Mifamurtide in metastatic and recurrent osteosarcoma: A patient access study with pharmacokinetic, pharmacodynamic, and safety assessments

P. M. Anderson, P. Meyers, E. Kleinerman, K. Venkatakrishnan, D. P. Hughes, C. Herzog, W. Huh, R. Sutphin, Y. M. Vyas, V. Shen, A. Warwick, N. Yeager, C. Oliva, B. Wang, Y. Liu, A. Chou

Research output: Contribution to journalArticlepeer-review

53 Scopus citations


Purpose: This non-randomized, patient-access protocol, assessed both safety and efficacy outcomes following liposomal muramyl-tripeptide-phosphatidylethanolamine (L-MTP-PE; mifamurtide) in patients with high-risk, recurrent and/or metastatic osteosarcoma. Methods: Patients received mifamurtide 2mg/m2 intravenously twice-weekly ×12 weeks, then weekly ×24 weeks with and without chemotherapy. Serum concentration-time profiles were collected. Adverse events within 24hours of drug administration were classified as infusion-related adverse events (IRAE); other AEs and overall survival (OS) were assessed. Results: The study began therapy in January 2008; the last patient completed therapy in October 2012. Two hundred five patients were enrolled; median age was 16.0 years and 146/205 (71%) had active disease. Mifamurtide serum concentrations declined rapidly in the first 30minutes post-infusion, then in a log-linear manner 2-6hours post-dose; t1/2 was 2hours. There were no readily apparent relationships between age and BSA-normalized clearance, half-life, or pharmacodynamic effects, supporting the dose of 2mg/m2 mifamurtide across the age range. Patients reported 3,679 IRAE after 7,482 mifamurtide infusions. These were very rarely grade 3 or 4 and most commonly included chills+fever or headache+fatigue symptom clusters. One- and 2-year OS was 71.7% and 45.9%. Patients with initial metastatic disease or progression approximated by within 9 months of diagnosis (N=40) had similar 2-year OS (39.9%) as the entire cohort (45.9%) Conclusions: Mifamurtide had a manageable safety profile; PK/PD of mifamurtide in this patient access study was consistent with prior studies. Two-year OS was 45.9%. A randomized clinical trial would be required to definitively determine impact on patient outcomes.

Original languageEnglish (US)
Pages (from-to)238-244
Number of pages7
JournalPediatric Blood and Cancer
Issue number2
StatePublished - Feb 2014
Externally publishedYes


  • Biologic therapy
  • L-MTP-PE
  • Macrophage activation
  • Mifamurtide
  • Osteosarcoma
  • Pharmacokinetics

ASJC Scopus subject areas

  • Pediatrics, Perinatology, and Child Health
  • Hematology
  • Oncology


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