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Masitinib Improves Symptom Burden, Responses
in Patients with Severe Systemic Mastocytosis
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.”
skin events and typically manageable with dose reductions.
Masitinib, a selective oral tyrosine kinase inhibitor (TKI) targeting wild-type KIT, LYN, and FYN, reduced the severity of a Long-term safety assessment revealed comparable rates of
diverse range of symptoms in patients with severely symptom- AEs between both treatment arms, with no deaths or lifeREFERENCE
Hermine O, Chandesris MO, Livideanu CB, et al. Masitinib for the treatment of severely sympthreatening AEs in the masitinib arm.
atic indolent or smoldering systemic mastocytosis (ISM or
tomatic indolent and smoldering systemic mastocytosis: a randomized, placebo-controlled,
Severe
AEs
with
a
greater
than
four
percent
difference
SSM) who were unresponsive to other treatments, according
international, phase 3 study. Abstract S828. Presented at the EHA 21st Congress, June 10, 2016;
between treatment arms were: diarrhea (9.8%), rash (5.7%),
Copenhagen, Denmark.
to results from a randomized phase III
S:6.75”
trial presented by Olivier Hermine,
MD, PhD, from the University of Paris
Descartes, at the European Hematology
Association’s 21st Congress.
BOSULIF is indicated for the treatment of adult patients with chronic, accelerated, or blast phase Philadelphia
Mastocytosis is designated as an orchromosome–positive (Ph+) chronic myelogenous leukemia (CML) with resistance or intolerance to prior therapy.
phan disease by the U.S. Food and Drug
Administration and is characterized by
an abnormal proliferation or activation
In the treatment of adult patients with Ph+ CML with resistance or intolerance to prior therapy
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
( b o s u t inib)
treatment option for these patients
… with both efficacy and safety data
indicating a possibility for effective longterm management of this difficult-totreat 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
Bosutinib (BOSULIF®) is recommended by the NCCN Clinical Practice Guidelines in
eight weeks to 96 weeks post-treatment
Oncology
(NCCN Guidelines®) as a treatment option for patients with CML in need
initiation.
of 2nd- or later-line TKI therapy.1
Masitinib resulted in a significant
improvement over placebo in rates
of cumulative response (the study’s
Study design: BOSULIF 500 mg once-daily treatment was studied in a single-arm, Phase 1/2, open-label, multicenter
primary endpoint; defined as a ≥75%
trial (N=546) in patients with CP, AP, or BP CML in second line (after imatinib) or in third line (after imatinib followed by
improvement in at least one severe basedasatinib and/or nilotinib). Of the 546 patients enrolled, 73% were imatinib resistant and 27% were imatinib intolerant.2
line symptom): 18.7 percent versus 7.4
AP=accelerated phase; BP=blast phase; CP=chronic phase.
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, masihepatic enzyme tests monthly for the first 3 months and as clinically indicated.
IMPORTANT SAFETY INFORMATION
tinib-treated patients had lower tryptase
In patients with transaminase elevations, monitor liver enzymes more
Contraindication: History of hypersensitivity to BOSULIF. Reactions have
levels relative to baseline, compared
frequently. Drug-induced liver injury has occurred. Withhold, dose reduce, or
included anaphylaxis. Anaphylactic shock occurred in less than 0.2% of treated
with patients who received placebo:
discontinue BOSULIF as necessary. In patients with mild, moderate, or severe
patients in clinical trials.
18.0 percent decrease in the masitinib
hepatic impairment, the recommended starting dose is 200 mg daily.
arm versus a 2.2 percent increase in the
Gastrointestinal Toxicity: Diarrhea, nausea, vomiting, and abdominal pain
Renal Toxicity: An on-treatment decline in estimated glomerular filtration
placebo arm (p<0.001).
can occur. In the clinical trial, median time to onset for diarrhea was 2 days,
rate h as occurred in patients treated with BOSULIF. Monitor renal function
Masitinib also led to significantly
median duration was 1 day, and median number of episodes per patient was 3
at baseline and during therapy, with particular attention to patients with
better clearance of urticaria pigmentosa
(range 1-221). Monitor and manage patients using standards of care, including
preexisting renal impairment or risk factors. Consider dose adjustment
in patients who received the study drug
antidiarrheals, antiemetics, and/or fluid replacement. Withhold, dose reduce,
in patients with baseline and treatment emergent renal impairment. The
compared with placebo (p=0.02).
or discontinue BOSULIF as necessary.
recommended starting doses for patients with severe renal impairment
Treatment with masitinib appeared
Myelosuppression: Thrombocytopenia, anemia, and neutropenia can occur.
(CrCL
<30 mL/min) or moderate renal impairment (CrCL 30-50 mL/min)
safe and consistent with the drug’s
Perform complete blood counts weekly for the first month and then monthly
are
300
mg and 400 mg daily, respectively.
known adverse events (AEs); toxicities
or
as
clinically
indicated.
Withhold,
dose
reduce,
or
discontinue
BOSULIF
were predominantly gastrointestinal or
Fluid Retention: Fluid retention can occur and may cause pericardial effusion,
Everyone has a distinct profile
Consider your patient.Consider BOSULIF.
as necessary.
Hepatic Toxicity: Twenty percent of patients experienced an increase in either
ALT or AST. Liver enzyme elevation usually occurs early in treatment. Perform
28
ASH Clinical News
pleural effusion, pulmonary edema, and/or peripheral edema. Monitor
and manage patients using standards of care. Interrupt, dose reduce, or
discontinue BOSULIF as necessary.
B:15.5”
T:15.25”
G:.5”