ASH News Daily 2013 - Day 2 - (Page B-6)
ASH News Daily
Page B-6
Sunday, December 8, 2013
®
ASH Applauds the 2013 Minority Graduate Student
Abstract Achievement Award Recipients
T
he Minority Graduate Student Abstract Achievement
Award is part of the ASH
Abstract Achievement Award program. The Minority Graduate Student Abstract Achievement Award
program is meant to encourage minority graduate students in the field
of hematology and is part of the
broader minority recruitment initiative at ASH, which also includes the
Minority Medical Student Award
Program (MMSAP) and the ASH-
Harold Amos Medical Faculty Development Program (ASH-AMFDP)
in partnership with the Robert Wood
Johnson Foundation.
The goal of the Minority Graduate Student Abstract Achievement
Award is to attract and/or retain
minority PhD students to the field of
hematology through the ASH annual meeting. At this meeting, students
will have the opportunity to hear
the latest advances in hematologyrelated research and interact with
ASH leadership, senior researchers,
and minority physicians, scientists,
and students. These awards are presented to select graduate students
to acknowledge their accomplishments in the field of hematology.
Adam Bush, BS
University of Southern California
Abstract #2210
111. Hemoglobinopathies, excluding Thalassemia: Poster II
Today, 6:30 to 8:30 p.m.
exposures at the recommended doses for patients with HL and sALCL. If this drug is used during pregnancy,
or if the patient becomes pregnant while receiving the drug, the patient should be apprised of the potential
hazard to the fetus.
Adverse reactions
Brief Summary of Prescribing Information
(see Package Insert for full Prescribing Information)
WARNING: PROGRESSIVE MULTIFOCAL LEUKOENCEPHALOPATHY (PML)
JC virus infection resulting in PML and death can occur in patients
receiving ADCETRIS.
Indications and usage
These indications are based on response rate. There are no data available demonstrating improvement
in patient reported outcomes or survival with ADCETRIS.
ADCETRIS® (brentuximab vedotin) is indicated for treatment of patients with Hodgkin lymphoma (HL) after
failure of autologous stem cell transplant (ASCT) or after failure of at least two prior multi-agent chemotherapy
regimens in patients who are not ASCT candidates.
ADCETRIS is indicated for treatment of patients with systemic anaplastic large cell lymphoma (sALCL)
after failure of at least one prior multi-agent chemotherapy regimen.
Dosage and administration
General dosing information
The recommended dose is 1.8 mg/kg administered only as an intravenous infusion over 30 minutes every
3 weeks. The dose for patients weighing greater than 100 kg should be calculated based on a weight of
100 kg. The recommended starting dose in patients with severe renal impairment (creatinine clearance
<30 mL/min) is 1.2 mg/kg administered only as an intravenous infusion over 30 minutes every 3 weeks.
The recommended starting dose in patients with hepatic impairment is 1.2 mg/kg administered only as an
intravenous infusion over 30 minutes every 3 weeks. Do not administer as an intravenous push or bolus.
Continue treatment until disease progression or unacceptable toxicity.
Dose modification
Peripheral Neuropathy: For new or worsening Grade 2 or 3 neuropathy, dosing should be held until
neuropathy improves to Grade 1 or baseline and then restarted at 1.2 mg/kg. For Grade 4 peripheral
neuropathy, ADCETRIS should be discontinued.
ADCETRIS was studied as monotherapy in 160 patients in two phase 2 trials. Across both trials, the most
common adverse reactions (≥10%), regardless of causality, were neutropenia, anemia, thrombocytopenia,
lymphadenopathy, peripheral sensory neuropathy, peripheral motor neuropathy, headache, dizziness, fatigue,
pyrexia, chills, pain, edema peripheral, upper respiratory tract infection, nausea, diarrhea, abdominal pain,
vomiting, constipation, rash, pruritus, alopecia, night sweats, dry skin, cough, dyspnea, oropharyngeal pain,
arthralgia, myalgia, back pain, pain in extremity, muscle spasms, insomnia, anxiety, decreased appetite and
weight decreased.
ADCETRIS was studied in 102 patients with HL in a single arm clinical trial in which the recommended
starting dose and schedule was 1.8 mg/kg intravenously every 3 weeks. Median duration of treatment was
27 weeks (range, 3 to 56 weeks). The most common adverse reactions (≥20%), regardless of causality,
were neutropenia, peripheral sensory neuropathy, fatigue, upper respiratory tract infection, nausea, diarrhea,
anemia, pyrexia, thrombocytopenia, rash, abdominal pain, cough, and vomiting. The most common serious
adverse reactions experienced by patients with HL include peripheral motor neuropathy (4%), abdominal pain
(3%), pulmonary embolism (2%), pneumonitis (2%), pneumothorax (2%), pyelonephritis (2%), and pyrexia (2%).
ADCETRIS® (brentuximab vedotin) was studied in 58 patients with sALCL in a single arm clinical trial in which
the recommended starting dose and schedule was 1.8 mg/kg intravenously every 3 weeks. Median duration
of treatment was 24 weeks (range, 3 to 56 weeks). The most common adverse reactions (≥20%), regardless
of causality, were neutropenia, anemia, peripheral sensory neuropathy, fatigue, nausea, pyrexia, rash,
diarrhea, and pain. The most common serious adverse reactions experienced by patients with sALCL were
septic shock (3%), supraventricular arrhythmia (3%), pain in extremity (3%), and urinary tract infection (3%).
Drug interactions
In vitro data indicate that monomethyl auristatin E (MMAE) is a substrate and an inhibitor of CYP3A4/5.
In vitro data indicate that MMAE is also a substrate of the efflux transporter P-glycoprotein (P-gp).
Effect of other drugs on ADCETRIS
CYP3A4 Inhibitors/Inducers: MMAE is primarily metabolized by CYP3A. Co-administration of ADCETRIS with
ketoconazole, a potent CYP3A4 inhibitor, increased exposure to MMAE by approximately 34%. Patients who
are receiving strong CYP3A4 inhibitors concomitantly with ADCETRIS should be closely monitored for adverse
reactions. Co-administration of ADCETRIS with rifampin, a potent CYP3A4 inducer, reduced exposure to
MMAE by approximately 46%.
P-gp Inhibitors: Co-administration of ADCETRIS with P-gp inhibitors may increase exposure to MMAE.
Patients who are receiving P-gp inhibitors concomitantly with ADCETRIS should be closely monitored for
adverse reactions.
Effect of ADCETRIS on other drugs
Neutropenia: The dose of ADCETRIS should be held for Grade 3 or 4 neutropenia until resolution to baseline
or Grade 2 or lower. G-CSF support should be considered for subsequent cycles in patients who experience
Grade 3 or 4 neutropenia. In patients with recurrent Grade 4 neutropenia despite the use of G-CSF support,
discontinuation or dose reduction of ADCETRIS to 1.2 mg/kg may be considered.
Co-administration of ADCETRIS did not affect exposure to midazolam, a CYP3A4 substrate. MMAE does
not inhibit other CYP enzymes at relevant clinical concentrations. ADCETRIS is not expected to alter the
exposure to drugs that are metabolized by CYP3A4 enzymes.
Contraindications
Pregnancy
Use in specific populations
Warnings and precautions
Pregnancy Category D.
Risk Summary
There are no adequate and well-controlled studies with ADCETRIS in pregnant women. However, based on
its mechanism of action and findings in animals, ADCETRIS can cause fetal harm when administered to a
pregnant woman. Brentuximab vedotin caused embryo-fetal toxicities in animals at maternal exposures that
were similar to human exposures at the recommended doses for patients with HL and sALCL. If this drug is
used during pregnancy, or if the patient becomes pregnant while receiving this drug, the patient should be
apprised of the potential hazard to the fetus.
ADCETRIS treatment causes a peripheral neuropathy that is predominantly sensory. Cases of peripheral
motor neuropathy have also been reported. ADCETRIS-induced peripheral neuropathy is cumulative.
In the HL and sALCL clinical trials, 54% of patients experienced any grade of neuropathy. Of these patients,
49% had complete resolution, 31% had partial improvement, and 20% had no improvement. Of the patients
who reported neuropathy, 51% had residual neuropathy at the time of their last evaluation. Monitor patients
for symptoms of neuropathy, such as hypoesthesia, hyperesthesia, paresthesia, discomfort, a burning
sensation, neuropathic pain or weakness. Patients experiencing new or worsening peripheral neuropathy
may require a delay, change in dose, or discontinuation of ADCETRIS.
Animal Data
In an embryo-fetal developmental study, pregnant rats received 2 intravenous doses of 0.3, 1, 3, or 10 mg/kg
brentuximab vedotin during the period of organogenesis (once each on Pregnancy Days 6 and 13). Druginduced embryo-fetal toxicities were seen mainly in animals treated with 3 and 10 mg/kg of the drug and
included increased early resorption (≥99%), post-implantation loss (≥99%), decreased numbers of live
fetuses, and external malformations (i.e., umbilical hernias and malrotated hindlimbs). Systemic exposure
in animals at the brentuximab vedotin dose of 3 mg/kg is approximately the same exposure in patients with
HL or sALCL who received the recommended dose of 1.8 mg/kg every three weeks.
Infusion reactions
Nursing mothers
Pulmonary toxicity: Concomitant use of ADCETRIS and bleomycin is contraindicated due to pulmonary
toxicity. In a clinical trial that studied ADCETRIS with bleomycin as part of a combination regimen, the rate
of non-infectious pulmonary toxicity was higher than the historical incidence reported with ABVD (adriamycin,
bleomycin, vinblastine, dacarbazine). Patients typically reported cough and dyspnea. Interstitial infiltration
and/or inflammation were observed on radiographs and computed tomographic imaging of the chest. Most
patients responded to corticosteroids.
Peripheral neuropathy
Infusion-related reactions, including anaphylaxis, have occurred with ADCETRIS. Monitor patients during
infusion. If anaphylaxis occurs, immediately and permanently discontinue administration of ADCETRIS
and administer appropriate medical therapy. If an infusion-related reaction occurs, the infusion should
be interrupted and appropriate medical management instituted. Patients who have experienced a prior
infusion-related reaction should be premedicated for subsequent infusions. Premedication may include
acetaminophen, an antihistamine and a corticosteroid.
Hematologic toxicities
Grade 3 or Grade 4 anemia, thrombocytopenia, and prolonged (≥1 week) severe neutropenia can occur with
ADCETRIS. Febrile neutropenia has been reported with treatment with ADCETRIS. Complete blood counts
should be monitored prior to each dose of ADCETRIS and more frequent monitoring should be considered
for patients with Grade 3 or 4 neutropenia. Patients should be closely monitored for fever. If Grade 3 or 4
neutropenia develops, manage by G-CSF support, dose delays, reductions, or discontinuations.
Serious infections and opportunistic infections
Serious infections and opportunistic infections such as pneumonia, bacteremia, and sepsis/septic shock
(including fatal outcomes) have been reported in patients treated with ADCETRIS. Patients should be closely
monitored during treatment for the emergence of possible bacterial, fungal or viral infections.
Tumor lysis syndrome
Tumor lysis syndrome may occur. Patients with rapidly proliferating tumor and high tumor burden may be at
increased risk of tumor lysis syndrome. Monitor closely and take appropriate measures.
Progressive multifocal leukoencephalopathy
JC virus infection resulting in PML and death has been reported in ADCETRIS-treated patients. In addition
to ADCETRIS therapy, other possible contributory factors include prior therapies and underlying disease
that may cause immunosuppression.
Consider the diagnosis of PML in any patient presenting with new-onset signs and symptoms of central
nervous system abnormalities. Evaluation of PML includes, but is not limited to, consultation with a
neurologist, brain MRI, and lumbar puncture or brain biopsy. Hold ADCETRIS dosing for any suspected
case of PML and discontinue ADCETRIS dosing if a diagnosis of PML is confirmed.
It is not known whether brentuximab vedotin is excreted in human milk. Because many drugs are excreted in
human milk and because of the potential for serious adverse reactions in nursing infants from ADCETRIS a
decision should be made whether to discontinue nursing or to discontinue the drug, taking into account the
importance of the drug to the mother.
Pediatric use
The safety and effectiveness of ADCETRIS have not been established in the pediatric population. Clinical trials
of ADCETRIS included only 9 pediatric patients and this number is not sufficient to determine whether they
respond differently than adult patients.
Geriatric use
Clinical trials of ADCETRIS did not include sufficient numbers of patients aged 65 and over to determine
whether they respond differently from younger patients. Safety and efficacy have not been established.
Renal impairment
The kidney is a route of excretion for MMAE. A study evaluated the pharmacokinetics of brentuximab vedotin
and MMAE after the administration of 1.2 mg/kg of ADCETRIS to patients with mild (n=4), moderate (n=3)
and severe (n=3) renal impairment. Compared to patients with normal renal function, MMAE exposure
increased approximately 1.9-fold in patients with severe renal impairment (creatinine clearance <30 mL/min).
Patients with severe renal impairment should be closely monitored for adverse reactions.
Hepatic impairment
The liver is a route of clearance for MMAE. A study evaluated the pharmacokinetics of brentuximab vedotin
and MMAE after the administration of 1.2 mg/kg of ADCETRIS to patients with mild (Child-Pugh A; n=1),
moderate (Child-Pugh B; n=5) and severe (Child-Pugh C; n=1) hepatic impairment. Compared to patients
with normal hepatic function, MMAE exposure increased approximately 2.3-fold in patients with hepatic
impairment. Patients with hepatic impairment should be closely monitored for adverse reactions.
Overdosage
There is no known antidote for overdosage of ADCETRIS. In case of overdosage, the patient should be closely
monitored for adverse reactions, particularly neutropenia, and supportive treatment should be administered.
Stevens-Johnson syndrome
Stevens-Johnson syndrome has been reported with ADCETRIS. If Stevens-Johnson syndrome occurs,
discontinue ADCETRIS and administer appropriate medical therapy.
Embryo-fetal toxicity
There are no adequate and well-controlled studies of ADCETRIS in pregnant women. However, based
on its mechanism of action and findings in animals, ADCETRIS can cause fetal harm when administered
to a pregnant woman. Brentuximab vedotin caused embryo-fetal toxicities, including significantly decreased
embryo viability and fetal malformations, in animals at maternal exposures that were similar to human
15287_sgn35_fa2_golf_and.indd 3
ADCETRIS and its logo, SeaGen Secure and its logo, Seattle Genetics
and are US registered trademarks of Seattle Genetics, Inc.
© 2013 Seattle Genetics, Inc., Bothell, WA 98021
All rights reserved. Printed in USA USP/BVP/2013/0041c
10/30/13 1:34 PM
Hall E (Ernest N. Morial Convention Center)
Jason Conage-Pough
Emory University
Abstract #4446
652. Myeloma: Pathophysiology
and Pre-Clinical Studies, excluding
Therapy: Poster III
Monday, December 9, 6:00 to 8:00
p.m.
Hall G (Ernest N. Morial Convention Center)
Norma Iris Rodriguez-Malave, BS
University of California, Los
Angeles
Abstract #3730
602. Disordered Gene Expression in Hematologic Malignancy,
including Disordered Epigenetic
Regulation: Poster III
Monday, December 9, 6:00 to 8:00
p.m.
Hall E (Ernest N. Morial Convention Center)
Colles Price
University of Chicago
Abstract #3740
602. Disordered Gene Expression in Hematologic Malignancy,
including Disordered Epigenetic
Regulation: Poster III
Monday, December 9, 6:00 to 8:00
p.m.
Hall E (Ernest N. Morial Convention Center)
VTP
«« From Page B-4
established for routine diagnostic
work, one run per week as a start.
Cases are low-grade FL, adenocarcinoma of lung EGFR, and breast carcinoma Her2/neu."
- 2011 participant from Iraq
"Since I have returned from my
training, we have started MRD analysis with flow cytometry. Already 5
cases have been completed, in addition to about 20 normal samples of
blood/bone marrow. We are also in
the validation phase for EMA studies for hereditary spherocytosis."
- 2010 participant from India
"My training was on transfusion
medicine and coagulation, thus the
improvements made in my centre
include: improvement of our blood
bank with installation of facilities for
electronic crossmatch, the teaching
of residents on aspects of transfusion medicine and coagulation, and
installment and use of an apheresis
machine for both therapeutic and
donor apheresis"
- 2009 Participant from Nigeria
Table of Contents for the Digital Edition of ASH News Daily 2013 - Day 2
Table of Contents
ASH News Daily 2013 - Day 2
https://www.nxtbookmedia.com