Systemic Mastocytosis (SM)

Ayvakit™ (avapritinib) is a therapy approved by the US Food and Drug Administration (FDA) for the treatment of advanced systemic mastocytosis (SM), a rare disease characterized by the excessive proliferation of mast cells that accumulate in different tissues and organs, including the skin, spleen, liver, and bone marrow.1-3 Symptoms of SM include flushing, itching, hives, nausea, vomiting, bone pain, anemia, enlarged liver and spleen, and neuropsychiatric changes.2,4 

Advanced SM (AdvSM) can be subclassified into 3 different subtypes: 1) SM with an associated hematologic neoplasm (SM-AHN), representing up to 70% of cases, 2) aggressive SM (ASM), and 3) mast cell leukemia (MCL). A mutation in the KIT gene, KIT D816V, is the main factor responsible for the development of SM, and this mutation is typically also present in the cells of the hematologic neoplasm that may develop with SM. Patients with AdvSM have a median overall survival of 3.5 years or less.5 

Ayvakit is a prescription medicine indicated for the treatment of adults with unresectable or metastatic gastrointestinal stromal tumor (GIST) carrying a platelet-derived growth factor receptor alpha (PDGFRA) exon 18 mutation, as well as for the treatment of adult patients with AdvSM, including ASM, SM-AHN, and MCL.6 It was developed by Blueprint Medicines Corporation, and approved by the FDA in June 2021.7

Ayvakit Mechanism of Action, Usage, and Precautions

The active ingredient of Ayvakit is avapritinib, a new tyrosine kinase inhibitor that selectively targets the KIT D816V mutation to help reduce the proliferation of mast cells.3,5,8 The recommended dose of Ayvakit in AdvSM is 200 mg orally once daily on an empty stomach. This dose can be reduced or adjusted if the patient experiences adverse reactions. The most common adverse reactions expected with Ayvakit treatment are edema, diarrhea, nausea, and fatigue.6 

The use of Ayvakit may result in intracranial hemorrhage. A platelet count must be measured before treatment initiation and regularly after 8 weeks of treatment. Ayvakit is not recommended for patients with platelet counts lower than 50 x 109/L.6 Patients may also experience cognitive side effects with the treatment, such as confusion, drowsiness, somnolence, and hallucinations.8 These effects can lead to a reduction in dose and interruption of the treatment.6 Ayvakit may also cause fetal harm. Both male and female patients must therefore be advised to use an effective contraception method during the treatment and for an additional 6 weeks after the final dose of the drug has been administered.6

Get full prescribing information about Ayvakit on MPR

Ayvakit in Clinical Trials

The safety, pharmacokinetics, and efficacy of avapritinib was first evaluated in a phase 1, international, multicenter, open-label clinical trial. The EXPLORER trial (NCT02561988) evaluated avapritinib in adult patients diagnosed with AdvSM and other relapsed or refractory myeloid malignancies.9 This study enrolled 86 patients, of which 69 presented with confirmed AdvSM. Avapritinib was administered at 30 to 400 mg once a day. The primary endpoints of this study were the maximum tolerated dose, safety, and a recommended phase 2 dose. The overall response rate (ORR) and changes in the measured mast cell burden were secondary endpoints.3 

The results of this trial showed that avapritinib induced durable responses, with an ORR of 75% and a complete remission rate of 36%, which included a full or partial hematologic recovery. The drug also induced a reduction in marrow mast cells of at least 50% in 92% of the patients. Patients experienced a reversion of organ damage, as well as an improvement in symptoms. Even though a maximum tolerated dose was not achieved, the recommended dose for phase 2 studies was determined to be 200 mg once a day. Adverse events observed during the EXPLORER trial included periorbital edema, anemia, diarrhea, thrombocytopenia, and nausea, while intracranial bleeding occurred in 13% of all patients and in only 1% of patients without severe thrombocytopenia.3

Following the EXPLORER study, a phase 2 clinical trial, PATHFINDER (NCT03580655), was initiated.10 This is an international, multicenter, open-label, single-arm trial studying the efficacy and safety of avapritinib (200 mg once daily) in patients with AdvSM. The primary endpoint of this study is the ORR, while secondary endpoints include time to response, duration of response, progression-free survival, overall survival, changes in measures of disease burden, and safety. The interim analysis of this trial has reported an ORR of 75% and complete remission with full or partial hematologic recovery in 19% of participants. Bone marrow mast cells were reduced by at least 50% in 88% of the response-evaluable patients. An increase in quality of life of the patients was also reported. Observed adverse events included neutropenia, thrombocytopenia, and anemia.5


1. Systemic mastocytosis. Genetic and Rare Diseases Information Center (GARD). Accessed April 11, 2022.

2. Delves PJ. Mastocytosis. Merck Manual: Professional Version. Updated October 2020. Accessed April 11, 2022.

3. DeAngelo DJ, Radia DH, George TI, et al. Safety and efficacy of avapritinib in advanced systemic mastocytosis: the phase 1 EXPLORER trial. Nat Med. 2021;27(12):2183-2191. doi:10.1038/s41591-021-01538-9

4. Systemic mastocytosis. Mayo Clinic. November 20, 2020. Accessed April 11, 2022.

5. Gotlib J, Reiter A, Radia DH, et al. Efficacy and safety of avapritinib in advanced systemic mastocytosis: interim analysis of the phase 2 PATHFINDER trial. Nat Med. 2021;27(12):2192-2199. doi:10.1038/s41591-021-01539-8

6. Ayvakit. Prescribing information. Blueprint Medicines Corporation; 2021. Accessed April 11, 2022.

7. FDA approves avapritinib for advanced systemic mastocytosis. US Food and Drug Administration (FDA). Accessed April 11, 2022.

8. Patient guide to Ayvakit for advanced systemic mastocytosis. Blueprint Medicines Corporation. Accessed April 11, 2022.

9. (EXPLORER) Study of BLU-285 in patients with advanced systemic mastocytosis (AdvSM) and relapsed or refractory myeloid malignancies. September 29, 2015. Updated March 28, 2022. Accessed April 11, 2022.

10. (PATHFINDER) Study to evaluate efficacy and safety of avapritinib (BLU-285), a selective KIT mutation-targeted tyrosine kinase inhibitor, in patients with advanced systemic mastocytosis. July 9, 2018. Updated March 28, 2022. Accessed April 11, 2022.

Reviewed by Harshi Dhingra, MD, on 4/12/2022.