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

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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.

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Authors and Affiliations

  1. Department of Medical Oncology, Johns Hopkins University, Baltimore, MD, USA

    Paola Ghanem

  2. Johns Hopkins Kimmel Cancer Center, Baltimore, MD, USA

    Kristen Marrone & Julie R. Brahmer

  3. Cancer Specialists of North Florida, Fleming Island, FL, USA

    Satish Shanbhag

  4. Division of Hematology, Department of Medicine, The Johns Hopkins University, 1830 E. Monument Street, Suite 7300, Baltimore, MD, 21205, USA

    Satish Shanbhag & Rakhi P. Naik

Authors
  1. Paola Ghanem
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  2. Kristen Marrone
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  4. Julie R. Brahmer
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Contributions

All authors contributed to the study. Literature search and data extraction were performed by Paola Ghanem. The draft of the manuscript was written by Paola Ghanem and all authors critically revised the previous versions of the manuscript. All authors read and approved the final manuscript.

Corresponding author

Correspondence to Rakhi P. Naik.

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Conflict of interest

Paola Ghanem has no financial or non-financial interests to disclose. Satish Shanbhag has received consulting fees from Takeda oncology, GSK, Daiichi-Sankyo, Kura oncology, Celgene, Beigene, and institutional research grant support from Daiichi Sankyo. Kristen Marrone consulted and was part of the advisory boards for AstraZeneca and Amgen. Julie R. Brahmer is a consultant for Merck, Bristol Myers Squibb, Genentech/Roche, Amgen, GlaxoSmithKline, AstraZeneca, Eli Lilly, Sanofi, and Regeneron. Julie R. Brahmer has received grant funding from AstraZeneca and Bristol Myers Squib. Rakhi P. Naik has received funding from Rigel pharmaceuticals. All disclosures are unrelated to the subject matter of this manuscript. The authors did not receive support from any organization for the submitted work.

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Supplementary Information

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277_2021_4690_MOESM1_ESM.docx

Supplementary file1 Reported cases of hematological immune-related adverse events in the literature. This table summarizes the case report and case series reported in the literature. Data on the age of the patient, sex, tumor type, treatment, diagnostic workup, time from immune checkpoint blockade initiation were extracted. Data on re-challenge on immunotherapy and recurrence of the hematologic immune-related adverse event were also collected. Data was clustered by type of immune-related adverse event (DOCX 150 KB)

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Ghanem, P., Marrone, K., Shanbhag, S. et al. Current challenges of hematologic complications due to immune checkpoint blockade: a comprehensive review. Ann Hematol 101, 1–10 (2022). https://doi.org/10.1007/s00277-021-04690-x

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  • DOI: https://doi.org/10.1007/s00277-021-04690-x

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