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 ). 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 .”
Reference
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 .
Clotting Factor Deficiencies Associated With Excess Bleeding Risk , Regardless of Factor Levels
Women who have or are carriers for factor VIII ( FVIII ) or factor IX ( FIX ) deficiency often report excessive bleeding , though it is unclear how bleeding risk may vary among females with different factor levels and those with type 1 von Willebrand disease ( vWD ).
“ Hemophilia A and B carriers with normal factor levels are at risk for excessive bleeding , regardless of their factor level , and warrant evaluation by a hematologist ,” Robert F . Sidonio Jr ., MD , from Emory University in Atlanta , Georgia , and lead author of the study , told ASH Clinical News . “ Our objective was to further characterize the bleeding tendencies in hemophilia A and B carriers and females with type 1 vWD enrolled in a large national dataset .”
Using data from the Universal Data Collection ( UDC ) project , which was created to monitor bleeding events among women with inherited bleeding disorders , Dr . Sidonio and colleagues conducted a cross-sectional study of women with FVIII or FIX deficiency or type 1 vWD . Results were presented at the Thrombosis and Hemostasis Societies of North America 2016 Summit .
The researchers collected data about the diagnosis subtype , demographics , and bleeding history ( including oral , joint , skin , central nervous system , gastrointestinal , post-surgical , muscle , and heavy menstrual bleeding and bruising ) of 551 women enrolled at 23 hemophilia centers between 2009 and 2011 .
Seventy-three patients had FVIII / FIX deficiencies and 338 had type 1 vWD . Patients ’ FVIII / FIX deficiency was defined according to severity : severe / moderate ( ≤5 %), mild ( 5-40 %), and
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