Travel and VTE
afford it, clinicians can recommend that they use a pair of
compression stockings during their next long flight, Dr.
Carrier said.
“For very high–risk patients, on a case-by-case basis, I
also recommend a prophylactic dose of LMWH,” he said.
“But, more recently, I have been prescribing prophylactic
direct anticoagulants instead of LMWH.”
Do’s and DOACs
The U.S. Food and Drug Administration has approved
five direct oral anticoagulants (DOACs) in recent years:
dabigatran, rivaroxaban, apixaban, edoxaban, and betrixa-
ban. 12 These agents are now a standard of care for the treat-
ment of VTE and are given prophylactically for orthopedic
surgery, but, according to Dr. Kahn, more research about
their use to prevent VTE in at-risk travelers is needed. 3
“It is reasonable to use a DOAC for prevention or as a
prophylactic dose instead of LMWH,” she said, noting
that
T:7.75"
these oral medications are rapid-acting and do not require
S:7"
injection. “However, we have no studies that have looked
at that [option], so we did not include them in [ASH’s]
recommendations,” Dr. Kahn said.
WARNING: CAPILLARY LEAK SYNDROME
Capillary Leak Syndrome (CLS), which may be life-threatening or fatal if not properly
managed, can occur in patients receiving ELZONRIS. Monitor for signs and symptoms of
CLS and take actions as recommended [see Warnings and Precautions].
INDICATIONS AND USAGE
ELZONRIS™ is a CD123-directed cytotoxin for the treatment of blastic plasmacytoid
dendritic cell neoplasm (BPDCN) in adults and in pediatric patients 2 years and older.
CONTRAINDICATIONS
None
WARNINGS AND PRECAUTIONS
Capillary Leak Syndrome
Capillary leak syndrome (CLS), including life-threatening and fatal cases, has been
reported among patients treated with ELZONRIS. In patients receiving ELZONRIS in
clinical trials, the overall incidence of CLS was 55% (52/94), including Grade 1 or 2
in 46% (43/94), Grade 3 in 6% (6/94), Grade 4 in 1% (1/94) and 2 fatal events (2/94,
2%). Common signs and symptoms (incidence ≥ 20%) associated with CLS that were
reported during treatment with ELZONRIS include hypoalbuminemia, edema, weight
gain, and hypotension.
Before initiating therapy with ELZONRIS, ensure that the patient has adequate cardiac
function and serum albumin is greater than or equal to 3.2 g/dL. During treatment
with ELZONRIS, monitor serum albumin levels prior to the initiation of each dose of
ELZONRIS and as indicated clinically thereafter, and assess patients for other signs
or symptoms of CLS, including weight gain, new onset or worsening edema, including
pulmonary edema, and hypotension or hemodynamic instability. See table below for
CLS management guidelines.
CLS Management Guidelines
Time of
Presentation
Prior to first
dose of
ELZONRIS in
cycle 1
CLS
Sign/Symptom
ELZONRIS
Dosing
Management
Serum albumin
< 3.2 g/dL Administer ELZONRIS when serum albumin
≥ 3.2 g/dL.
Serum albumin
< 3.5 g/dL
Serum albumin
reduced by
≥ 0.5 g/dL from
the albumin value
measured prior to
ELZONRIS dosing
initiation of the
current cycle Administer 25g intravenous
albumin (q12h or more
frequently as practical)
until serum albumin is
≥ 3.5 g/dL AND not more
than 0.5 g/dL lower than
the value measured prior
to dosing initiation of the
current cycle.
A predose body
weight that is
increased by
≥ 1.5 kg over the
previous day’s
predose weight
During
ELZONRIS
dosing
Edema, fluid
overload and/or
hypotension
1
Recommended
Action
Administer 25g intravenous
albumin (q12h or more
frequently as practical),
and manage fluid status
as indicated clinically (e.g.,
generally with intravenous
fluids and vasopressors
if hypotensive and with
diuretics if normotensive
or hypertensive), until
body weight increase has
resolved (i.e. the increase
is no longer ≥ 1.5 kg greater
than the previous day’s
predose weight).
Administer 25g intravenous
albumin (q12h, or more
frequently as practical) until
serum albumin is ≥ 3.5 g/dL.
Administer 1 mg/kg
of methylprednisolone
(or an equivalent) per day,
until resolution of CLS
sign/symptom or as
indicated clinically.
Aggressive management
of fluid status and
hypotension if present,
which could include
intravenous fluids and/
or diuretics or other blood
pressure management,
until resolution of CLS
sign/symptom or as
clinically indicated.
One review article looked at the possible role of DOACs
in treatment of travel-related VTE, concluding that DOACs
could be used “to treat travel-related VTE, as there is no
evidence suggesting that it is different from VTE in gen-
eral,” with the exception of patients with active malignancy,
where LMWH is preferred. 13
Similarly, the authors concluded that “there is no
rationale to suggest that DOACs are not effective” for pri-
mary prophylaxis, and more trial data are needed among
very high–risk patients before recommending DOACs.
“In my personal practice, if I think prophylaxis is
Hypersensitivity Reactions
ELZONRIS can cause severe hypersensitivity reactions. In patients receiving
ELZONRIS in clinical trials, hypersensitivity reactions were reported in 46% (43/94)
of patients treated with ELZONRIS and were Grade ≥ 3 in 10% (9/94). Manifestations
of hypersensitivity reported in ≥ 5% of patients include rash, pruritus, stomatitis,
and wheezing. Monitor patients for hypersensitivity reactions during treatment with
ELZONRIS. Interrupt ELZONRIS infusion and provide supportive care as needed if a
hypersensitivity reaction should occur.
Hepatotoxicity
Treatment with ELZONRIS was associated with elevations in liver enzymes. In patients
receiving ELZONRIS in clinical trials, elevations in liver enzymes occurred in 88%
(83/94) of patients, including Grade 1 or 2 in 48% (45/94), Grade 3 in 36% (34/94),
and Grade 4 in 4% (4/94). Monitor alanine aminotransferase (ALT) and aspartate
aminotransferase (AST) prior to each infusion with ELZONRIS. Withhold ELZONRIS
temporarily if the transaminases rise to greater than 5 times the upper limit of normal
and resume treatment upon normalization or when resolved.
ADVERSE REACTIONS
Most common adverse reactions (incidence ≥ 30%) are capillary leak syndrome,
nausea, fatigue, peripheral edema, pyrexia and weight increase. Most common
laboratory abnormalities (incidence ≥ 50%) are decreases in albumin, platelets,
hemoglobin, calcium, and sodium, and increases in glucose, ALT and AST.
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
the clinical trials of another drug and may not reflect the rates observed in practice.
Safety of ELZONRIS was assessed in a single-arm clinical trial that included 94 adults
with newly diagnosed or relapsed/refractory myeloid malignancies, including 58 with
BPDCN, treated with ELZONRIS 12 mcg/kg daily for 5 days of a 21-day cycle. The
overall median number of cycles administered was 2 (range, 1-43), and 4 in patients
with BPDCN (range, 1-43). Two (2%) patients had fatal adverse reaction, both capillary
leak syndrome. Overall, 10 (11%) patients discontinued treatment with ELZONRIS due
to an adverse reaction; the most common adverse reactions resulting in treatment
discontinuation were hepatic toxicities and CLS.
Table below summarizes the common (≥ 10%) adverse reactions with ELZONRIS in
patients with myeloid malignancies. The rate of any given adverse reaction or lab
abnormality was derived from all the reported events of that type.
Adverse Reactions in ≥ 10% of Patients Receiving 12 mcg/kg of ELZONRIS
N=94
All Grades
% Grade ≥ 3
%
Capillary leak syndrome 1 55 9
Hypotension 29 9
Hypertension 15 6
Nausea 49 0
Constipation 23 0
Vomiting 21 0
Diarrhea 20 0
Vascular Disorders
Gastrointestinal disorders
Interrupt
ELZONRIS
dosing until the
relevant CLS
sign/symptom
has resolved 1 .
ELZONRIS administration may resume in the same cycle if all CLS signs/symptoms have resolved and the
patient did not require measures to treat hemodynamic instability. ELZONRIS administration should be held
for the remainder of the cycle if CLS signs/symptoms have not resolved or the patient required measures to
treat hemodynamic instability (e.g., required administration of intravenous fluids and/or vasopressors to treat
hypotension) (even if resolved), and ELZONRIS administration may only resume in the next cycle if all CLS signs/
symptoms have resolved, and the patient is hemodynamically stable.
General disorders and administration
site conditions
Fatigue 45 7
Peripheral edema 43 1
Pyrexia 43 0
Chills 29 1
31 0
Headache 29 0
Dizziness 20 0
24 0
20 18
Back pain 20 2
Pain in extremity 10 2
Investigations
Weight increase
Nervous system disorders
Metabolism and nutrition disorders
Decreased appetite
Blood and lymphatic system disorders
Febrile neutropenia
Musculoskeletal and connective
tissue disorders