Asparaginase toxicity in Hispanic adult and pediatric patients with acute lymphoblastic leukemia: current understanding

ABSTRACT

Introduction

Asparaginase is essential to chemotherapy regimens for acute lymphoblastic leukemia (ALL). Survival of patients with ALL has improved since incorporating asparaginase into chemotherapy backbones. Hispanic patients have a higher incidence of ALL than other ethnicities and suffer inferior outcomes. The inferior outcome of Hispanics is due to several factors, including the increased incidence of high-risk genetic subtypes and susceptibility to treatment-related toxicity.

Areas covered

We summarize the current knowledge of asparaginase-related toxicity by comparing their incidence between Hispanic and non-Hispanic patients. These toxicities include hypersensitivity, hepatotoxicity, pancreatitis, thrombosis, and hypertriglyceridemia. The PubMed database and Google Scholar were used to search for this review from October 2022 to June 2023.

Expert opinion

Except for hepatotoxicity and hypertriglyceridemia secondary to asparaginase-based treatments, which may develop more frequently among Hispanic patients with ALL, other toxicities were comparable between Hispanic and non-Hispanic patients. Nevertheless, studies with larger cohorts and more accurate capturing of Hispanic ethnicity should be conducted to fill the gaps in the current knowledge.

KEYWORDS:

• Acute lymphoblastic leukemia (ALL)
• Asparaginase
• Drug toxicity
• Hepatotoxicity
• Hispanics
• Pharmacogenetics

Article highlights

• Asparaginase is a critical component of the chemotherapy regimen used to treat acute lymphoblastic leukemia.

• The increased intolerance of intensive therapy or discontinuation of asparaginase treatment contributes to the inferior outcome of patients with ALL.

• Hypersensitivity, hepatotoxicity, pancreatitis, thrombosis, and hypertriglyceridemia are the most common toxicities of asparaginase.

• Except for some evidence of higher incidence of hepatotoxicity and hypertriglyceridemia, Hispanics exhibited toxicities comparable to non-Hispanics.

• Large clinical prospective studies incorporating ancestral genotyping are needed to determine the toxic profile of asparaginase in Hispanic patients with ALL.

Declaration of interest

W. Stock has disclosed they are on the advisory board for Amgen, Beam, GlaxoSmithKline, Jazz Pharmaceuticals, Kite, Kronos, Kura, Pfizer, Servier, and Syndax; have received honoraria from Up to Date, Jazz Pharmaceuticals, Pfizer, and Research to Practice; have received service honoraria from the American Society of Hematology – Blood Advances. E. Orgel has received consulting fees from Jazz Pharmaceuticals and Seagen Inc. 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.

Additional information

Funding

This paper funded by the University of Southern California, the School of Pharmacy Seed Fund, The Norris Cancer Center pilot fund, STOP Cancer pilot funding, and The Ming Hsieh Institute Foundation grants, the National Institutes of Health (NIH) P30, NIH-NCI 1R01CA248381–01A1 and in part by NIH grant 5P30CA014089–45 (all to H. Alachkar).