Mifamurtide for the treatment of nonmetastatic osteosarcoma

Abstract

Introduction: The standard treatment for osteosarcoma requires both macroscopic surgical wide resection and postoperative multi-drug chemotherapy in neoadjuvant and adjuvant settings. However, the 5-year event-free survival has remained at a plateau of 60-70% of patients with nonmetastatic osteosarcoma for more than 30 years.

Areas covered: Mifamurtide (liposomal muramyl tripeptide phosphatidylethanolamine; L-MTP-PE) is a new agent. L-MTP-PE is a nonspecific immunomodulator, which is a synthetic analog of a component of bacterial cell walls. L-MTP-PE activates macrophages and monocytes as a potent activator of immune response in addition to standard chemotherapy. It also improves the overall survival from 70 to 78% and results in a one-third reduction in the risk of death from osteosarcoma. This review summarizes the most recent findings about L-MTP-PE and its therapeutic application for nonmetastatic osteosarcoma.

Expert opinion: Recently, L-MTP-PE has been approved in Europe for the treatment of nonmetastatic osteosarcoma with chemotherapy. L-MTP-PE in combination with traditional treatment is expected to go mainstream and to be beneficial for patients with osteosarcoma. Information about potential benefit regarding mifamurtide use in the neoadjuvant setting (i.e., before surgery) and/or usefulness of L-MTP-PE in metastatic in relapsed and metastatic osteosarcoma requires analysis of expanded access and/or future clinical trials of L-MTP-PE in high-burden and low-burden situations.

Figures

Figure 1

The molecular structure of liposomal muramyl tripeptide phosphatidyl ethanolamine (L-MTP-PE).

Figure 1

The molecular structure of liposomal muramyl tripeptide phosphatidyl ethanolamine (L-MTP-PE).

Figure 2

Nod2 is an intracellular MDP sensor. Monocytes/macrophages activation by L-MTP-PE is mediated via Nod2. L-MTP-PE is selectively phagocyted by monocytes and macrophages after intravenous administration. L-MTP-PE is released into the cytosol and degraded to MDP. Nod2 binding to MDP activates NF-κB and influences the innate immune response. Abbreviations: Nod2; nucleotide-binding oligomerization domain 2, MDP; muramyl dipeptide, L-MTP-PE; liposomal muramyl tripeptide phosphatidyl ethanolamine, NF-κB; nuclear factor-kappa B.

Figure 3

Tolerability of mifamurtide. Major side effects in 248 patients with advanced cancer including 51 patients with osteosarcoma [, , –66].