Current challenges of hematologic complications due to immune checkpoint blockade: a comprehensive review

Ann Hematol. 2022 Jan;101(1):1-10. doi: 10.1007/s00277-021-04690-x. Epub 2021 Dec 28.

Abstract

Immune checkpoint blockade has demonstrated durable clinical benefits in a variety of malignancies. These immune checkpoint inhibitors (ICIs) produce unwanted autoimmune reactions due to an impaired self-tolerance. Hematologic immune-related adverse events (heme-irAEs) have been increasingly reported in the literature with a reported fatality rate of 12%. In this review, we illustrate 3 cases treated at Johns Hopkins Hospital for ICI-induced agranulocytosis, aplastic anemia, and thrombocytopenia. We then summarize the available evidence regarding the incidence and prevalence of heme-irAEs. We identified immune thrombocytopenia and hemolytic anemia as the most commonly reported heme-irAEs which are more commonly observed with nivolumab therapy. Median time to onset of heme-irAEs varies between patients but occurs earlier with CTLA-4 inhibitors than with anti-PD-L1/PD-1 agents. We also describe the current challenges regarding the recurrence of heme-irAEs despite immune checkpoint blockade termination. We provide the available evidence supporting a mixed T-cell and B-cell immune-mediated response. Finally, we review the treatment algorithm of these complications and provide treatment alternatives to steroid-refractory cases.

Keywords: Hematologic complications; Immune checkpoint blockade; Immunotherapy; Steroid-refractory; Toxicity.

Publication types

  • Case Reports
  • Review

MeSH terms

  • Aged
  • Agranulocytosis / chemically induced*
  • Agranulocytosis / therapy
  • Anemia, Aplastic / chemically induced*
  • Anemia, Aplastic / therapy
  • Anemia, Hemolytic / chemically induced*
  • Anemia, Hemolytic / therapy
  • Disease Management
  • Female
  • Humans
  • Immune Checkpoint Inhibitors / adverse effects*
  • Immune Checkpoint Inhibitors / therapeutic use
  • Male
  • Middle Aged
  • Neoplasms / drug therapy
  • Purpura, Thrombocytopenic, Idiopathic / chemically induced*
  • Purpura, Thrombocytopenic, Idiopathic / therapy

Substances

  • Immune Checkpoint Inhibitors