Shruti Gupta, Sarah Allison Kaunfer, Kevin L Chen, Julie-Alexia Dias, Anitha Vijayan, Arun Rajasekaran, Jason Prosek, Huong L Truong, Anthony Wood, Claude Bassil, Amanda DeMauro Renaghan, Chintan V Shah, Jingjing Zhang, Ilya Glezerman, Christopher Carlos, Katherine Kelly, Christopher J Passero, Jan Drappatz, Ala Abudayyeh, Daniel Shin, C John Sperati, Bradley J Yelvington, Swetha Rani Kanduri, Javier A Neyra, Daniel Edmonston, Anushree C Shirali, Anip Bansal, Abdallah Geara, Zain Mithani, Susan L Ziolkowski, Arash Rashidi, Jonathan Jakubowski, Ashwini Pujari, David A Bond, Emily K Dotson, Sarah A Wall, John T Patton, Jason N Barreto, Sandra M Herrmann, Mohammad Salman Sheikh, Rachid C Baz, Jae Hui Lee, Nicholas Lucchesi, Michael Kolman, Muhammad Ahsan Rasheed, Afsheen Afzal, Dasol Kang, Amrita Mahesh, Raymond Hsu, Anthony Nicolaysen, Kibrewessen Tefera, Claire Schretlen, Ryan M Miller, Juan Carlos Q Velez, Alexander H Flannery, Abinet M Aklilu, Shuchi Anand, Soniya Chandrasekhara, Vicki Donley, Ashka Patel, Jian Ni, Shobana Krishnamurthy, Rafia Ali, Osman A Yilmam, Sophia L Wells, Jessica L Ortega, Olivia L Green-Lingren, Rebecca Karp Leaf, Meghan E Sise, Lakshmi Nayak, Ann S LaCasce, Nelson Leung, David E Leaf
{"title":"Glucarpidase for Treatment of High-Dose Methotrexate Toxicity.","authors":"Shruti Gupta, Sarah Allison Kaunfer, Kevin L Chen, Julie-Alexia Dias, Anitha Vijayan, Arun Rajasekaran, Jason Prosek, Huong L Truong, Anthony Wood, Claude Bassil, Amanda DeMauro Renaghan, Chintan V Shah, Jingjing Zhang, Ilya Glezerman, Christopher Carlos, Katherine Kelly, Christopher J Passero, Jan Drappatz, Ala Abudayyeh, Daniel Shin, C John Sperati, Bradley J Yelvington, Swetha Rani Kanduri, Javier A Neyra, Daniel Edmonston, Anushree C Shirali, Anip Bansal, Abdallah Geara, Zain Mithani, Susan L Ziolkowski, Arash Rashidi, Jonathan Jakubowski, Ashwini Pujari, David A Bond, Emily K Dotson, Sarah A Wall, John T Patton, Jason N Barreto, Sandra M Herrmann, Mohammad Salman Sheikh, Rachid C Baz, Jae Hui Lee, Nicholas Lucchesi, Michael Kolman, Muhammad Ahsan Rasheed, Afsheen Afzal, Dasol Kang, Amrita Mahesh, Raymond Hsu, Anthony Nicolaysen, Kibrewessen Tefera, Claire Schretlen, Ryan M Miller, Juan Carlos Q Velez, Alexander H Flannery, Abinet M Aklilu, Shuchi Anand, Soniya Chandrasekhara, Vicki Donley, Ashka Patel, Jian Ni, Shobana Krishnamurthy, Rafia Ali, Osman A Yilmam, Sophia L Wells, Jessica L Ortega, Olivia L Green-Lingren, Rebecca Karp Leaf, Meghan E Sise, Lakshmi Nayak, Ann S LaCasce, Nelson Leung, David E Leaf","doi":"10.1182/blood.2024026211","DOIUrl":null,"url":null,"abstract":"<p><p>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 U.S 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% CI, 1.69-4.31) compared to 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.</p>","PeriodicalId":9102,"journal":{"name":"Blood","volume":" ","pages":""},"PeriodicalIF":21.0000,"publicationDate":"2025-01-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Blood","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1182/blood.2024026211","RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"HEMATOLOGY","Score":null,"Total":0}
Glucarpidase for Treatment of High-Dose Methotrexate Toxicity.
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 U.S 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% CI, 1.69-4.31) compared to 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.
期刊介绍:
Blood, the official journal of the American Society of Hematology, published online and in print, provides an international forum for the publication of original articles describing basic laboratory, translational, and clinical investigations in hematology. Primary research articles will be published under the following scientific categories: Clinical Trials and Observations; Gene Therapy; Hematopoiesis and Stem Cells; Immunobiology and Immunotherapy scope; Myeloid Neoplasia; Lymphoid Neoplasia; Phagocytes, Granulocytes and Myelopoiesis; Platelets and Thrombopoiesis; Red Cells, Iron and Erythropoiesis; Thrombosis and Hemostasis; Transfusion Medicine; Transplantation; and Vascular Biology. Papers can be listed under more than one category as appropriate.