Study will assess HMA and KIT inhibitors to treat SM subtype

The study will look at combined therapies for an SM subtype.

A new study will begin soon to determine the safety of combining hypomethylating agents and the KIT-inhibitor avapritinib in patients with systemic mastocytosis (SM) with an associated hematologic neoplasm (AHN); the abstract is set to be presented soon to the American Hematology Association Annual Meeting and Exposition.

“To date, the combination of HMA and KIT inhibitors has not been clinically evaluated,” the authors said. ”In this study, we aim to assess the safety and tolerability of the combination of avapritinib and decitabine in patients with SM-AHN.”

There are five subtypes of SM: indolent SM, the most common and least severe subtype; smoldering SM, which can progress to more serious illness; aggressive SM; SM with an associated hematologic neoplasm; and mast cell leukemia, the rarest and most severe subtype.

SM-AHN is an SM subtype in which aggressive SM coexists with another hematological malignancy not associated with mast cells. The AHN component can include a variety of hematological cancers, including chronic myelomonocytic leukemia (CML), acute myeloid leukemia (AML) and myelodysplastic syndrome. 

Read more about SM causes and risk factors

SM-AHN is usually more severe than SM alone, as patients experience symptoms and complications of both conditions.

The effectiveness of avapritinib for patients with different subtypes of advanced SM is well documented, but some patients with SM-AHN experienced progression of the hematological neoplasm component despite improving their SM component.

In light of this evidence, some experts considered that administering simultaneous therapy for the AHN component while administering avapritinib is necessary in patients with SM-AHN.

Hypomethylating agents are the therapy of choice for the hematological neoplasms most commonly associated with SM. Therefore, the authors aim to assess the safety and tolerability of this combination. 

“Hypomethylating agents (HMA) form the backbone of therapy for advanced myelodysplastic syndrome (MDS) and myelodysplastic/myeloproliferative neoplasm (MDS/MPN); hematologic neoplasms most likely to co-occur with SM in patients … with SM-AHN,” the authors said.

The study will recruit 34 patients with SM and advanced AHN shown by a high Revised International Prognostic Scoring System (IPSS-R) score to determine the optimal dose of both drugs.

The study’s primary endpoint is determining the optimal dose of the combined treatment. Secondary endpoints include the overall response rate and the incidence of adverse effects.