- D1.530 - Patient Experience of Most Burdensome Nonadvanced Systemic Mastocytosis Symptoms From the Pivotal Summit Trial of Bezuclastinib

Systemic mastocytosis (SM) is characterized by mast cell (MC) infiltration and activation, driven primarily by the KIT p.D816V mutation. Nonadvanced systemic mastocytosis (NonAdvSM), the most prevalent group of SM subtypes, is associated with a range of debilitating symptoms which can significantly impair quality of life (QoL).

Bezuclastinib (bezu) is an oral, potent, and selective type 1 tyrosine kinase inhibitor targeting KIT D816V. In the Summit trial assessing bezu in patients (pts) with NonAdvSM, clinically meaningful symptom improvement and significant reductions in objective disease markers were demonstrated along with a favorable safety profile. 

Here, we report findings from a subset of Summit pts who participated in entry and exit interviews.  

Summit pts had ongoing moderate-to-severe symptomatology despite best supportive care medications. They were randomized to receive either bezu 100 mg or placebo (pbo) daily for 12 weeks (Part 1) or 24 weeks (Part 2). 

Interviews were conducted with consenting pts prior to start of treatment (entry) and again after 12 or 24 weeks on treatment (exit). Entry interviews explored symptom burden, diagnostic journey, and disease experience; exit interviews solicited perceptions of treatment experience. 

Pts in Summit with entry interviews (n=71) identified their most bothersome symptom, with the most frequently reported symptoms being tiredness (39%), brain fog (30%), itching (25%), or difficulty concentrating (24%).  

Of pts with exit interviews (n=74), 48 received 24 weeks of treatment in Part 2. The most bothersome symptoms were reported as improved or resolved in a majority of pts receiving 24 weeks of bezu: 65% (tiredness), 80% (brain fog), 87% (itching), and 81% (difficulty concentrating) improved or resolved. In contrast, pts receiving pbo most often reported no change or worsening of symptoms. For pts receiving pbo, the most bothersome symptoms were reported as improved or resolved in 33% (tiredness), 13% (brain fog), 22% (itching), and 25% (difficulty concentrating). Pts considered improvements to be meaningful because they experienced fewer symptoms and less impact on their daily lives. 

Summit exit interviews contextualized treatment benefits with bezu, with pts reporting meaningful improvements in all most bothersome symptoms. Overall, these findings highlight the QoL and symptom improvements pts with NonAdvSM experienced while treated with bezu.