On Location ASH Annual Meeting
following haplo-HCT for [patients
with] acute leukemia,” the authors
concluded, “with potential implica-
tions for future donor selection
algorithms in haplo-HCT.”
The findings of the study were
limited by its retrospective nature,
and other studies are needed to
confirm the results and determine
the underlying factors that might
contribute to poorer post-HCT
Idasanutlin Well Tolerated in Patients
With Polycythemia Vera and Essential
Thrombocythemia
survival with older donors.
The authors report financial
relationships with Celgene, Novar-
tis, Jazz Pharmaceuticals, Bristol-
Myers Squibb, and Janssen.
REFERENCE
Canaani J, Savani BN, Labopin M, et al. Donor age
determines outcome in acute leukemia patients
undergoing haploidentical hematopoietic cell
transplantation. Abstract #850. Presented at the 2017
American Society of Hematology Annual Meeting,
December 11, 2017; Atlanta, GA.
The MDM2 antagonist idasanutlin was well
tolerated and demonstrated “clear clinical
activity” in patients with polycythemia vera
(PV) and essential thrombocythemia (ET)
VONVENDI [von Willebrand factor (Recombinant)]
Brief Summary of Prescribing Information. Please see package insert for full Prescribing Information
INDICATIONS AND USAGE
VONVENDI [von Willebrand factor (Recombinant)] is a recombinant
von Willebrand factor indicated for on-demand treatment and control
of bleeding episodes in adults (age 18 and older) diagnosed with von
Willebrand disease.
The safety profile of VONVENDI was evaluated in three prospective,
multicenter trials; two were conducted in subjects with von Willebrand
disease (n=66) and one was conducted in subjects with hemophilia
A (n=12). The adverse reactions reported in the two von Willebrand
disease trials are listed in Table 1.
Table 1:
CONTRAINDICATIONS
VONVENDI is contraindicated in patients who have had life-threatening
hypersensitivity reactions to VONVENDI or constituents of the product
(tri-sodium citrate-dihydrate, glycine, mannitol, trehalose-dihydrate,
polysorbate 80, and hamster or mouse proteins).
WARNINGS AND PRECAUTIONS
Embolism and Thrombosis
Thromboembolic reactions, including disseminated intravascular
coagulation (DIC), venous thrombosis, pulmonary embolism,
myocardial infarction, and stroke, can occur, particularly in patients
with known risk factors for thrombosis. Monitor for early signs and
symptoms of thrombosis such as pain, swelling, discoloration, dyspnea,
cough, hemoptysis, and syncope.
Summary of Adverse Reactions in Patients with
von Willebrand Disease a
System Organ
Class (SOC) Adverse Reaction
Cardiac Disorders Gastrointestinal
Disorders
Skin and
Subcutaneous
Tissues Disorders
Hypersensitivity Reactions
Hypersensitivity reactions, including anaphylaxis, may occur.
Symptoms can include anaphylactic shock, generalized urticaria,
angioedema, chest tightness, hypotension, shock, lethargy, nausea,
vomiting, paresthesia, pruritus, restlessness, wheezing and/or acute
respiratory distress. If signs and symptoms of severe allergic reactions
occur, immediately discontinue administration of VONVENDI and
provide appropriate supportive care. Vascular Disorder
VONVENDI contains trace amounts of mouse immunoglobulin
G (MuIgG) and hamster proteins less than or equal to 2 ng/
IU VONVENDI. Patients treated with this product may develop
hypersensitivity reactions to non-human mammalian proteins. Investigations
In patients with high levels of inhibitors to VWF or factor VIII,
VONVENDI therapy may not be effective and infusion of this protein
may lead to severe hypersensitivity reactions. Since inhibitor antibodies
can occur concomitantly with anaphylactic reactions, evaluate patients
experiencing an anaphylactic reaction for the presence of inhibitors.
Monitoring Laboratory Tests
• Monitor plasma levels of VWF:RCo and factor VIII activities in
patients receiving VONVENDI to avoid sustained excessive von
Willebrand factor and/or factor VIII activity levels, which may
increase the risk of thrombotic events, particularly in patients with
known clinical or laboratory risk factors.
• Monitor for development of von Willebrand factor and/or factor
VIII inhibitors when suspected. Perform appropriate inhibitor assays
to determine if von Willebrand factor and/or factor VIII inhibitors
are present if bleeding is not controlled with the expected dose of
VONVENDI.
ADVERSE REACTIONS
The most common adverse reaction observed in ≥2% of subjects in
clinical trials (n=66) was generalized pruritus.
Clinical Trials Experience
Because clinical trials are conducted under widely varying conditions,
adverse reaction rates observed in the clinical trials of a drug cannot be
directly compared to rates in clinical trials of another drug and may not
reflect the rates observed in clinical practice.
Number of Infusions
(%)
(n=355)
Tachycardia 1 (1.52%) 1 (0.28%)
Nausea 1 (1.52%) 1 (0.28%)
1 (1.52%) 1 (0.28%)
1 (1.52%) 1 (0.28%)
Generalized
pruritus 2 (3.03%) 2 (0.56%)
Hot flush 1 (1.52%) 1 (0.28%)
Hypertension 1 (1.52%) 2 (0.56%)
Dizziness 1 (1.52%) 1 (0.28%)
Dysgeusia 1 (1.52%) 1 (0.28%)
Tremor 1 (1.52%) 1 (0.28%)
Heart rate increase 1 (1.52%) 1 (0.28%)
Electrocardiogram
T wave inversions 1 (1.52%) 1 (0.28%)
Infusion site
General Disorders paresthesia
and Administration
Site Conditions
Chest discomfort
In patients requiring frequent doses of VONVENDI with recombinant
factor VIII, monitor plasma levels for FVIII:C activity because
an excessive rise in factor VIII levels can increase the risk of
thromboembolic complications.
Neutralizing Antibodies
Neutralizing antibodies (inhibitors) to von Willebrand factor and/
or factor VIII can occur. If the expected plasma levels of VWF activity
(VWF:RCo) are not attained, perform an appropriate assay to determine
if anti-VWF or anti-FVIII inhibitors are present. Consider other
therapeutic options and direct the patient to a physician with experience
in the care of either von Willebrand disease or hemophilia A.
Number of Subjects
(%)
(n=66)
Nervous System
Disorders
a
This trial was done using ADVATE [Antihemophilic factor (Recombinant)], a recombinant factor VIII.
Immunogenicity
The immunogenicity of VONVENDI was assessed in clinical trials by
assessing the development of neutralizing antibodie