Glucarpidase (Voraxaze®), currently an investigational agent available under an open-label treatment protocol, offers great potential for the treatment of patients with or at high risk for toxicity after high-dose methotrexate (MTX) chemotherapy. The case study reported by Al-Turkmani et al. illustrates the challenges to the laboratory monitoring of MTX, especially in the glucarpidase-treated patient. Metabolite interference has long been recognized in MTX immunoassays. Although a relatively small positive bias is due to interference by 7-hydroxymethotrexate, the predominant metabolite of MTX, this case demonstrates the appreciable and unpredictable nature of metabolite interference. The high positive bias reported for this case caused by the typically minor MTX metabolite 2,4-diamino-N10-methylpteroic acid (DAMPA) rendered monitoring of MTX useless for the management of the patient. Even with the astute recognition of an analytical interference by the authors' laboratory, the patient was still subject to an additional glucarpidase dose that might have been unnecessary. Failure to recognize the interference could have lead to even further, potentially harmful interventions. I doubt other laboratories would have fared better in detecting this interference. The availability of a more specific liquid chromatography method for MTX is unlikely in most clinical laboratories. Proficiency-testing data from the College of American Pathologists for 2010 reveal that 92% of laboratories perform the fluorescence polarization immunoassay used in this case, and all of the 407 participating laboratories currently use an immunoassay platform for MTX. As Al-Turkmani et al. state, it is imperative that laboratory directors communicate with their oncology colleagues and educate them about the limitations of MTX assays, especially for the glucarpidase-treated patient. The limitations of MTX concentration monitoring should also be considered for inclusion in the package insert for glucarpidase to help disseminate this important information.
Author Contributions: All authors confirmed they have contributed to the intellectual content of this paper and have met the following 3 requirements: (a) significant contributions to the conception and design, acquisition of data, or analysis and interpretation of data; (b) drafting or revising the article for intellectual content; and (c) final approval of the published article.
Authors' Disclosures or Potential Conflicts of Interest: No authors declared any potential conflicts of interest.
Role of Sponsor: The funding organizations played no role in the design of study, choice of enrolled patients, review and interpretation of data, or preparation or approval of manuscript.
- Received for publication September 13, 2010.
- Accepted for publication September 20, 2010.
- © 2010 The American Association for Clinical Chemistry