A comparative safety review of targeted therapies for acute myeloid leukemia

ABSTRACT

Introduction

Acute myeloid leukemia (AML) treatment has primarily focused on 7 + 3 chemotherapy, but in the last decade there has been a significant increase in new therapies, mostly targeted agents, approved for the treatment of AML. We performed a comparative analysis of the unique safety profile of each of these new agents.

Areas covered

We conducted a review of the current literature on public databases (PubMed, ClinicalTrials.gov, and U.S. Food and Drug Administration) regarding new AML drugs that were approved from 2017 to 2023.

Expert opinion

The diagnosis of AML typically carries a poor prognosis but with an increase in the number of drugs that are now available, patients’ outcomes are improving. With novel mechanisms of action, the use of these agents introduces different safety profiles, occasionally with adverse events not previously seen with standard chemotherapy or at different frequencies. An understanding of the drugs available and the safety concerns associated with each one is crucial to selecting the best available option for each patient, and early recognition and appropriate management of drug-related adverse effects.

KEYWORDS:

• Acute myeloid leukemia
• CPX-351
• FLT3 inhibitor
• Gemtuzumab ozogamicin
• Glasdegib
• IDH inhibitor
• Venetoclax

Article highlights

• The link between Midostaurin and ILD or pneumonitis remains unclear, but it should be stopped immediately if either is suspected.

• Studies indicate that gilteritinib causes rapid proliferation of leukemic blasts, so patients should be monitored closely for DS.

• IDH inhibitors also cause rapid proliferation of mutated AML cells which leads to elevated risk for IDH-DS, noninfectious leukocytosis, and TLS.

• Enasidenib inhibits UGT1A1, which is believed to be the reason behind the rise in bilirubin without comparable rise in liver transaminases, similar to the effect seen with Gilbert syndrome.

• Venetoclax when used in combination with another agent demonstrated high risk for the occurrence of an infection-related adverse reaction.

• A significant number of patients receiving CPX-351 were noted to have bleeding and infection related adverse reactions which are believed to be due to strong bone marrow suppression.

• Hepatotoxicity, including VOD, remains a concern with GO, but the risk is significantly lower with its recently approved reduced fractionated dosing schedule.

Declaration of interests

J Cortes is a consultant for Pfizer, Novartis, Rigel, and BMS. J Cortes has also received research support (for his institution) from Pfizer and Novartis. 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 disclosures

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

Supplementary material

Supplemental data for this article can be accessed online at https://doi.org/10.1080/14740338.2023.2289176

Additional information

Funding

This paper was not funded.