Dr DeAngelo on the Effect of Avapritinib on Bone Density in Advanced Systemic Mastocytosis

“For the first time, we’re really seeing some dramatic improvements with one of the major complaints that patients [with systemic mastocytosis] have, which is the osteoporosis, osteopenia, and compression fractures.”

Daniel DeAngelo, MD, PhD, professor, medicine, Harvard Medical School; chief, Division of Leukemia, institute physician, Dana-Farber Cancer Institute, discusses the effect of avapritinib (Ayvakit) on bone density in patients with advanced systemic mastocytosis.

At the 2024 ASH Annual Meeting, investigators presented bone density data from a subset of patients with systemic mastocytosis who received avapritinib in the phase 2 PATHFINDER study (NCT03580655).

Avapritinib has emerged as the standard of care for patients with advanced systemic mastocytosis based on findings from the phase 1 EXPLORER study (NCT02561988) and the PATHFINDER trial, which both demonstrated high response rates, including durable complete remissions, with the agent in this population, DeAngelo begins. Despite its efficacy, avapritinib is associated with certain toxicities, including cognitive impairment and intracranial bleeding, particularly in patients with thrombocytopenia, he details. These toxicities have led the FDA to approve its use only in patients with platelet counts greater than 50 x 10⁹/L, DeAngelo notes.

Newly presented data from the PATHFINDER study assessed the effect of avapritinib on bone morbidity, DeAngelo continues. Among patients who underwent serial bone DXA scans, improvements in osteopenia, osteoporosis, and myelosclerosis were observed; this was reflected by sustained improvements in lumbar T-scores over more than 3 years of follow-up. These findings highlight avapritinib’s potential to address a significant unmet need in patients with systemic mastocytosis, particularly those with indolent systemic mastocytosis, where osteopenia and osteoporosis are highly prevalent and challenging to manage, DeAngelo says.

The broader applicability of these findings, including whether lower doses of avapritinib in indolent systemic mastocytosis or the use of other agents in this population can yield similar benefits, remains to be determined, he notes. However, these results represent a meaningful advance in addressing bone-related complications in systemic mastocytosis, such as osteopenia, osteoporosis, and compression fractures, which are common and significantly affect patient quality of life, DeAngelo concludes.