Masitinib Improves Symptom Burden, Responses in Patients with Severe Systemic Mastocytosis

Masitinib, a selective oral tyrosine kinase inhibitor (TKI) targeting wild-type KIT, LYN, and FYN, reduced the severity of a diverse range of symptoms in patients with severely symptomatic indolent or smoldering systemic mastocytosis (ISM or SSM) who were unresponsive to other treatments, according to results from a randomized phase III trial presented by Olivier Hermine, MD, PhD, from the University of Paris Descartes, at the European Hematology Association’s 21st Congress.

Mastocytosis is designated as an orphan disease by the U.S. Food and Drug Administration and is characterized by an abnormal proliferation or activation of mast cells either in the skin or in bone marrow or other organs. Masitinib is the first drug to be evaluated in phase III in the indolent form of mastocytosis – regardless of severity, Dr. Hermine noted.

“There is currently no registered or established standard treatment for this rare condition with a high unmet medical need,” he said in a press release. “Masitinib may be an important new treatment option for these patients … with both efficacy and safety data indicating a possibility for effective long-term management of this difficult-to-treat condition.”

All 135 patients enrolled in the trial had severely symptomatic ISM or SSM (defined as at least one of the following baseline symptoms: pruritus score ≥9, ≥8 flushes per week, Hamilton rating scale for depression score ≥19, or Fatigue Impact Scale [FIS] score ≥75).

Patients received masitinib 6 mg/kg daily over 24 weeks (with a possible extension period) and were followed from eight weeks to 96 weeks post-treatment initiation.

Masitinib resulted in a significant improvement over placebo in rates of cumulative response (the study’s primary endpoint; defined as a ≥75% improvement in at least one severe baseline symptom): 18.7 percent versus 7.4 percent, respectively (odds ratio [OR] = 3.6 (95% CI 1.2-10.8; p=0.008).

Response was confirmed in sensitivity and secondary analyses, Dr. Hermine reported. For example, at week 24, masitinib-treated patients had lower tryptase levels relative to baseline, compared with patients who received placebo: 18.0 percent decrease in the masitinib arm versus a 2.2 percent increase in the placebo arm (p<0.001).

Masitinib also led to significantly better clearance of urticaria pigmentosa in patients who received the study drug compared with placebo (p=0.02).

Treatment with masitinib appeared safe and consistent with the drug’s known adverse events (AEs); toxicities were predominantly gastrointestinal or skin events and typically manageable with dose reductions. Long-term safety assessment revealed comparable rates of AEs between both treatment arms, with no deaths or life-threatening AEs in the masitinib arm.

Severe AEs with a greater than four percent difference between treatment arms were: diarrhea (9.8%), rash (5.7%), and asthenia (4.1%). The most frequent serious AEs in the masitinib arm were diarrhea (4.3%) and urticaria (2.9%).

“Data from the study’s extension period showed that masitinib was capable of maintaining remission of symptoms for over two years,” Dr. Hermine noted. “This is an important observation given that ISM and SSM are life-long conditions requiring chronic management.”


Hermine O, Chandesris MO, Livideanu CB, et al. Masitinib for the treatment of severely symptomatic indolent and smoldering systemic mastocytosis: a randomized, placebo-controlled, international, phase 3 study. Abstract S828. Presented at the EHA 21st Congress, June 10, 2016; Copenhagen, Denmark.