The anti-cancer properties of asparagine depletion were first described in animal models as far back as the 1950s [[1], [2], [3]]. In the decades since, different forms of asparaginase have entered routine clinical practice, playing a key role in the dramatic improvement in outcomes for children and young adults with acute lymphoblastic leukemia (ALL) [4]. With its unique mechanism of action, asparaginase leads to impaired protein synthesis in leukemic lymphoblasts due to their dependence on exogenous sources of asparagine, ultimately inducing apoptosis. It can also deplete the cerebrospinal fluid (CSF) of asparagine, thereby exerting its effects across the blood-brain barrier [5, 6]. This effective agent for ALL, when combined with more traditional cytotoxic chemotherapy, is generally utilized therapeutically for younger patients.

Systemic depletion of asparagine is also linked to various adverse effects (AEs). Even the earliest studies in children and adults identified a range of complications, including hepatic steatosis, hypersensitivity reactions, nausea, somnolence, and pancreatitis [7]. These have been particularly challenging in adults, which have led many clinicians and investigators to limit or avoid its use in this vulnerable population. Nonetheless, panels of experts have provided guidance on how to approach these complications to maintain appropriate use of these agents [8, 9]; missing scheduled doses can lead to inferior outcomes [10], underscoring the importance of this challenging issue.

Two specific populations identified as having an increased risk of experiencing asparaginase-associated toxicity are patients who are older and/or obese. Delivering asparaginase-containing regimens to patients with ALL with these characteristics has proven to be particularly challenging. There are several recent reviews that discuss the use of asparaginase broadly, some of which address the difficulties using this drug class in older and/or obese adults [[11], [12], [13]]. The focus of this review will be the approach to delivering asparaginase to adults with obesity, highlighting the evidence where it exists and providing recommendations to practitioners and investigators where data are lacking.