Masitinib for the treatment of systemic and cutaneous mastocytosis with handicap: a phase 2a study.

摘要: Treatment options for patients suffering from indolent forms of mastocytosis remain inadequate with the hyperactivation mast cells responsible many disease's systemic manifestations. Masitinib is a potent and highly selective oral tyrosine kinase inhibitor. A combined inhibition c-Kit Lyn make it particularly efficient in controlling activity therefore, potential therapeutic benefit mastocytosis. was administered to 25 diagnosed as having or cutaneous related handicap (i.e., disabilities associated flushes, depression, pruritus quality-of-life) at initial dose levels 3 6 mg/kg/day over 12 weeks. In accordance AFIRMM study, response based upon change clinical symptoms patient week relative baseline, regardless disease subtype. Improvement observed all primary endpoints including reduction Hamilton rating, compared baseline by 64% (P = 0.0005), 43% 0.0049), 36% 0.0077), respectively. An overall 14/25 (56%; [95%CI 37%-75%]), sustainable improvement throughout an extension phase (>60 weeks). Common adverse events were edema (44%), nausea muscle spasms (28%), rash majority which mild moderate severity significant decline frequency after weeks treatment. One experienced serious event reversible agranulocytosis. promising treatment indicates acceptable tolerability long-term regimens.