Glucarpidase Enhances Kidney Recovery and Reduces Complications in High-Dose Methotrexate Toxicity: Study

"In patients with methotrexate-associated acute kidney injury (MTX-AKI), glucarpidase treatment was linked to higher adjusted odds of kidney recovery and a quicker time to recovery. Additionally, glucarpidase use was associated with a lower adjusted odds of developing grade ≥2 transaminitis and grade ≥2 neutropenia," the researchers reported.

Glucarpidase, a carboxypeptidase enzyme that aids in breaking down and removing methotrexate from the body, was approved by the FDA in 2012 to treat patients with toxic methotrexate levels due to kidney failure. However, as researchers pointed out, its approval was based on limited data. While it was known that glucarpidase quickly reduces methotrexate levels in the blood, there have been no rigorous studies to assess whether it improves clinical outcomes in patients with methotrexate toxicity.

To address this gap, Shruti Gupta, Brigham and Women's Hospital, Boston, Massachusetts, United States, and colleagues aimed to examine the association between glucarpidase administration and outcomes in adults with MTX-AKI across 28 cancer centers in the U.S., utilizing a sequential target trial emulation framework.

The primary endpoint was kidney recovery at hospital discharge, defined as survival to discharge with a serum creatinine level less than 1.5 times the baseline and without the need for dialysis. Key secondary endpoints included time-to-kidney recovery, neutropenia, transaminitis on day 7, and time-to-death. Multivariable logistic and Cox regression models were used to analyze patients who received glucarpidase within 4 days of MTX initiation versus those who did not.

The following were the key findings of the study:

• Out of 708 patients with MTX-AKI, 29.5% (209) received glucarpidase.
• 25.8% of patients experienced a primary endpoint event.
• Glucarpidase treatment was associated with a 2.70-fold higher adjusted odds of kidney recovery.
• Patients receiving glucarpidase had faster kidney recovery (aHR 1.88).
• Glucarpidase treatment was linked to lower risks of grade ≥2 neutropenia (aOR 0.50) and grade ≥2 transaminitis (aOR 0.50) on day 7.
• There was no significant difference in time-to-death (aHR 0.76).

The study showed that patients with methotrexate-associated acute kidney injury (AKI) had significantly improved odds of kidney recovery when treated with glucarpidase (Voraxaze). Glucarpidase treatment increased the chances of kidney recovery by 2.7 times compared to no treatment. Additionally, it resulted in faster kidney recovery and reduced risks of severe neutropenia and transaminitis.

"The benefits were particularly noticeable among females and patients with stage 3 AKI, though the latter finding wasn't statistically significant. These results highlight glucarpidase's positive impact on kidney recovery and potentially on other organs as well," the researchers concluded.

Reference:

Gupta S, Kaunfer SA, Chen KL, Dias JA, Vijayan A, Rajasekaran A, Prosek J, Truong HL, Wood A, Bassil C, Renaghan AD, Shah CV, Zhang J, Glezerman I, Carlos C, Kelly K, Passero CJ, Drappatz J, Abudayyeh A, Shin D, Sperati CJ, Yelvington BJ, Kanduri SR, Neyra JA, Edmonston D, Shirali AC, Bansal A, Geara A, Mithani Z, Ziolkowski SL, Rashidi A, Jakubowski J, Pujari A, Bond DA, Dotson EK, Wall SA, Patton JT, Barreto JN, Hermann SM, Sheikh MS, Baz RC, Lee JH, Lucchesi N, Kolman M, Rasheed MA, Afzal A, Kang D, Mahesh A, Hsu R, Nicolaysen A, Tefera K, Schretlen C, Miller RM, Velez JCQ, Flannery AH, Aklilu AM, Anand S, Chandrasekhara S, Donley V, Patel A, Ni J, Krishnamurthy S, Ali R, Yilmam OA, Wells SL, Ortega JL, Green-Lingren OL, Leaf RK, Sise ME, Nayak L, LaCasce AS, Leung N, Leaf DE. Glucarpidase for Treatment of High-Dose Methotrexate Toxicity. Blood. 2025 Jan 6:blood.2024026211. doi: 10.1182/blood.2024026211. Epub ahead of print. PMID: 39760780.