Future Directions in Indolent Systemic Mastocytosis Treatment

With new data and treatment strategies discussed at the American Academy of Allergy, Asthma & Immunology (AAAAI) annual meeting, attention is increasingly turning to long-term management and unmet needs in indolent systemic mastocytosis.

In this exclusive MedPage Today video, Cem Akin, MD, PhD, of the University of Michigan in Ann Arbor, outlines key areas of ongoing research, including dose optimization, bone health, and anaphylaxis risk, and what they may mean for clinical practice moving forward.

Following is a transcript of his remarks:

I think the future directions will involve perhaps a better dose adjustment for some patients. Does one dose work for all patients who may have different levels of disease severity, different levels of disease burden? For example, as we are finding out with the PIONEER 50-mg dose cohort, those patients respond better to a higher dose than patients perhaps with lower mast cell burden. So that’s one of the improvements in our knowledge that I’m hoping to achieve in the next few years.

The other important factors would be the effects of these drugs on other disease comorbidities we see like osteoporosis, for example. There is preliminary data, again presented at the AAAAI meeting, that both bezuclastinib and avapritinib [Ayvakit] are affecting the bone turnover markers and actually improving the bone density. And osteoporosis is seen in one out of three patients in mastocytosis. So it is a significant comorbidity, and these patients face the risk of compression fractures, especially in the vertebral bones.

And are these patients with mastocytosis and osteoporosis treated differently than patients with osteoporosis without mastocytosis? So in other words, would a tyrosine kinase inhibitor have a role as a standalone therapy or maybe in combination with other treatments like bisphosphonates or monoclonal antibodies? So that’s another piece of information that we look forward to gaining.

And then, last but not the least, what are the effects of these kinase inhibitors in anaphylaxis? Because that’s another very significant comorbidity in mastocytosis. Up to 40% of patients with systemic mastocytosis have these severe allergic-type reactions called anaphylaxis in their lifetime. And we still don’t have good data whether these kinase inhibitors, while they are reducing the mast cell burden, are they also reducing the risk of anaphylaxis?

So those are the main short-term information that I’m looking forward to gaining in the next few years.