Diagnosing and Treating Patients With Indolent and Advanced Systemic Mastocytosis

At the 2023 Great Debates & Updates in Hematologic Malignancies meeting in Boston, Massachusetts, Daniel DeAngelo, MD, PhD, Dana-Farber Cancer Institute, Boston, Massachusetts, shares insights into recent treatment developments and diagnostic criteria for patients with indolent and systemic mastocytosis. 

In his presentation, Dr Deangelo focuses on the differentiation between patients with indolent disease versus smoldering and advanced disease. He also discusses study findings on the use of tyrosine kinase inhibitors (KIT) for the treatment of patients with mastocytosis. 

Transcript: 

Hi, my name is Dan DeAngelo. I'm Chief of the Division of Leukemia at the Dana-Farber Cancer Institute in Boston. I'm here at the Great Debates and Updates [in Hematologic Malignancies] in Boston at the meeting. 

My presentation today will be on systemic mastocytosis, a relatively rare disease, but one that is complicated. I've tried to focus my talk on the diagnostic dilemmas, trying to separate how to make a diagnosis of systemic mastocytosis, and most importantly, how to differentiate between those patients with indolent disease versus smoldering and advanced disease. It is the patients with advanced systemic mastocytosis that have a shortened life expectancy, but patients with smoldering and indolent disease still have a lot of systemic symptoms.

I'm also presenting and reviewing data from midostaurin as well as avapritinib, the 2 FDA-approved agents for patients with advanced disease, and reviewing some of the data on the indolent systemic mastocytosis trial, as well as trying to update on new developments in both indolent and advanced systemic mastocytosis, some of the new therapeutic options that are available to patients.

In terms of the treatment for advanced systemic mastocytosis, there are 2 good drugs now that have been both FDA approved. Midostaurin, which was approved a while ago, is a pan-tyrosine kinase [inhibitor], also approved in FLT3-positive acute leukemias. It does have an issue with some gastrointestinal toxicity, and although patients have nice responses, they seldom get into complete remissions. 

Avapritinib, a more specific and sensitive and potent KIT inhibitor has been shown in patients with advanced disease to elicit complete remissions, and these complete remissions sometimes can be very durable. For patients with advanced systemic mastocytosis of all 3 subtypes, we've seen really robust responses in terms of the overall response rate, but as I alluded to, improvement in the complete remission rate and therefore improvement in the overall survival. This is a huge development for patients with advanced disease.

In addition, patients with indolent systemic mastocytosis, as I've alluded to, are patients who have a normal life expectancy but are on polypharmacy to try and improve their symptoms. The addition of low-dose avapritinib was recently approved in June of this year for the treatment of patients with indolent disease in terms of improving their symptoms, and thereby reducing some of the polypharmacy that's required for symptom control. 

I'll also present data on the bezuclastinib, which is a new-in-class KIT inhibitor that is currently being tested in patients with both advanced as well as non-advanced systemic mastocytosis.

Source: 

DeAngelo, D. Orphan Hematologic Malignancies-Systemic Mastocytosis and Myeloid-Lymphoid Neoplasms: Classification, Diagnosis, Genetics and Targeted Therapeutic Options. Presented at the Great Debates and Updates in Hematologic Malignancies Meeting; August 17-19, 2023; Boston, Massachusetts.