenteses over a period of 6 weeks. Cell counts revealed that 45% of cells were lymphocytes, and further analysis was performed by fluorescence-activated cell sorting (FACS). The majority of lymphocytes were CD8+, of which 78% were PD-1+ and 43% were HLA-DR+ indicating an activated phenotype.

Conclusions: In summary, treatment with anti-PD-1 therapy may result in pseudoprogression manifested by ascitic fluid accumulation due to the influx of activated T cells. Since worsening of ascites is typically associated with disease progression, it is important to consider the possibility of pesudoprogression in such patients undergoing therapy with immune checkpoint inhibitors.

Keywords: Bladder urothelial cancer; Immune checkpoint; Immunotherapy; PD-1; Pembrolizumab; Pseudoprogression.

Publication types

  • Case Reports
  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antibodies, Monoclonal, Humanized / therapeutic use*
  • Antineoplastic Agents, Immunological / therapeutic use*
  • Ascites / chemically induced*
  • Ascites / diagnostic imaging
  • Ascites / immunology
  • CD8-Positive T-Lymphocytes / drug effects
  • CD8-Positive T-Lymphocytes / immunology
  • Disease Progression
  • Female
  • Humans
  • Immunotherapy
  • Middle Aged
  • Positron Emission Tomography Computed Tomography
  • Programmed Cell Death 1 Receptor / antagonists & inhibitors*
  • Recurrence
  • Urinary Bladder Neoplasms / diagnostic imaging
  • Urinary Bladder Neoplasms / drug therapy*
  • Urinary Bladder Neoplasms / immunology

Substances

  • Antibodies, Monoclonal, Humanized
  • Antineoplastic Agents, Immunological
  • PDCD1 protein, human
  • Programmed Cell Death 1 Receptor
  • pembrolizumab