Ep. 138: KIT D816V in Anaphylaxis — What the PROSPECTOR Trial Reveals

Part of the series: The Itch Review

LISTEN TO EPISODE 138: Apple Podcast • Spotify • Amazon Music

This podcast was made in partnership with Allergy & Asthma Network.

We thank Blueprint Medicines for sponsoring this episode. While they support the show, all opinions are our own, and sponsorship doesn’t influence our content or editorial decisions. Any mention of brands is for informational purposes and not an endorsement.

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Clonal mast cell disease is often missed because symptoms vary from person to person, tryptase levels can be normal, and bone marrow biopsies are hard to get. For some people, unexplained or very severe anaphylaxis may be an early sign of a clonal mast cell disease.

In this episode, we review “Prevalence of KIT D816V in anaphylaxis or systemic mast cell activation,” published in October 2025 in the Journal of Allergy and Clinical Immunology. This paper, known as the PROSPECTOR trial, is looking at how often the KIT D816V mutation can be found using a blood test in adults who have had anaphylaxis or systemic mast cell activation symptoms.

We break down why KIT D816V matters, how it connects to systemic mastocytosis, why HaT needs to be considered, and how newer blood tests may help doctors catch clonal mast cell disease earlier.

What we cover in our episode about KIT D816V and anaphylaxis:

• Setting the stage: Understanding mast cell activation and anaphylaxis.

• Why KIT D816V matters: How this mutation fits into clonal mast cell disease, what blood testing can reveal, and when doctors still turn to a bone marrow biopsy.

• Making sense of tryptase and hereditary alpha-tryptasemia (HaT): Why baseline tryptase, the “20% + 2” rule, and HaT can make screening more complicated than it seems.

• What the PROSPECTOR trial uncovered: How often KIT D816V appeared in people with anaphylaxis, and other results on tryptase and HaT.

• How this helps patients: What these findings mean for anyone with unexplained or severe anaphylaxis, and how doctors combine KIT testing, tryptase, HaT, and symptoms to decide on next steps.

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More episodes on Mast Cell Disease

More resources about mast cell disorders

• Mast Cell Disease Toolkit

• What is Mastocytosis? Types, Symptoms, and Treatment

• Mast Cell Disease Glossary of Terms

Other podcast episodes about mast cell disease 

• Ep. 127: Management of indolent mastocytosis - A clinical yardstick

• Ep. 126: Management of mast cell activation syndrome - A clinical yardstick

• Ep. 121: Avapritinib vs Placebo in Indolent Systemic Mastocytosis - PIONEER Trial

• Ep. 118: The ISM Disconnect - Do Patients and Providers Agree on Symptom Control?

• Ep. 70 How do stress and low histamine diets impact mast cell disease?

• Ep. 63: Mast Cell Diseases & Systemic Mastocytosis: The Basic Science

• Ep. 65: The Symptoms and Triggers of Mast Cell Disease

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The Itch Review, hosted by Dr. Gupta, Kortney, and Dr. Blaiss, explores allergy and immunology studies, breaking down complex research in conversations accessible to clinicians, patients, and caregivers. Each episode provides key insights from journal articles and includes a one-page infographic in the show notes for easy reference.

Timestamps

Our episode discusses blood testing for the KIT D816V mutation

01:42 What mast cell activation syndrome means

07:20 What anaphylaxis is

10:19 Understanding KIT D816V

13:27 Tests used to look for mast cell disorders

19:14 How the PROSPECTOR trial was designed

28:41 What the PROSPECTOR trial found

39:13 Strengths and limits of the study

41:37 Doctor takeaways