Is anyone on Imatinib for Systemic Mastocytosis and has the KITD816V mutation?

[MastoMan]

Link below says that it is to be used "for disease without the KIT[D816V] mutation".

nice.org.uk/guidance/gid-ta...

orpha.net/consor/cgi-bin/OC...

[Jess-UKMasto Administrator]

Hi there. The research literature is in agreement with NICE that imatinib is generally not used in people with the D816V mutation. Imatinib, unfortunately, does not kill off mast cells with the D816V mutation, so is not useful for that purpose.

One article that is available for free that I think is a great resource is the annual update from Animesh Pardanani, a haematologist at Mayo Clinic in the US, who specialises in mastocytosis. Here's what he says about imatinib: "Imatinib has a limited therapeutic role in SM; effective cytoreduction is limited to those with imatinib‐sensitive KIT mutations." Also, "Imatinib mesylate (IM): demonstrates in vitro efficacy against wild‐type KIT and certain trans‐membrane (F522C) and juxta‐membrane (V560G) KIT mutants, but not the common kinase (D816V) domain mutants. Similarly, not all juxta‐membrane mutations may be sensitive to IM (eg, V559I)."

Here's a link to the paper: onlinelibrary.wiley.com/doi...

If a haematologist is proposing imatinib for a patient with the D816V mutation it would be wise to consider a second opinion, in my view. While there may be the very occasional circumstances where this is appropriate because there is something else going on, this choice would be best made by a haematologist who is very experienced with mastocytosis.