Mifamurtide (L-MTP-PE) for Metastatic and Recurrent Osteosarcoma (OS): Survival and Safety Profile from a Patient Access Study

ABSTRACT Introduction and research objectives Liposomal muramyl tripeptide phosphatidyl ethanolamine (L-MTP-PE; mifamurtide) is approved for treatment of non-metastatic osteosarcoma (OS) in Europe, Israel, and Mexico. The primary objective of MTP-OS-403 was to collect information regarding the safety and tolerability of MTP in patients with high-risk OS. The open label access study called for L-MTP-PE 2mg/m2 twice /week x 24 doses, then weekly (total doses= 48 in 9 months). OS patients could receive MTP as a single agent or with appropriate chemotherapy. Results As of April 2012, 202 patients were registered at 8 participating centers. Most had metastases at initial presentation or recurrent OS. Median age was 16 yr. Time from initial diagnosis to L-MTP-PE treatment was 29 +/- 23 months (median 24 mo). Although >88% had metastases, 27% had been resected to no evidence of disease (NED) before study entry. The most common Infusion related AE (IRAE) within 24 hours of infusion were chills (37%), fever (25%), nausea (21%), headache (19%), and fatigue (15%). The most common AE (grade 3-4) other than IRAE were chemotherapy-related and included thrombocytopenia (22%), neutropenia (19%), leukopenia (18%), febrile neutropenia (16%), lymphopenia (15%), and anaemia (15%). At MDACC, there was 1 episode of pleural effusion and one episode of pericardial effusion that were possibly L-MTP-PE related. The median number of L-MTP-PE doses given was 34 (mean 30.1 +/- 17.5); 32% of these high risk OS patients received 48 doses. As of April 2012 45% (90/202) of these high risk OS patients continue to be followed for survival. Conclusion The safety profile of L-MTP-PE in high-risk OS patients is consistent with the known toxicity of the product. The infusion related AEs were generally mild to moderate. Since survival benefit in high-grade OS from MTP may be related to disease burden (i.e. achieving NED status using local control measures such as surgery and/or radiotherapy), L-MTP-PE may be more effective when used in the adjuvant setting. A randomized multi-institutional clinical trial in OS patients presenting with metastases at diagnosis should be considered. Disclosure C. Oliva: Cristina Oliva is a Takeda employee. Y. Liu: I am a Millennium employee. All other authors have declared no conflicts of interest.