Study Finds Glucarpidase Improves MTX-Induced Acute Kidney Injury

According to recent study results published in Blood, glucarpidase (Voraxaze; SERB Pharmaceuticals) is a potential solution to kidney toxicity in patients who are receiving the chemotherapy drug methotrexate (MTX). Using findings from 28 cancer centers, the investigators observed an association between treatment with glucarpidase and outcomes of patients with acute kidney injury (AKI) resulting from MTX.^1,2

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The investigators explained that MTX is one of the most common chemotherapeutic agents used worldwide for cancers that affect the central nervous system; however, high doses of the agent, such as doses greater than or equal to 500 g/m², can cause severe complications, such as AKI, liver toxicity, and neutropenia.^1,2

Glucarpidase is a therapeutic agent that can rapidly clear MTX from the blood. Within 15 minutes of administration, it can convert MTX in the blood into inactive metabolites. The authors noted that despite its effects, there has not been previous research to determine if these effects can be clinically beneficial.²

“Glucarpidase is unique because it’s one of the very few potential antidotes available to counteract the high rates of toxicity caused by chemotherapy,” Shruti Gupta, MD, an associate physician in the Division of Renal Medicine at Brigham and Women’s Hospital (BWH) and founding member of the Mass General Brigham health care system, said in a news release. “Even though glucarpidase was approved by the FDA in 2012, our study is the first to provide a comprehensive assessment of its potential clinical benefits.”²

For this study, data between 2000 and 2022 from 28 US cancer studies were examined using a sequential target trial emulation framework to examine the association between glucarpidase administration and outcomes in adults with MTX-induced AKI. The investigators compared the outcomes in patients who received glucarpidase within 4 days following MTX initiation with those who did not receive MTX.^1,2

The primary end point of the study was kidney recover at hospital discharge, which was defined as survival to discharge with serum creatinine below the 1.5-fold baseline and without dependence on dialysis. Additionally, key secondary end points were time to kidney recovery, neutropenia, and transaminitis on day 7, as well as time to death.¹

Among the 708 patients with MTX-induced AKI, approximately 29.5% (n = 209) received glucarpidase. A total of 183 patients (25.8%) of the enrolled population achieved a primary end point. Overall, receiving glucarpidase was associated with a 2.70-fold higher adjusted odds of kidney recovery (95% CI, 1.69-4.31) compared with those who were not administered glucarpidase.¹

Additionally, patients who received glucarpidase had a faster time to kidney recovery (adjusted hazard ratio [aHR], 1.88, 95% CI, 1.18-3.33) and lower risks of grades 2 and higher neutropenia (adjusted odds ratio [aOR], 0.50, 95% CI, 0.28-0.91) and transaminitis (aOR, 0.50, 95% CI, 0.28-0.91) on day 7. Further, there was no observed difference between the groups in time to death (aHR, 0.76; 95 CI, 0.49-1.18).¹

“Target trial emulation is a way to effectively analyze real-world data and to draw causal inferences from it, especially when clinical trials are unavailable and would be impractical to perform,” David Leaf, MD, director of clinical and translational research in AKI at BWH’s Division of Renal Medicine, said in the news release. “We worked with dozens of our collaborators across 28 sites to extract granular data from medical records—all by manual chart review—which allowed us to account for key variables in our models. This allowed us to have a high degree of confidence in our findings.”²

According to the authors, the data suggests that glucarpidase may improve both renal and extrarenal outcomes in patients with MTX-induced AKI. They encourage health care professionals to consider using this therapy to help treat patients who are on chemotherapy and have AKI.^1,2

“FDA approval is only the first step. If people aren’t using the drug, then patients aren’t benefiting from it,” Leaf said. “Our findings offer [health care professionals] evidence-based data supporting glucarpidase.”²

REFERENCES

1. Gupta S, Kaunfer SA, Chen KL, et al. Glucarpidase for Treatment of High-Dose Methotrexate Toxicity. Blood 2025; blood.2024026211. doi:10.1182/blood.2024026211

2. Mass General Brigham. Study Finds Chemotherapy Antidote Could Improve Recovery after Chemotherapy-Induced Kidney Toxicity. News release. January 6, 2025. Accessed January 10, 2025. https://www.massgeneralbrigham.org/en/about/newsroom/press-releases/drug-could-improve-recovery-after-chemotherapy-induced-kidney-toxicity