Glucarpidase for treatment of high-dose methotrexate toxicity Journal Article
| Authors: | Gupta, S.; Kaunfer, S. A.; Chen, K. L.; Dias, J. A.; Vijayan, A.; Rajasekaran, A.; Prosek, J. M.; Truong, H. L.; Wood, A.; Bassil, C.; Renaghan, A. D.; Shah, C. V.; Zhang, J.; Glezerman, I.; Carlos, C.; Kelly, K.; Passero, C. J.; Drappatz, J.; Abudayyeh, A.; Shin, D. S.; Sperati, C. J.; Yelvington, B. J.; Kanduri, S. R.; Neyra, J. A.; Edmonston, D.; Shirali, A. C.; Bansal, A.; Geara, A.; Mithani, Z.; Ziolkowski, S. L.; Rashidi, A.; Jakubowski, J.; Pujari, A.; Bond, D. A.; Dotson, E.; Wall, S.; Patton, J.; Barreto, J. N.; Herrmann, S. M.; Sheikh, M. S.; Baz, R.; Lee, J.; Lucchesi, N.; Kolman, M.; Rasheed, M. A.; Afzal, A.; Kang, D.; Mahesh, A.; Hsu, R. K.; Nicolaysen, A.; Tefera, K.; Schretlen, C.; Miller, R. M.; Velez, J. C.; Flannery, A. H.; Aklilu, A. M.; Anand, S.; Chandrasekhara, S.; Donley, V.; Patel, A.; Ni, J.; Krishnamurthy, S.; Ali, R.; Yilmam, O. A.; Wells, S. L.; Ortega, J. L.; Green-Lingren, O. L.; Leaf, R. K.; Sise, M. E.; Nayak, L.; LaCasce, A. S.; Leung, N.; Leaf, D. E. |
| Article Title: | Glucarpidase for treatment of high-dose methotrexate toxicity |
| Abstract: | High-dose methotrexate (MTX) results in high rates of acute kidney injury (AKI), neutropenia, and hepatotoxicity. Glucarpidase is a recombinant enzyme that cleaves MTX, but clinical data supporting its use are scarce. We examined the association between glucarpidase administration and outcomes in adults with MTX-AKI from 28 cancer centers across the United States using a sequential target trial emulation framework. The primary end point was kidney recovery at hospital discharge, defined as survival to discharge with serum creatinine <1.5-fold baseline and without dialysis dependence. Key secondary end points were time to kidney recovery, neutropenia, and transaminitis on day 7, and time to death. Using multivariable logistic and Cox regression models, we compared outcomes in patients who received glucarpidase within 4 days following MTX initiation with those in patients who did not. Among 708 patients with MTX-AKI, 209 (29.5%) received glucarpidase. Overall, 183 (25.8%) had a primary end point event. Glucarpidase receipt was associated with a 2.70-fold higher adjusted odds of kidney recovery (95% confidence interval [CI], 1.69–4.31) compared with no glucarpidase receipt. Patients treated with glucarpidase also had faster time to kidney recovery (adjusted hazard ratio [aHR], 1.88; 95% CI, 1.18–3.33) and lower risks of grade ≥2 neutropenia (adjusted odds ratio [aOR], 0.50; 95% CI, 0.28–0.91) and grade ≥2 transaminitis (aOR, 0.50; 95% CI, 0.28–0.91) on day 7. There was no difference in time to death (aHR, 0.76; 95% CI, 0.49–1.18). These data suggest glucarpidase may improve both renal and extrarenal outcomes in patients with MTX-AKI. © 2025 American Society of Hematology |
| Keywords: | adult; controlled study; aged; major clinical study; mortality; neutropenia; paresthesia; cisplatin; diarrhea; gemcitabine; methotrexate; rituximab; drug megadose; sensitivity analysis; carboplatin; liver toxicity; nausea; odds ratio; creatinine blood level; recombinant enzyme; vasculotropin inhibitor; ifosfamide; protein tyrosine kinase inhibitor; acute kidney failure; cause of death; cancer center; folinic acid; comorbidity; hospital discharge; cotrimoxazole; pemetrexed; urine volume; aminoglycoside; hypertransaminasemia; carboxypeptidase g2; immune checkpoint inhibitor; human; male; female; article; absolute neutrophil count; urine ph |
| Journal Title: | Blood |
| Volume: | 145 |
| Issue: | 17 |
| ISSN: | 0006-4971 |
| Publisher: | American Society of Hematology |
| Date Published: | 2025-04-24 |
| Start Page: | 1858 |
| End Page: | 1869 |
| Language: | English |
| DOI: | 10.1182/blood.2024026211 |
| PUBMED: | 39760780 |
| PROVIDER: | scopus |
| DOI/URL: | |
| Notes: | Article -- Source: Scopus |
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