KIT D816V in Focus: Optimizing Diagnosis and TKI Therapy in Advanced Systemic Mastocytosis

Advanced SM is about 10% of all SM.

When it is just SM and there's no other hematologic neoplasm and you have organ damage, we see findings that's aggressive SM.

When you have SM with another associated hematologic neoplasm, that's SMAHN.

And then we have mast cell leukemia, which is the third form.

So advanced SM comes in these three flavors, most common being the SMAHN.

And there one has to be careful whether the organ damage is from the SN component or the AHN component.

The C findings in systemic mastocytosis define this organ damage from the infiltrating mast cells.

That's a very important concept.

C finding is where the mast cells are causing the organ damage.

Organ damage is where the focus is.

This can be subtle.

It can be obvious.

Now, of course, there are symptoms.

They are less prominent in advanced disease, but you can have GI, skin, CNS, constitutional and musculoskeletal.

And then one can also have not just in advanced SM, but SM as a whole, bone loss.

So low bone density, osteopenia, osteoporosis.

Just as a concept, the symptoms, the anaphylaxis in advanced SM, they are less common than The KIT VH16V mutation underlies the vast majority of cases of SM.

90 to 95% is no different in advanced SM, where the VAFs tend to be higher than in those with indolent disease.

And we know that higher KIT VAFs actually have a prognostic importance in the context of certain therapies.

we found that if you have less than a 25% reduction of the KIT-VAF, that correlates with a worse outcome.

There are, of course, other mutations which are adverse as well and are often seen.

Just one comment on the KID-D816V testing, especially in indolent SM, where the VAFs are lower.

It may be missed if one just uses an NGS panel, which is what we often start with.

So it's important if SM is suspected and you're not picking it up on the NGS, then you get a highly sensitive assay for KID-D816V, such as a digital droplet PCR or an allele-specific oligonucleotide PCR.