HopeFOL, or FOL of problems? Leucovorin for autistic symptoms

In late 2025, the US Food and Drug Administration (FDA) made an unprecedented announcement about approving leucovorin for autism symptoms. But the data for its use in autism is flawed. It has only been shown to be safe and effective in a rare genetic syndrome caused by a mutation in the folate receptor alpha gene (FOLR1-CFTD), for which FDA approval was granted in March 2026. Yet patients with autism are already seeking leucovorin. Why is this important in oncology? This approval could impact patients with cancer, where leucovorin is regularly used to mitigate high-dose methotrexate toxicity and enhance fluorouracil efficacy. Leucovorin shortages have been common since 2008. An increased demand for leucovorin for autistic symptoms could limit the available supply for patients with life-threatening cancers. Previous leucovorin drug shortages have led to poorer outcomes by use of less effective regimens, increased real and near-miss errors, decreased clinical trial enrollment, and increased costs. The oncology healthcare team can play a crucial role in minimizing the impact of the off-label use of leucovorin on the care of patients with cancer. As healthcare providers, we need to ensure that access to medications is available only for indications that are based on sound science and peer-reviewed research or are available within a clinical trial.