A new analysis from Italy and Spain looked at almost 400 people (ages 4–40) with non-metastatic high-grade osteosarcoma of the arms or legs. It suggests that adding mifamurtide after surgery may help higher-risk patients—especially those whose tumours didn’t respond well to chemotherapy before surgery—when combined with high-dose ifosfamide. It is encouraging, but not definitive for everyone.

What is mifamurtide?

Mifamurtide (also called L-MTP-PE) is a type of immunotherapy. Rather than attacking cancer cells directly, it activates immune cells (monocytes and macrophages) to better recognise and fight cancer.

• Availability: Licensed in Europe/UK for patients aged 2–30 with non-metastatic osteosarcoma after complete surgery.
• Not available in the United States currently

Plain English: Mifamurtide is an immune “nudge” given regularly for many months after surgery, alongside standard chemotherapy.

How is osteosarcoma usually treated?

Most people receive chemotherapy before and after surgery. A common combination is MAP:

• Methotrexate
• Adriamycin (doxorubicin)
• Platinum (cisplatin)

After surgery, doctors examine the removed tumour. If ≥90% of the tumour cells are dead, it’s called a good response. Less than that is a poor response. This response strongly predicts the chance of the cancer returning.

What did the new study do?

• Everyone started with two cycles of MAP before surgery.
• Tumours were tested for P-glycoprotein (Pgp)—a protein that can pump chemotherapy drugs out of cancer cells.
• After surgery:
• Pgp-positive + good response: MAP + mifamurtide
• Pgp-positive + poor response: High-dose ifosfamide (plus a short course of doxorubicin) + mifamurtide
• Pgp-negative (any response): MAP only

Mifamurtide was given twice weekly for 12 weeks, then weekly for 6 months (total 48 weeks).

What were the results?

• Follow-up: median of 70 months (~6 years).
• Across all patients:
• 5-year event-free survival (no relapse, new cancer, or death): ~65%
• 5-year overall survival: ~75%

Where the benefit was most clear

Patients who had a poor response to pre-surgery chemotherapy and were Pgp-positive did better when they received mifamurtide plus high-dose ifosfamide after surgery than similar patients who did not.

Important caution: When researchers adjusted for other differences between groups, the overall advantage for mifamurtide became less certain. This is because the study wasn’t a randomised trial.

What does this mean for patients and families?

• Most promising group: People at higher risk—those whose tumours were Pgp-positive and didn’t respond well to pre-surgery chemotherapy—may benefit from mifamurtide + high-dose ifosfamide after surgery.
• Not a blanket yes: The study doesn’t prove mifamurtide helps all patients. It also can’t show whether Pgp-negative patients would benefit, because they didn’t receive mifamurtide in this analysis.
• Access varies: Mifamurtide is available in Europe/UK (age limits apply) but not in the US.

In summary, this study gives hope that adding mifamurtide after surgery may reduce the risk of relapse in some higher-risk patients. But it isn’t a cure, it’s not proven for everyone, and access is uneven. For now, it’s an option to raise with your doctor, especially if you’re in Europe and in a higher-risk category.

References & Study Authors

This blog is based on: Palmerini E, Meazza C, Tamburini A, Márquez-Vega C, Bisogno G, Fagioli F, Ferraresi V, Martín Broto J, et al.
Is There a Role for Mifamurtide in Nonmetastatic High-Grade Osteosarcoma? Results From the Italian Sarcoma Group (ISG/OS-2) and Spanish Sarcoma Group (GEIS-33) Trials.
Journal of Clinical Oncology. Published 2025.
DOI: 10.1200/JCO-25-00210