Glucarpidase for treatment of high-dose methotrexate toxicity
Abstract
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.
Article Details
Authors (73)
Shruti Gupta
Department of Anatomy and Cell Biology, The George Washington University
Sarah A. Kaunfer
4Division of Renal Medicine, Brigham and Women’s Hospital, Boston, MA
Kevin L. Chen
4Department of Biostatistics, Harvard TH Chan School of Public Health, Boston, MA
Julie-Alexia Dias
4Division of Renal Medicine, Brigham and Women’s Hospital, Boston, MA
Anitha Vijayan
5Division of Nephrology, Washington University School of Medicine, St. Louis, MO
Arun Rajasekaran
7Division of Nephrology, Department of Medicine, University of Alabama at Birmingham, Birmingham, AL
Jason M. Prosek
8Division of Nephrology, Department of Internal Medicine, The Ohio State University, Columbus, OH
Huong L. Truong
9Department of Pharmacy, Mayo Clinic, Rochester, MN
Anthony Wood
11Medical Oncology and Hematology, Arizona Center for Cancer Care, Phoenix, AZ
Claude Bassil
13Department of Onco-Nephrology, H. Lee Moffitt Cancer Center and Research Institute, Tampa, FL
Amanda D. Renaghan
14Division of Nephrology, University of Virginia Health System, Charlottesville, VA
Chintan V. Shah
15Division of Nephrology, Hypertension, and Renal Transplant, Department of Medicine, University of Florida, Gainesville, FL
Jingjing Zhang
Ilya Glezerman
17Renal Service, Memorial Sloan Kettering Cancer Center, New York, NY
Christopher Carlos
19Division of Nephrology, Department of Medicine, University of California San Francisco, San Francisco, CA
Katherine Kelly
20Department of Medicine, Indiana University School of Medicine, Indianapolis, IN
Christopher J. Passero
21Renal-Electrolyte Division, Department of Medicine, University of Pittsburgh, Pittsburgh, PA
Jan Drappatz
22Department of Neurology and Medicine, University of Pittsburgh, Pittsburgh, PA
Ala Abudayyeh
23Division of Internal Medicine, Section of Nephrology, University of Texas MD Anderson Cancer Center, Houston, TX
Daniel Sanghoon Shin
24Division of Hematology and Oncology, David Geffen School of Medicine at University of California Los Angeles, Los Angeles, CA
C. John Sperati
25Division of Nephrology, Johns Hopkins University School of Medicine, Baltimore, MD
Bradley J. Yelvington
26Department of Oncology Pharmacy, Vanderbilt University Medical Center, Nashville, TN
Swetha R. Kanduri
27Department of Nephrology, Ochsner Health, New Orleans, LA
Javier A. Neyra
Daniel Edmonston
29Division of Nephrology, Department of Medicine, Duke University School of Medicine, Durham, NC
Anushree C. Shirali
30Section of Nephrology, Department of Internal Medicine, Yale University School of Medicine, New Haven, CT
Anip Bansal
31Division of Renal Diseases and Hypertension, University of Colorado Anschutz Medical Campus, Aurora, CO
Abdallah Geara
32Renal-Electrolyte and Hypertension Division, University of Pennsylvania, Philadelphia, PA
Zain Mithani
Susan L. Ziolkowski
34Division of Nephrology, Department of Medicine, Stanford University School of Medicine, Palo Alto, CA
Arash Rashidi
35Division of Nephrology and Hypertension, University Hospitals Cleveland Medical Center, Cleveland, OH
Jonathan Jakubowski
5Division of Nephrology, Washington University School of Medicine, St. Louis, MO
Ashwini Pujari
7Division of Nephrology, Department of Medicine, University of Alabama at Birmingham, Birmingham, AL
David A. Bond
36Division of Hematology, Department of Internal Medicine, Ohio State University Comprehensive Cancer Center, Columbus, OH
Emily Dotson
37Department of Pharmacy, The Ohio State University, Columbus, OH
Sarah Wall
2The Ohio State University Comprehensive Cancer Center - James Cancer Hospital, Columbus, United States
John Patton
36Division of Hematology, Department of Internal Medicine, Ohio State University Comprehensive Cancer Center, Columbus, OH
Jason N. Barreto
9Department of Pharmacy, Mayo Clinic, Rochester, MN
Sandra M. Herrmann
38Division of Nephrology and Hypertension, Department of Internal Medicine, Mayo Clinic, Rochester, MN
Mohammad S. Sheikh
Rachid Baz
1Department of Malignant Hematology, H. Lee Moffitt Cancer Center and Research Institute, Tampa, FL
Jamie Lee
UCLA, Los Angeles, California, United States
Nicholas Lucchesi
14Division of Nephrology, University of Virginia Health System, Charlottesville, VA
Michael Kolman
15Division of Nephrology, Hypertension, and Renal Transplant, Department of Medicine, University of Florida, Gainesville, FL
Muhammad Ahsan Rasheed
16Division of Nephrology, Department of Medicine, Thomas Jefferson University, Philadelphia, PA
Afsheen Afzal
17Renal Service, Memorial Sloan Kettering Cancer Center, New York, NY
Dasol Kang
17Renal Service, Memorial Sloan Kettering Cancer Center, New York, NY
Amrita Mahesh
19Division of Nephrology, Department of Medicine, University of California San Francisco, San Francisco, CA
Raymond K. Hsu
19Division of Nephrology, Department of Medicine, University of California San Francisco, San Francisco, CA
Anthony Nicolaysen
40Division of Nephrology, Department of Medicine, University of California, Los Angeles, CA
Kibrewessen Tefera
40Division of Nephrology, Department of Medicine, University of California, Los Angeles, CA
Claire Schretlen
25Division of Nephrology, Johns Hopkins University School of Medicine, Baltimore, MD
Ryan M. Miller
26Department of Oncology Pharmacy, Vanderbilt University Medical Center, Nashville, TN
Juan Carlos Velez
27Department of Nephrology, Ochsner Health, New Orleans, LA
Alexander H. Flannery
42Department of Pharmacy Practice and Science, University of Kentucky College of Pharmacy, Lexington, KY
Abinet M. Aklilu
29Division of Nephrology, Department of Medicine, Duke University School of Medicine, Durham, NC
Shuchi Anand
Division of Nephrology, Department of Medicine, Stanford University, Palo Alto, CA
Soniya Chandrasekhara
44Department of Pharmacy, Stanford Healthcare, Stanford, CA
Vicki Donley
35Division of Nephrology and Hypertension, University Hospitals Cleveland Medical Center, Cleveland, OH
Ashka Patel
Jian Ni
Shobana Krishnamurthy
1Division of Renal Medicine, Brigham and Women’s Hospital, Boston, MA
Rafia Ali
1Division of Renal Medicine, Brigham and Women’s Hospital, Boston, MA
Osman A. Yilmam
1Division of Renal Medicine, Brigham and Women’s Hospital, Boston, MA
Sophia L. Wells
1Division of Renal Medicine, Brigham and Women’s Hospital, Boston, MA
Jessica L. Ortega
1Division of Renal Medicine, Brigham and Women’s Hospital, Boston, MA
Olivia L. Green-Lingren
1Division of Renal Medicine, Brigham and Women’s Hospital, Boston, MA
Rebecca K. Leaf
Department of Medicine, Massachusetts General Hospital, Boston
Meghan E. Sise
Department of Medicine, Massachusetts General Hospital, Boston
Lakshmi Nayak
4Department of Medical Oncology, Center for Neuro Oncology, Dana Farber Cancer Institute, Boston, MA
Ann S. LaCasce
3Harvard Medical School, Boston, MA
Nelson Leung
1Mayo Clinic, Rochester, United States
David E. Leaf
Division of Renal Medicine, Brigham and Women’s Hospital, Boston