Among patients with advanced systemic mastocytosis (SM) in the phase 2 PATHFINDER study, treatment with Blueprint Medicines’ avapritinib was effective and showed a promising benefit-risk profile, regardless of disease subtype or prior therapy.
Findings from the phase 2 PATHFINDER study were presented at the 12th Annual Meeting of the Society of Hematologic Oncology (SOHO 2024), held in Houston, TX, from Sept. 4 to 7, 2024.
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 recognized as a clonal mast cellMast cell A type of white blood cell produced in the bone marrow. They help defend against infections and play a key role in allergic reactions. In SM, mast cells become overactive and build up throughout the body. disorder that is driven by a mutation in the KIT D816V gene. The potent, selective KIT D816V inhibitor avapritinib has been approved for the treatment of adults with advanced SM in the United States and in Europe who have already undergone treatment with at least one prior therapy. The researchers sought to present data from the phase 2 PATHFINDER study with two years of follow-up.
The primary endpoint of PATHFINDER was overall response rate (ORR), based on response criteria of the modified International Working Group (mIWG)-Myeloproliferative Neoplasms Research and Treatment-European Competence Network on MastocytosisMastocytosis Rare disease caused by the buildup of mast cells. Cutaneous mastocytosis primarily affects the skin and is more common in children, while systemic mastocytosis affects internal organs and is more common in adults..
Learn more about SM causes and risk factors
As of Sept. 9, 2022, a total of 107 patients with centrally confirmed advanced SM had initiated avapritinib therapy—105 individuals with avapritinib 200 mg once daily and two individuals with avapritinib 100 mg twice daily.
Results of the study revealed that among 83 mIWG response-evaluable participants, the ORR was 73%, with 27% of these patients attaining a complete remission (CR) or a CR with partial hematologic recovery (CRh).
Among treatment-naïve participants, the ORR was 90%, with 40% attaining a CR or a CRh. Median TTR was 2.3 months. Median DOR, PFS and OR, however, were not reached.
Benefits were reported regardless of subtype of disease or prior treatment. In fact, reductions of 50% or greater in bone marrow mast cell burden, serum tryptaseTryptase A protein enzyme that is primarily produced by mast cells and stored in small pockets within the cells, known as granules. High levels of tryptase are a key indicator of SM. level and KIT D816V VAF were reported in 88%, 92% and 81% of patients, respectively. Additionally, a reduction of 35% or greater in spleen volume was observed in 70% of participants.
Overall, 70% of participants experienced a total clearance of mast cell aggregates and 58% had KIT D816V VAF of less than 1%. In 74% of patients with palpable spleens, their spleens became nonpalpable.
Treatment-related adverse events (TRAEs) included thrombocytopenia, periorbital edema, peripheral edema, and anemia. Treatment-related cognitive effects, which were reported in 24% of participants, were managed with dose modification. Intracranial bleeds were observed in 3.7% of patients, all of whom discontinued treatment and experienced resolution of their symptoms.
TRAEs were associated with dose reductions in 75% of patients, treatment interruptions in 64% and treatment discontinuations in 10%. There were no treatment-related deaths reported.
