BSH 2024 | The current therapeutic landscape for indolent and advanced systemic mastocytosis

So exciting times, again, because of the tyrosine kinase inhibitors. Those patients with indolent SM, have a normal full blood count, they don’t have any end organ damage, but up to 30% can be very symptomatic. And the mainstay of treatment is anti-mediated therapy, they’re on a combination of them. But with the new trials… so avapritinib used in PIONEER, which is avapritinib at a lower dose than with the advanced disease, led to its licensing because there was a symptom burden improvement significantly as a primary endpoint met last year. So these patients had a significant, more than 50%, improvement in their symptom burden, and it’s now licensed in the US. So, it shows us that the TK inhibitors target the c-kit, they decrease the mast cell burden in these patients, particularly in the indolent with their skin, and then they lead to improvement in symptom outcomes. So now what’s happening is there are more TKIs that are wanting to be available in this space, as 80% of patients with SM have indolent disease. So we now have the SUMMIT trial with bezuclastinib being used in this arena, and moving forward there is elenestenib, which is a blueprint molecule for the same indication coming out. And even more exciting, there is a BTK inhibitor being involved. So what we’re finding for these patients with ISM who are very symptomatic is hoping to reduce their symptom burden and improve their quality of life. And with the advanced disease, we’ve got the bezuclastinib in a trial and combination therapy with a TKI and azacitidine for those patients that have AHN. So, there’s big changes with combination therapies coming forward.