Avapritinib could be effective for treating systemic mastocytosis (SM), even in patients who have previously undergone other therapeutic strategies, according to a study recently published in Blood Advances.

“Treatment with avapritinib was associated with rapid, deep, and durable responses, including the major reduction of disease burden in SM as well as [associated hematologic neoplasm] disease components,” the authors wrote.

Overall, most patients (71%) responded well to treatment with avapritinib, and 19% even showcased complete remission with an improvement in peripheral blood count values. These results became observable after a median of 2.3 months of treatment, and those who achieved complete remission took a median time of 7.4 months for this goal.

These results were present in patients with any SM subtype, different mutations (including those associated with the worst prognosis), and varying histories of prior treatment.

Among these positive findings, reducing mast cell infiltration in the bone marrow by at least 50% was one of the most prominent effects, occurring in 89% of the participants. Likewise, the same percentage experienced decreasing levels of serum tryptase, while 66% had a KIT D816V variant allele fraction reduction. Moreover, splenic size decreased by at least 35% in 70% of cases. 

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Avapritinib was generally well tolerated; nonetheless, almost all (94%) of the patients experienced treatment-related adverse events at some point, most of which were grade 1 or 2, and 57% of participants experienced grade 3 adverse events. The most common symptoms were edema, including peripheral and periorbital, thrombocytopenia, and diarrhea.

Although 57% of the patients had to interrupt dosages, usually due to neutropenia or thrombocytopenia, cognitive disorders, or diminished white blood cell and platelet counts, 81% of all individuals continued with the drug for at least 6 months.

While this report translates into good news for patients with SM, during the 17.7-month follow-up, the median overall survival was not reached, with estimates of 80% and 65% at the 12- and 24-month marks, respectively. To obtain these results, the researchers included 31 patients with SM who had undergone prior medical treatment as part of the EXPLORER and PATHFINDER clinical trials.

All participants received a starting dose of 200 mg every 6 hours of avapritinib, an inhibitor of D816V-mutant KIT with great potency and selectivity, and they underwent successive clinical and laboratory check-ups, as described by Reiter et al.


Reiter A, Schwaab J, DeAngelo DJ, et al. Efficacy and safety of avapritinib in previously treated patients with advanced systemic mastocytosis. Blood Adv. Published online May 31, 2022. doi:10.1182/bloodadvances.2022007539