What is your approach to systemic treatment of a rapidly progressing, symptomatic, unresectable MPNST arising from a plexiform neurofibroma in a patient with NF1?

MPNST is a different ballgame than plexiform neurofibroma. Unfortunately, it is not chemotherapy-sensitive. We currently do not have a good option for MPNST. Perhaps clinical trial enrollment works best. We also do NGS to look for targets, apart from NF1. MEK inhibitors have been tried in the past with poor response.

If one has to try a MEK inhibitor, then Gomekli (mirdametinib) is approved for both adults and kids- it is easier to obtain from insurance. However, the approval is for plexiform neurofibroma only. I think it is reasonable to try the AIM-75 regimen in patients, but the patient should be counselled that the chances of success are very low.

The activity of the MEK inhibitor is selective for the benign NF/PN. For the malignant transformation, with aggressive behavior, the SOC chemotherapy regimens are preferred. The SARC trial tested Dox/Ifex and Ifex/VP-16, and these remain the preferred front-line regimens.