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Masitinib for the treatment of systemic and cutaneous mastocytosis with handicap: a phase 2a study
Carle Paul1, Beatrix Sans, Felipe Suarez
1Université Paul Sabatier, Toulouse, France.
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.
Insights
Masitinib effectively treats indolent mastocytosis by inhibiting mast cell hyperactivation. This tyrosine kinase inhibitor improved patient handicap symptoms like flushes and pruritus, showing promise for long-term therapy.
Area of Science:
- Pharmacology
- Hematology
- Oncology
Background:
- Indolent mastocytosis presents inadequate treatment options due to mast cell hyperactivation.
- Masitinib, a tyrosine kinase inhibitor, targets c-Kit and Lyn kinases, crucial in mast cell activity.
Purpose of the Study:
- To evaluate the efficacy and tolerability of masitinib in patients with indolent mastocytosis and associated handicap.
Main Methods:
- A 12-week study administered masitinib (3 or 6 mg/kg/day) to 25 patients with systemic or cutaneous mastocytosis.
- Response was assessed by clinical symptom changes related to patient handicap, including flushes, depression, pruritus, and quality-of-life.
Main Results:
- Significant improvements were observed in primary endpoints: reduced flushes (64%), Hamilton rating (43%), and pruritus (36%) at 12 weeks.
- Overall clinical response was achieved in 56% of patients, with sustained benefits during an extended treatment phase (>60 weeks).
- Common adverse events included edema and nausea; most were mild/moderate and decreased over time. One case of reversible agranulocytosis was reported.
Conclusions:
- Masitinib demonstrates therapeutic potential for indolent mastocytosis with handicap, offering significant symptom relief.
- The drug exhibits acceptable tolerability for long-term treatment regimens in this patient population.
