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.”
What are the types of SM?
There are five subtypes of SM: indolent SMIndolent SM A subtype of nonadvanced SM caused by the abnormal accumulation of mast cells in the bone marrow and other organs. Indolent SM accounts for around 90% of SM cases., the most common and least severe subtype; smoldering SMSmoldering SM A subtype of nonadvanced SM, with a higher mast cell burden than the indolent subtype. Smoldering SM has a higher likelihood of progressing to an advanced form., which can progress to more serious illness; aggressive SMAggressive SM A subtype of advanced SM marked by a high mast cell burden that leads to organ damage. Aggressive SM accounts for less than 10% of SM cases.; SM with an associated hematologic neoplasm; and mast cell leukemiaMast cell leukemia The most severe subtype of SM, caused by the rapid buildup of immature mast cells in the bone marrow and blood. Mast cell leukemia accounts for less than 5% of SM cases and has a poor prognosis., 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 SMAdvanced SM In these subtypes of SM, mast cells begin to damage organs. Advanced SM includes the subtypes aggressive SM, mast cell leukemia and SM with an associated hematological neoplasm. 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 neoplasmMyeloproliferative neoplasm SM used to be classified as a type of myeloproliferative neoplasm, a group of rare blood cancers characterized by an overaccumulation of blood cells in the bone marrow. (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.
