Thanai Pongdee, MD

Clinicians who weigh symptom control and biomarker response more heavily than quality of life risk overlooking the emotional and social toll of 

). Even when symptoms and biomarkers appear controlled, patients may still experience daily fear, activity avoidance, and social withdrawal.

In this Q&A, Thanai Pongdee, MD, of Mayo Clinic, discussed 

4-year data from the PIONEER trial showing that avapritinib continues to improve emotional well-being

 and social functioning in patients with ISM, extending beyond symptom and biomarker control alone.

The analysis, presented at the European Academy of Allergy & Clinical Immunology (EAACI) 2026 Annual Meeting in Istanbul, followed 226 patients treated with avapritinib 25 mg once daily, with a median treatment duration of 46.5 months.

Mean total symptom score on the ISM-Symptom Assessment Form and mean percentage change in the Mastocytosis Quality of Life Questionnaire total score both showed continued improvement from baseline through 1 and 4 years. Nearly half of patients reported less fear of an allergic reaction after long-term treatment, and by 3 years, 52% of patients had reduced or discontinued use of ≥ 1 class of best supportive care medication. The safety profile remained consistent through 4 years, with treatment-related discontinuations occurring in just 3% of patients and no new safety signals identified.

Avapritinib's 4-Year PIONEER Data Show Durable QoL Benefits in ISM

What does it mean to see clinically meaningful improvements in emotional well-being and social functioning, not just symptom or biomarker control, in this PIONEER analysis?

 It's very meaningful because not only do we want to see symptom improvement, but importantly we want patients to be able to function in their daily activities, whether it be work or social situations, because disease, being chronic in nature, can significantly impact those kinds of activities and emotional well-being, and create social isolation and negative feelings. Anything that can improve those aspects of a disease is as equally important as symptom control.

How do these emotional well-being findings, including reduced fear, loneliness, and sadness, compare with what you've observed in this patient population before treatment?

 The trial findings and report have certainly mirrored what we observe and hear from patients in the clinic, which is good to see. Many patients report being able to go out to eat with friends or family and not have to worry like they used to. They used to avoid going out to social functions because they were very worried about something happening or some symptom flare occurring.

After being on treatment, they've seen those symptoms improve or go away in many respects. They're able to engage in many activities that they otherwise would have avoided. In a similar way, on the work front, various work activities that may have been avoided or not even attempted may have limited their progress in the workplace. Having those restrictions or fears lessened or removed has certainly helped in that aspect as well.

How should this data change the way clinicians evaluate treatments and assess ISM beyond mast cell burden or serum tryptase?

 We always have to keep the patient at the center. It's nice to see biomarkers of disease improve, and that's obviously very important…but at the end of the day, the patients have to feel better, be able to function in an unrestricted manner. That's really the whole point of taking medicine, especially from a patient point of view.

Nearly half of patients reported less fear of an allergic reaction. How significant is anaphylaxis-related anxiety as a driver of quality of life in ISM, and how does avapritinib appear to address it?

 The fear of anaphylaxis or other allergic reactions significantly impacts the majority of patients with SM. There's this constant worry that this could happen at any time, and many of the medicines we have hopefully can reduce that risk of occurrence. It makes rational sense to think that if you're decreasing mast cell burden, the likelihood of such events would decrease.

Now, that wasn't a primary endpoint in the study. There was some retrospective evidence that avapritinib may help reduce risk of anaphylactic events. We published a short report to that effect, but that's still an open question, and it's being more thoroughly investigated in a current trial.

All I have to say is decreasing that risk and consequently the fear of that happening really frees patients to do activities that we would consider pretty typical that would have otherwise been avoided. Someone who never went out to eat, never went to a school reunion, never went to an employee picnic, things a lot of us take for granted, can [now] enjoy [these] activities.

Key Takeaway from This 4-Year Pioneer Analysis

What's the key takeaway for clinicians who currently weigh symptom control or biomarker response more heavily than quality of life measures?

 It's something you can't forget. All those aspects of treatment are very important, but we can't lose sight of quality of life.

How might these findings shape conversations with patients about what to expect when starting avapritinib?

 Patients want to know how they're going to feel. They want to understand what the drug is doing, and its mechanism of action.

At the end of the day, they want to know how it's going to make them feel better: “Is there a certain way it's going to help me feel better? Is it going to help my skin symptoms or my gastrointestinal symptoms, or should everything be better? Am I going to keep taking all the medicines I take now?”

Most patients have polypharmacy, and these things are all connected. If the disease burden is less, then I would expect symptoms to get better. Hopefully that means I don't have to [prescribe] as many medicines, and then all that equals greater quality of life.

What remains unknown about the durability of these emotional and social functioning benefits, and what follow-up data are you hoping to see?

 What was very encouraging in the data is that, at least at the 4-year cutoff, all aspects of improvement, whether it be symptoms, disease burden, or quality of life, are all durable improvements. Certainly, longer-term data is more encouraging and more reassuring, so keeping track of those features over time would be good to see.

Safety looked very good over the long term, with low incidence of any safety issues over 4 years. Patients always ask, "Well, how about in 5 years, 10 years, 15 years, if I keep taking this drug?" Seeing that long-term data will be very reassuring for everyone involved.

Watch parts 1 and 2 of the interview with Pongdee here: 

Avapritinib 4-Year PIONEER Data: Sustained QoL Gains in ISM

Avapritinib 4-Year Data Show Durable Quality of Life Gains in ISM

Pongdee T. Avapritinib 4-Year PIONEER Data: Sustained QoL Gains in ISM. HCPLive. Published July 13, 2026. Accessed July 27, 2026. 

https://www.hcplive.com/view/avapritinib-4-year-pioneer-data-ism-quality-of-life

Pongdee T. Avapritinib 4-Year Data Show Durable Quality of Life Gains in ISM. HCPLive. Published July 16, 2026. Accessed July 27, 2026. 

https://www.hcplive.com/view/avapritinib-4-year-pioneer-data-ism-pongdee

Broesby-Olsen S, Siebenhaar F, Oude Elberink H, et al. Mastocytosis Treated With Avapritinib: Updated 4-Year Results From The PIONEER Trial. Presented at European Academy of Allergy & Clinical Immunology (EAACI) 2026 Annual Meeting from June 12-15, 2026 in Istanbul, Türkiye.

Articles

Four-year follow-up of avapritinib in indolent systemic mastocytosis demonstrates sustained, clinically meaningful improvements in emotional well-being and social functioning alongside symptom and biomarker gains. Among 226 patients receiving avapritinib 25 mg once daily (median exposure 46.5 months), ISM-SAF total symptom scores and mastocytosis-specific QoL measures continued to improve through years 1 and 4. Nearly half reported reduced fear of allergic reactions, and by year 3, 52% decreased or stopped at least one supportive medication class. Safety remained consistent, with 3% treatment-related discontinuations.

Thanai Pongdee, MD, discusses how PIONEER data reveal quality of life gains that go beyond symptom and biomarker control in indolent systemic mastocytosis.

. Even when symptoms and biomarkers look controlled, patients may experience daily fear, activity avoidance, and social withdrawal.

, Thanai Pongdee, MD, of Mayo Clinic, discussed the equal importance of these 3 domains—symptom control, biomarker response, and quality of life—when it comes to avapritinib.

“We have to keep in mind quality of life because that's really what's affecting patients…the most on a day-to-day basis," Pongdee said.

The 4-year PIONEER analysis, presented at the European Academy of Allergy & Clinical Immunology (EAACI) 2026 Annual Meeting in Istanbul by Pongdee and colleagues, showed that avapritinib continues to improve emotional well-being and social functioning in patients from baseline through 1 and 4 years, as reflected in ISM-Symptom Assessment Form and Macrocytosis Quality of Life Questionnaire scores.

“Longer-term data is more encouraging and more reassuring,” Pongdee said. “Certainly, keeping track of those features over time would be good to see.”

Pongdee said the safety profile remained consistent through 4 years, with low rates of treatment-related discontinuation and no new safety signals identified.² Continued follow-up on symptom control, quality of life, and safety will help clinicians counsel patients with ISM who are considering long-term avapritinib therapy, he said.

Counseling Patients Starting Avapritinib for ISM

According to Pongdee, patients starting avapritinib typically have 2 main questions: how the drug works, and how it will make them feel. He added that many are also managing polypharmacy for ISM, so as symptoms improve, patients often hope to reduce their other medications.

The data reflected that pattern, as 52% of participants had reduced or discontinued ≥ 1 class of best supportive care therapy by 3 years.¹,² Pongdee observed the most reductions with cromolyn sodium, anti-immunoglobulin E therapy, and H1 and H2 antihistamines.

“If the disease burden is less, then I would expect my symptoms to get better, and then hopefully that means I don't have to take as many medicines, and then all that equals greater quality of life,” Pongdee said.

, along with the first part of our interview with Pongdee.

Reported disclosures for Pongdee include GlaxoSmithKline and Blueprint Medicines Corporation.

Pongdee T. Avapritinib 4-Year PIONEER Data: Sustained QoL Gains in ISM. HCPLive. Published on July 13, 2026. 

Videos

Thanai Pongdee, MD, discusses 4-year PIONEER data showing avapritinib's quality of life, symptom, and safety benefits in indolent systemic mastocytosis remain durable.

Four-year data from the PIONEER trial show that avapritinib continues to improve emotional well-being and social functioning in patients with 

, extending beyond symptom and biomarker control alone, according to Thanai Pongdee, MD, of Mayo Clinic.

The analysis, presented at the European Academy of Allergy & Clinical Immunology (EAACI) 2026 Annual Meeting in Istanbul, followed 226 patients who initiated avapritinib 25 mg once daily across parts 1, 2, and 3 of the trial. The median treatment duration was 46.5 months, ranging from 0.7 to 67.2 months.

Emotional and Social Functioning Gains With Avapritinib 

Pongdee said the findings matter because chronic disease burden extends well beyond physical symptoms. Patients with ISM often withdraw from daily activities out of fear that a flare could occur without warning.

“We want patients to be able to function in their daily activities, whether it be work or social situations, because [the] disease, being chronic in nature, can significantly impact those kinds of activities and emotional well-being. Anything that can improve those aspects of a disease [is] as equally important as symptom control.”

Nearly half of patients reported less fear of an allergic reaction after long-term treatment, according to Pongdee. He said anaphylaxis-related anxiety is a major driver of quality-of-life impairment in ISM because reactions are frequently unpredictable.

"There's this constant worry that this could happen at any time," Pongdee said. He pointed to a previously published retrospective report suggesting avapritinib may reduce anaphylactic event risk, though he noted this remains under further investigation and was not a primary endpoint of PIONEER.

Sustained Quality of Life Improvement in ISM

Mean total symptom score on the ISM-Symptom Assessment Form (ISM-SAF TSS) and mean percentage change in Mastocytosis Quality of Life Questionnaire (MC-QoL) total score both showed continued improvement from baseline through 1 (-17.66 and -30.96, respectively) and 4 years (-17.66 and -35.41). These extended findings build on the placebo-controlled portion of PIONEER, in which avapritinib produced rapid, durable, and clinically meaningful improvements in ISM symptoms and quality of life compared with placebo through 24 weeks.

By 1 year, 31% of patients (n = 69) had reduced or discontinued use of ≥ 1 class of best supportive care (BSC) medication; by 3 years, that proportion rose to 52% (n = 118). The largest reductions were seen with cromolyn sodium (36.5%), anti-immunoglobulin E therapy (34.5%), and H1 (31.2%) and H2 (28.8%) antihistamines.

The safety profile of avapritinib with a median treatment duration of approximately 4 years remained consistent with what was previously reported in the placebo-controlled portion of the trial. Discontinuations due to treatment-related adverse events remained limited, occurring in 3% of patients (n = 6); grade ≥ 3 treatment-related adverse events stayed low.

The most frequently reported treatment-related adverse events were edema events, most of which were grade 1. Rates of cognitive adverse events and increased transaminases remained low and similar to placebo from the earlier controlled portion of the study, and no intracranial bleeds were observed. 1 death occurred during the study but was deemed unrelated to treatment, attributed to anaphylaxis in the context of atrial fibrillation in a patient with a prior history of both conditions.

“Decreasing [the anaphylaxis] risk…frees people…to do activities that we would consider pretty typical [but] would have otherwise been avoided,” Pongdee concluded. “Someone who never went out to eat, never went to a school reunion, [never attended] an employee picnic—things that a lot of us take for granted—can also enjoy those same activities.”

Akin C. Long-Term PIONEER Data Reinforce Avapritinib’s Benefit–Risk Profile in ISM, with Cem Akin, MD. HCPLive. March 3, 2026. Accessed July 13, 2026. 

https://www.hcplive.com/view/long-term-pioneer-data-reinforce-avapritinib-benefit-risk-profile-ism-akin-md

4-year PIONEER data show avapritinib sustains symptom control and improves emotional well-being and social functioning in ISM, per Thanai Pongdee, MD. 

Pongdee also discussed the changing treatment landscape for indolent systemic mastocytosis and questions that will need to be answered in the field. 

Looking Deeper Into ISM and KIT Mutations, with Thanai Pongdee, MD

Indolent systemic mastocytosis (ISM) is a rare, clonal mast cell disease caused by 

 D816V mutations. Patients typically experience chronic debilitating symptoms including allergic type symptoms, gastrointestinal symptoms, and fatigue, and it often takes years for a correct diagnosis to be made.

Thanai Pongdee, MD, allergist-immunologist at Mayo Clinic, is actively engaged in ISM research and coauthored a number of abstracts that were presented at the 

2025 American Academy of Allergy, Asthma, and Immunology (AAAAI)/World Allergy Organization (WAO) Joint Congress

, February 28-March 3, in San Diego, California.

One abstract Pongdee presented focused on using more sensitive duplex sequencing (DS) to detect 

mutations that were undetectable by droplet digital PCR (ddPCR) in patients that received avapritinib in the PIONEER (NCT03731260), and associations with response.

 Pongdee and colleagues found that 70% of participants with undetectable 

 D816V by ddPCR had KIT mutations, including non-D816V mutations, detected by DS.

spoke with Pongdee to learn more about the findings from the analysis. He also discussed the changing treatment landscape of ISM and questions that remain to be answered past the introduction of novel therapies.

“Once drugs are approved, then what? What's the course of disease after that? We really don't know that, so that'll be interesting to watch over time, and [effects on] some of the longer-term issues with mastocytosis, [including higher risk of] osteoporosis or bone disease,” Pongdee said. “Can these drugs affect or alter the course?”

Pongdee’s disclosures include GSK, Blueprint Medicines, and Sanofi.

Systemic mastocytosis. Mayo Clinic. Updated November 20, 2020. Accessed March 11, 2025. 

https://www.mayoclinic.org/diseases-conditions/systemic-mastocytosis/symptoms-causes/syc-20352859

Pongdee T, Vachhani P, Tashi T, et al. Responses to Avapritinib in Patients Without Detectable KIT Mutations by ddPCR in Peripheral Blood Highlight Diagnostic Challenges and Opportunities in Indolent Systemic Mastocytosis. Presented at: 2025 AAAAI/WAO Joint Congress, February 28-March 3. Abstract 965