Clinical challenges and promising therapies for chemotherapy-induced thrombocytopenia

ABSTRACT

Introduction: Chemotherapy-induced thrombocytop enia (CIT) is a common complication of cancer treatment causing chemotherapy delays, dose reductions, and treatment discontinuation, negatively impacting treatment outcomes and putting patients at risk for bleeding complications. There is no FDA-approved agent available to manage CIT.

Areas covered: This article covers the diagnosis, definitions, and clinical challenges of CIT, and then focuses on the therapeutics developed to manage CIT. The first-generation thrombopoietic agents (oprelvekin and recombinant human thrombopoietins) are reviewed for critical background and context, followed by a detailed discussion of the data for the thrombopoietin receptor agonists (TPO-RAs) to manage CIT. Efficacy of TPO-RAs in treatment and prevention of CIT, as well as safety concerns such as the risk of thromboembolic complications, are reviewed in detail. For this review, a PubMed/MEDLINE literature search was undertaken for relevant articles published from 1995–2021.

Expert opinion: After over two decades of drug development for CIT, multiple clinical trials and observational studies have found TPO-RAs, in particular romiplostim, to be safe and effective agents to manage patients with CIT, although no agent is yet FDA-approved for this indication. Active management of CIT with TPO-RAs is likely to improve oncologic outcomes, although additional data are needed. Phase 3 trials are ongoing.

KEYWORDS:

• Chemotherapy
• chemotherapy-induced thrombocytopenia
• thrombocytopenia
• supportive care
• romiplostim
• eltrombopag
• thrombopoietin
• thrombopoietin receptor agonist
• bleeding

Article highlights

• Although chemotherapy-induced thrombocytopenia (CIT) is a common complication of cancer treatment, there is no FDA-approved agent available to manage CIT.

• Two primary subtypes of CIT are recognized clinically: nadir CIT and persistent CIT.

• The first-generation thrombopoietic agents oprelvekin, rhTPO, and PEG-rHuMGDF were efficacious to treat CIT but adverse events limited their development and use.

• The second generation of thrombopoietic agents, the thrombopoietin receptor agonists (TPO-RAs), are a promising new treatment modality to manage CIT. Encouraging observational studies and early-phase trials have been completed.

• Phase 3 trials of TPO-RAs to manage CIT are ongoing and have potential to change the standard-of-care, as active management of CIT with TPO-RAs may improve oncologic outcomes.

Acknowledgments

H. Al-Samkari is the recipient of the Harvard KL2/Catalyst Medical Research Investigator Training Award and the American Society of Hematology Scholar Award.

Declaration of interest

H Al-Samkari serves as a consultant for Agios, Dova, Rigel, Argenx, Sobi, Novartis; and research funding from Agios, Dova and Amgen. GA Soff serves as a consultant for Amgen, Janssen Scientific Affairs, Bayer Pharmaceuticals, Dova/Sobi Pharmaceuticals, Bristol-Myers Squibb, Pfizer, Novartis, Antho(s) Therapeutics, Hengrui (USA) Ltd; and research funding from Amgen, Janssen Scientific Affair and Dova/Sobi Pharmaceuticals.

The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

Reviewer disclosure

Peer reviewers on this manuscript have no relevant financial or other relationships to disclose.

Additional information

Funding

This paper was not funded.