FEATURE
warranted, I tell a patient to take the tablets,” Dr. Crowther
said, noting that the literature on the use of prophylactic
DOACs for travel-related VTE is nonexistent.
Dr. Carrier agreed, saying he has seen increasing use of
DOACs instead of injectable LMWH. “It’s all about risks
and benefits. I would estimate the benefit from peace of
mind and reassurance against the risk of bleeding from one
tablet is very small.”
The Provoked vs. Unprovoked Debate
In the rare case when travel-related VTE occurs or is
suspected, questions build. Clinicians must decide wheth-
er the clot was provoked by travel or some other factor.
“This is a controversial but important topic,” Dr.
Carrier explained, “because this decision will make a
difference in whether a patient is bound to long-term
anticoagulation or can stop anticoagulation after three
months. Clinicians have to make a judgment call.”
T:7.75"
For example, if anticoagulation is stopped after three to
S:7"
12
months, patients with unprovoked VTE have a 30-percent
risk of experiencing a recurrent VTE over five years. 14
Determining whether the clot is provoked or
Adverse Reactions in ≥ 10% of Patients Receiving 12 mcg/kg of
ELZONRIS (Cont’d)
N=94
All Grades
% Grade ≥ 3
%
Dyspnea 19 2
Cough 14 0
Epistaxis 14 1
Oropharyngeal pain 12 0
Respiratory, thoracic and mediastinal
disorders
Psychiatric disorders
Insomnia 17 0
Anxiety 15 0
Confusional state 11 0
17 0
Petechiae 10 0
Pruritus 10 0
10 0
Cardiac disorders
Tachycardia
Skin and subcutaneous tissue disorders
Renal and urinary disorders
Hematuria
Capillary leak syndrome defined as any event reported as CLS during treatment with ELZONRIS or the occurrence
of at least 2 of the following CLS manifestations within 7 days of each other: hypoalbuminemia (including albumin
value less than 3.0 g/dL), edema (including weight increase of 5 kg or more), hypotension (including systolic blood
pressure less than 90 mmHg).
1
Table below summarizes the clinically-important laboratory abnormalities that occurred
in ≥ 10% patients with myeloid malignancies treated with ELZONRIS.
Selected Laboratory Abnormalities in Patients Receiving 12 mcg/kg of ELZONRIS
All Grades
% Grade ≥ 3
%
Platelets decrease 67 53
Hemoglobin decrease 60 35
Neutrophils decrease 37 31
Hematology
Chemistry
Glucose increase 87 20
ALT increase 82 30
AST increase 79 37
Albumin decrease 77 0
Calcium decrease 57 2
Sodium decrease 50 10
Potassium decrease 39 4
Phosphate decrease 30 11
Creatinine increase 27 0
Alkaline phosphatase increase 26 1
Potassium increase 21 2
Magnesium decrease 20 0
Magnesium increase 14 3
Bilirubin increase 14 0
Glucose decrease 11 0
Sodium increase 10 0
DRUG INTERACTIONS
No drug-drug interaction studies have been conducted with ELZONRIS.
USE IN SPECIFIC POPULATIONS
Pregnancy
Risk Summary
Based on its mechanism of action, ELZONRIS has the potential for adverse effects on
embryo-fetal development. There are no available data on ELZONRIS use in pregnant
women to inform a drug-associated risk of adverse developmental outcomes.
in the pediatric patients was similar to that seen in the adults. Efficacy for pediatric
patients is extrapolated from the results of STML-401-0114.
Geriatric Use
Of the 94 patients who received ELZONRIS at the labeled dose in STML-401-0114,
23% were 75 years and older. The older patients experienced a higher incidence of
altered mental status (including confusional state, delirium, mental status changes,
dementia, and encephalopathy) than younger patients.
PATIENT COUNSELING INFORMATION
Capillary Leak Syndrome
Advise patients of the risk of capillary leak syndrome (CLS), and to contact their health
care professional for signs and symptoms associated with CLS including new or
worsening edema, weight gain, shortness of breath, and/or hypotension after infusion.
Advise patients to weigh themselves daily [see Warnings and Precautions].
Hypersensitivity
Advise patients of the risk of hypersensitivity reactions, and to contact their
healthcare professional for signs and symptoms associated with hypersensitivity
reactions including rash, flushing, wheezing and swelling of the face [see Warnings
and Precautions].
Hepatic Toxicity
Advise patients to report symptoms that may indicate elevated liver enzymes including
fatigue, anorexia and/or right upper abdominal discomfort [see Warnings and
Precautions].
Contraception
Advise females to avoid pregnancy and to use acceptable contraceptive methods
during ELZONRIS treatment and for at least 1 week after the last dose of ELZONRIS
Lactation
Advise women not to breastfeed [see Use in Specific Populations].
For more detailed information please see full Prescribing Information, including
Boxed WARNING.
To report adverse events, please contact Stemline Therapeutics, Inc. at 1-877-332-7961
or you may report to the FDA at 1-800-FDA-1088 or visit www.fda.gov/medwatch.
Marketed and Distributed by:
Stemline Therapeutics, Inc.
New York, NY 10022
www.stemline.com
US License No. 2088
US-ELZ-1900004
REFERENCES
1. World Thrombosis Day. “Personal stories: Suely Rezende,
MD, PhD.” Accessed February 8, 2019, from http://www.
worldthrombosisday.org/campaign-materials/personal-
stories/suely-rezende/.
2. Kuipers S, Schreijer AJ, Cannegieter SC, et al. Travel and
venous thrombosis: a systematic review. J Intern Med.
2007;262:615-34.
3. Schunemann HJ, Cushman M, Burnett AE, et al. American
Society of Hematology 2018 guidelines for management of
venous thromboembolism: prophylaxis for hospitalized and
nonhospitalized medical patients. Blood Adv. 2018;2:3198-
225.
4. Lapostolle F, Surget V, Borron SW, et al. Severe pulmonary
embolism associated with air travel. N Engl J Med.
2001;345:779-83.
5. Chee YL, Watson HG. Air travel and thrombosis. Br J
Haematol. 2005;130:671-80.
6. Schobersberger W, Fries D, Mittermayr M, et al. Changes of
biochemical markers and functional tests for clot formation
during long-haul flights. Thromb Res. 2002;108:19-24.
7. American Society of Hematology. “Venous Thromboembolic
Disease: Opportunities to Improve Risk Prediction, Treatment,
and Prevention.” Accessed February 8, 2019, from http://
www.hematology.org/Research/Recommendations/
Research-Agenda/3824.aspx.
8. Eichinger S, Hron G, Bialonczyk C, et al. Overweight, obesity,
and the risk of recurrent venous thromboembolism. Arch
Intern Med. 2008;168:1678-83.
9. Clarke MJ, Broderick C, Hopewell S, et al. Compression
stockings for preventing deep vein thrombosis in airline
passengers. Cochrane Database Syst Rev. 2016;9:CD004002.
10. Cesarone MR, Belcaro G, Nicolaides AN, et al. Venous
thrombosis from air travel: the LONFLIT3 study--prevention
with aspirin vs low-molecular-weight heparin (LMWH)
in high-risk subjects: a randomized trial. Angiology.
2003;54(5):531-9.
11. Centers for Disease Control and Prevention. “Venous
Thromboembolism (Blood Clots).” Accessed February 6, 2019,
from https://www.cdc.gov/ncbddd/dvt/travel.html.
12. Steuber T. The role of direct oral anticoagulants in the
management of venous thromboembolism. Am J Manag Care.
2017;23:S383-90.
13. Chamnanchanunt S, Rojnuckarin P. Direct oral anticoagulants
and travel-related venous thromboembolism. Open Med.
2018;13:575-82.
14. Kearon C, Akl EA. Duration of anticoagulant therapy for
deep vein thrombosis and pulmonary embolism. Blood.
2014;123:1794-1801.
10.
S
Treatment-Emergent
Laboratory Abnormalities
unprovoked should be a simple process, but, in the set-
ting of air travel, the question becomes more complicated,
according to Dr. Crowther.
“Air travel is not like a recent fracture, where risk is clear,”
he said. “Air travel–related VTE generally is considered
provoked, but in the setting of a weak risk factor.”
Dr. Kahn agreed. “To say that air travel represents a
provoked episode of VTE doesn’t seem to be that logical
to those who work in the field, but neither does calling it
unprovoked. Travel-related VTE falls in that gray zone we
call ‘weakly provoked.’”
It is important to determine whether
patients have a comorbidity, clinical risk
factors, or other marker that made them
Animal reproduction or developmental toxicity studies have not been conducted with
more likely to experience thrombosis
tagraxofusp-erzs. Advise pregnant women of the potential risk to the fetus.
than the person sitting in the seat next to
The estimated background risk of major birth defects and miscarriage for the indicated
them, Dr. Kahn explained.
population is unknown. All pregnancies have a risk of birth defect, loss, or other adverse
outcomes. In the US general population, the estimated background risk of major birth
“That information influences the
defects and miscarriage in clinically recognized pregnancies is 2% to 4%, and 15% to
duration
of treatment for the episode
20%, respectively.
of
VTE,
and
this varies a lot across
Lactation
Risk Summary
practitioners and depends on whether
No data are available regarding the presence of ELZONRIS in human milk, the effects
they feel the idea of ‘weakly provoked’
on the breastfed child, or the effects on milk production. Because of the potential for
serious adverse reactions in breastfed children from ELZONRIS, breast feeding is not
falls more into a category of provoked
recommended during treatment and for 1 week after the last dose.
or unprovoked,” Dr. Kahn said. “If the
Females and Males of Reproductive Potential
decision is made to stop anticoagula-
Based on its mechanism of action, ELZONRIS may cause fetal harm when administered
to a pregnant woman.
tion after three months, one thing we
Pregnancy Testing
would usually do in a patient with
Conduct pregnancy testing in females of reproductive potential within 7 days prior to
travel-related thrombosis is to offer
initiating ELZONRIS treatment.
prophylaxis to prevent another episode
Contraception
Advise females to use acceptable contraceptive methods during ELZONRIS treatment
during future travel.”
and for at least 1 week after the last dose of ELZONRIS.
With so many differing opinions
Pediatric Use
about
how much air travel contributes
The safety and effectiveness of ELZONRIS for treatment of BPDCN have been
established in pediatric patients 2 years of age and older (no data for pediatric
to VTE risk, however, definitive recom-
patients less than 2 years of age). Use of ELZONRIS in these age groups is supported
mendations about preventing travel-
by evidence from an adequate and well-controlled study of ELZONRIS in adults with
BPDCN and additional safety data from three pediatric patients with BPDCN, including
related VTE are still up in the air.
1 child (2 years to < 12 years old) and 2 adolescents (12 years to < 17 years old),
—By Leah Lawrence ●
treated with ELZONRIS at the recommended dosage. The safety profile of ELZONRIS
ASH Clinical News
39