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

Abstract

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

• Authors: Carle Paul, Beatrix Sans, Felipe Suarez, Philippe Casassus, Stéphane Barete, Fanny Lanternier, Catherine Grandpeix-Guyodo, Patrice Dubreuil, Fabienne Palmérini, Colin D Mansfield, Paul Gineste, Alain Moussy, Olivier Hermine, Olivier Lortholary
• Journal: American journal of hematology (Am J Hematol) Vol. 85 Issue 12 Pg. 921-5 (Dec 2010) ISSN: 1096-8652 [Electronic] United States
• PMID: 21108325 (Publication Type: Clinical Trial, Phase II, Journal Article, Multicenter Study, Research Support, Non-U.S. Gov't)
• Copyright: © 2010 Wiley-Liss, Inc.

Chemical References

• Benzamides
• Piperidines
• Pyridines
• Thiazoles
• masitinib

Topics

• Adult
• Benzamides
• Dose-Response Relationship, Drug
• Drug-Related Side Effects and Adverse Reactions
• Female
• Humans
• Male
• Mastocytosis, Cutaneous (complications, drug therapy)
• Mastocytosis, Systemic (complications, drug therapy)
• Middle Aged
• Mutation, Missense
• Piperidines
• Pyridines
• Thiazoles (administration & dosage, adverse effects)
• Treatment Outcome