West Conshohocken, PA, Dec. 11, 2023 (GLOBE NEWSWIRE) -- BTG Pharmaceuticals, a SERB company, announces the presentation of the largest study to date of patients with high-dose methotrexate (HDMTX) associated Acute Kidney Injury (AKI) treated with and without glucarpidase. The data were shared on 9 December 2023 in an oral presentation at the American Society of Hematology meeting in San Diego, CA, by Dr. David E. Leaf, MD, MMSc, of the Division of Renal Medicine, Brigham and Women’s Hospital, and Harvard Medical School.I
Researchers from Brigham and Women's Hospital/Dana-Farber Cancer Institute and Harvard Medical School examined the clinical outcomes of 708 adults from 27 major cancer centers* across the US with HDMTX-associated AKI and compared those treated with glucarpidase to those who were not.
Among the 708 patients with HDMTX-AKI, 209 (29.5%) were treated with glucarpidase and 499 (70.5%) were not. HDMTX-AKI was defined as a ≥1.5-fold increase in serum creatinine (SCr) within 4 days following treatment with HDMTX.
Researchers found that the patients who received glucarpidase had considerably higher odds of kidney recovery by hospital discharge, a statistically significant reduction in mortality, as well as recovery from neutropenia and normalization of liver enzymes, compared to those who did not receive glucarpidase.
Their data showed:
- Treatment with glucarpidase was associated with a 2.41-fold higher adjusted odds of kidney recovery at hospital discharge (95% CI, 1.33–4.37) compared to those not treated with glucarpidase.
- The magnitude of association was considerably higher when the analysis was restricted to those treated with glucarpidase in the first 60 hours (odds ratio 4.67 [95% CI, 2.33–9.36]) and to those with AKI stage 3 (odds ratio 7.22 [95% CI, 2.70–19.31]).
- The adjusted mortality rate at 90 days among patients treated with glucarpidase was 10.1% compared to 18.2% for those not treated with glucarpidase (hazard ratio 0.45 [95% CI, 0.26–0.88]).
- Rate of kidney recovery by day 14 among patients treated with glucarpidase was 31.4% compared to 22.1% for those not treated with glucarpidase (hazard ratio 0.58 [95% CI, 0.34-0.97]).
- Treatment with glucarpidase was also associated with a lower likelihood of neutropenia and transaminitis at day 7.
“This is the largest study to date of HDMTX-AKI,” said study author Dr. Shruti Gupta, MD, MPH, Director of Onconephrology in the Division of Renal Medicine, Brigham and Women's Hospital. “It’s also the first to rigorously examine whether glucarpidase improves clinical outcomes in patients with HDMTX toxicity compared to controls not treated with glucarpidase.”
“There is currently wide variation in the use of glucarpidase across institutions,” said Dr. Leaf. “Although this is an observational study, our data strongly support use of glucarpidase in patients with HDMTX-AKI, particularly in those who can receive it early (first 60 hours following initiation of HDMTX) and those with severe (stage 3) AKI.”
The presentation abstract is freely available from the American Society of Hematology conference website here: “Clinical Outcomes in Patients with High-Dose Methotrexate Toxicity Treated with Vs. without Glucarpidase”
About High-Dose Methotrexate (HDMTX):
High-Dose Methotrexate (HDMTX) is defined as methotrexate doses >500 mg/m2 and is a cornerstone of treatment for osteosarcoma, leukemia and lymphoma involving the central nervous system. Up to 12% of all patients undergoing HDMTX therapy may experience HDMTX-induced AKI which can cause significant toxicity, including bone marrow suppression and hepatotoxicity.ii Recent publications have also shown that in studies of adult patients with lymphoma, the overall incidence of AKI was 19%. iii
About Voraxaze (glucarpidase):
Voraxaze cleaves methotrexate into inactive metabolites for a nonrenal pathway of elimination. In all 22 treatment-evaluable patients, methotrexate concentrations were reduced by ≥97% within 15 minutes of administration and was maintained at a > 95% reduction up to 8 days in 20 of the 22 patients. iv
Voraxaze is a carboxypeptidase indicated to reduce toxic plasma methotrexate concentration (greater than 1 micromole per liter) in adult and pediatric patients with delayed methotrexate clearance (plasma methotrexate concentrations greater than 2 standard deviations of the mean methotrexate excretion curve specific for the dose of methotrexate administered) due to impaired renal function.
Limitations of Use: Voraxaze® is not recommended for use in patients who exhibit the expected clearance and expected plasma methotrexate concentration. Reducing plasma methotrexate concentration in these patients may result in subtherapeutic exposure to methotrexate.
About BTG Pharmaceuticals:
BTG, a SERB company, is dedicated to helping healthcare providers treat patients with critical conditions, focusing on emergency care and rare diseases. For over 30 years we have helped treat complex and life-threatening conditions; supporting clinicians, healthcare systems and governments while offering hope to patients and their families. As a fully integrated company, we have the experience and capabilities to acquire, develop, and manufacture our medicines to the highest standards, and make them available worldwide through our secure supply chain. learn more at serb.com.
For further information contact:
Chris Sampson, Corporate Communications Director
chris.sampson@serb.com; Mobile: +44 (0)7773 251 178
* Cancer Centers included: Brigham and Women’s Hospital, Boston, MA; Duke Cancer Center, Durham, NC; Dana-Farber Cancer Institute, Boston, MA; Indiana University Melvin and Bren Simon Comprehensive Cancer Center, Indianapolis, IN; Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins University, Baltimore, MD; Massachusetts General Hospital, Boston, MA: Mayo Clinic, Rochester, MN; MD Anderson Cancer Center, Houston, TX; Memorial Sloan Kettering, New York, NY; Moffitt Cancer Center, Tampa, FL; Oschner Health System, New Orleans, LA; Ohio State University Comprehensive Cancer Care Center, Columbus, OH; Stanford Cancer Institute, Stanford, CA; Sidney Kimmel Cancer Center at Jefferson Health, Philadelphia, PA; University of Alabama Birmingham Hospital, Birmingham, AL; UCLA Jonsson Comprehensive Cancer Center, Los Angeles, CA; UCSF Helen Diller Family Comprehensive Cancer Center, San Francisco, CA; University of Colorado Cancer Center, Aurora, CO; University of Florida Cancer Center, Gainesville, FL; University Hospitals Cleveland Medical Center, Cleveland, OH; University of Kentucky, Louisville, KY; University of Miami Sylvester Comprehensive Cancer Center, Miami, FL; Hospital of the University of Pennsylvania, Philadelphia, PA; University of Pittsburgh Medical Center, Pittsburgh, PA; University of Virginia Hospital, Charlottesville, VA; Vanderbilt University Medical Center, Nashville, TN; Washington University in St. Louis, St. Louis, MO; Yale New Haven Hospital, New Haven, CT
References:
- Gupta S, LaCasce A, Leaf RK, Kaunfer S, Leaf DE. Clinical Outcomes in Patients with High-Dose Methotrexate Toxicity Treated with Vs. without Glucarpidase [abstract 268]. In: 65th Annual American Society of Hematology Annual Meeting and Exposition; December 9 – 12, 2023; San Diego, CA (https://ash.confex.com/ash/2023/webprogram/Paper189432.html, accessed November 10, 2023).
- Howard SC, McCormick J, Pui CH, Buddington RK, Harvey RD. Preventing and managing toxicities of high-dose methotrexate. Oncologist. 2016;21(12):1471-1482.
- O'Donoghue DF et al. JCO Oncol Pract. 2022;18(12):e1908-e1917.
- Voraxaze®. Prescribing information. BTG International Inc.; 2019.
Voraxaze® US indication and limitations of use
- Voraxaze® is a carboxypeptidase indicated to reduce toxic plasma methotrexate concentration (greater than 1 micromole per liter) in adult and pediatric patients with delayed methotrexate clearance (plasma methotrexate concentrations greater than 2 standard deviations of the mean methotrexate excretion curve specific for the dose of methotrexate administered) due to impaired renal function.
- Limitations of Use: Voraxaze® is not recommended for use in patients who exhibit the expected clearance and expected plasma methotrexate concentration. Reducing plasma methotrexate concentration in these patients may result in subtherapeutic exposure to methotrexate.
Important safety information
Warnings and precautions
Serious Hypersensitivity Reactions
- Serious hypersensitivity reactions, including anaphylactic reactions, may occur. Serious hypersensitivity reactions occurred in less than 1% of patients
Monitoring Methotrexate Concentration/Interference with Assay
- Methotrexate concentrations within 48 hours following Voraxaze® administration can only be reliably measured by a chromatographic method due to interference from metabolites. Measurement of methotrexate concentrations within 48 hours of Voraxaze® administration using immunoassays results in an overestimation of the methotrexate concentration
Adverse reactions
- In clinical trials, the most common related adverse events (occurring in >1% of patients) were paresthesia, flushing, nausea and/or vomiting, hypotension and headache
Drug interactions
- Voraxaze® can decrease leucovorin concentration, which may decrease the effect of leucovorin rescue unless leucovorin is dosed as recommended, and may also reduce the concentrations other folate analogs or folate analog metabolic inhibitors
Please see full Prescribing Information.
