ASH News Daily 2017 - Issue 3 - B-25

ASH News Daily

Monday, December 11, 2017

Page B-25
®

career-

Dan Landau, MD, PhD
Dr. Landau is an assistant professor of medicine, physiology,
and biophysics at the Weill Cornell
Medical College, as well as a core
member of the New York Genome
Center. He earned his medical degree from Tel Aviv University and
his PhD from the Paris Diderot
University. He completed clinical
training in hematology and medical oncology at Yale and pursued
research training in cancer genomics at the Dana-Farber Cancer Institute and the Broad Institute of
Harvard and MIT. His laboratory
T:7"
develops computational
and ex-

enhancemenT
awardS

ASH Scholars
«« From Page B-24

Kim's research goal is to establish
a specialized translational program
to better understand the hematopoietic system and to contribute to the
development of safe and effective
strategies to cure HIV/AIDS and
cancers.

The following table summarizes shifts in selected chemistry abnormalities by treatment arm for patients
treated in ALFA-0701.
ALFA-0701 - Chemistry Laboratory Values: Shifts in Subjects with Baseline Grade 2 or Lower Values
MYLOTARG +
Daunorubicin + Cytarabine

Laboratory Abnormality

Hypophosphatemia
Hypokalemia
Hyponatremia
Alkaline phosphatase increased
Aspartate aminotransferase increased
Alanine aminotransferase increased
Blood bilirubin increased

Daunorubicin + Cytarabine

Subjects (n)
with baseline
Grade less
than or equal
to 2

Progressed to
Grade greater
than or equal
to 3 (n, %)

Subjects (n)
with baseline
Grade less
than or
equal
to 2

Progressed to
Grade greater
than or equal
to 3 (n, %)

117
127
129
120
126
124
119

75 (64%)
73 (57%)
57 (44%)
16 (13%)
18 (14%)
13 (10%)
9 (8%)

127
133
134
128
132
132
126

52 (41%)
41 (31%)
36 (27%)
7 (5%)
11 (8%)
20 (15%)
5 (4%)

Monotherapy for Newly-Diagnosed CD33-positive AML
The safety evaluation of MYLOTARG (6 mg/m2 then 3 mg/m2, with 7 days between the doses) as monotherapy is
based on a randomized, open-label, Phase 3 trial of MYLOTARG (N=118) versus best supportive care (BSC) (N=119)
in patients with previously untreated AML who were considered ineligible for intensive chemotherapy in Study
AML-19. The overall incidence of any Grade adverse reactions reported in AML-19 was 87% in the MYLOTARG arm
and 90% in the BSC arm. The incidence of Grade greater than or equal to 3 adverse reactions was 61% in the
MYLOTARG arm and 68% in the BSC arm. Death due to any Adverse Event was reported in the MYLOTARG arm of
19 (17%) compared to the BSC arm of 23 (20%).
Selected Adverse Reactions in AML-19
MYLOTARG
n=111
Any Grade

Grade ≥ 3

Any Grade

Grade ≥ 3

57 (51%)
51 (46%)
49 (44%)
31 (28%)
28 (25%)
20 (18%)
18 (16%)
7 (6%)

8 (7%)
13 (12%)
39 (35%)
7 (6%)
14 (13%)
20 (18%)
4 (4%)
4 (4%)

52 (46%)
69 (61%)
48 (42%)
37 (33%)
34 (30%)
27 (24%)
17 (15%)
9 (8%)

7 (6%)
24 (21%)
39 (34%)
16 (14%)
14 (12%)
27 (24%)
7 (6%)
5 (4%)

Monotherapy for Relapsed or Refractory CD33-positive AML
The adverse reactions described in this section reflect exposure to MYLOTARG 3 mg/m2 on Days 1, 4 and 7 as
monotherapy in 57 patients with relapsed AML treated on MyloFrance-1. All 57 (100%) patients received the 3
planned doses of MYLOTARG. During the treatment period, Grade 3 treatment-emergent adverse events (TEAEs)
that occurred in greater than 1% patients included sepsis (32%), fever (16%), rash (11%), pneumonia (7%),
bleeding (7%), mucositis (4%), pain (4%), diarrhea (2%), headaches (2%), tachycardia (2%), and lung edema
(2%). No Grade 4 toxicity was observed. All grade TEAEs that occurred in greater than 15% of patients included
fever (79%), infection (42%), increased AST (40%), bleeding (23%), nausea and vomiting (21%), constipation
(21%), mucositis (21%), headache (19%), increased ALT (16%), and rash (16%). No infectious deaths occurred.
Grade 1 or 2 hyperbilirubinemia developed in 4 (7%) patients. No episodes of VOD occurred. Seven patients
received HSCT after MYLOTARG treatment. Three patients received an allogeneic BMT and 4 patients were treated
with autologous BMT. No patients developed VOD following HSCT.
Postmarketing Experience: The following adverse drug reactions have been identified during postapproval use of MYLOTARG. Because these reactions are reported voluntarily from a population of
uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship
to drug exposure. Gastrointestinal Disorders: Neutropenic colitis*; Infections and Infestations: fungal lung
infections including Pulmonary mycosis and Pneumocystis jirovecii pneumonia*; and bacterial infections
including Stenotrophomonas infection; Renal and Urinary Disorders: Hemorrhagic cystitis1; Respiratory, Thoracic
and Mediastinal Disorders: Interstitial pneumonia.1 (*including fatal events.)
Immunogenicity: As with all therapeutic proteins, there is potential for immunogenicity. Immunogenicity of
MYLOTARG was not studied in clinical trials using the recommended dose regimens.
USE IN SPECIFIC POPULATIONS
Pregnancy: Risk Summary: Based on its mechanism of action and findings from animal studies, MYLOTARG
can cause embryo-fetal harm when administered to a pregnant woman. There are no available data on
MYLOTARG use in pregnant women to inform a drug-associated risk of major birth defects and miscarriage.
In rat embryo-fetal development studies, gemtuzumab ozogamicin caused embryo-fetal toxicity at maternal
systemic exposures that were greater than or equal to 0.4 times the exposure in patients at the maximum
recommended dose, based on AUC. If MYLOTARG is used during pregnancy, or if the patient becomes pregnant
while taking MYLOTARG, advise the patient of the potential risk to a fetus. Adverse outcomes in pregnancy occur
regardless of the health of the mother or the use of medications. The estimated background risk of major birth
defects and miscarriage for the indicated population is unknown. In the U.S. general population, the estimated
background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2-4% and 15-20%,
respectively. Data: Animal Data: In an embryo-fetal development study in rats, pregnant animals received daily
intravenous doses up to 1.2 mg/m2/day gemtuzumab ozogamicin during the period of organogenesis. Embryofetal toxicities including fetal growth retardation as evidenced by decreased live fetal weights, incidence of fetal
wavy ribs and delayed skeletal ossification were observed at greater than or equal to 0.15 mg/m2/day. Increased
embryo-fetal lethality and fetal morphological anomalies (digital malformations, absence of the aortic arch,
anomalies in the long bones in the forelimbs, misshapen scapula, absence of a vertebral centrum, and fused
sternebrae) were observed at greater than or equal to 0.36 mg/m2/day. All doses with embryo-fetal effects

were observed in the presence of maternal toxicity that included decreases in gestational body weight gain,
food consumption, and gravid uterine weight. The lowest dose at which embryo-fetal effects were observed
in rats (0.15 mg/m2/day) was 0.4 times the exposure in patients at the maximum recommended human dose,
based on AUC.
Lactation: Risk Summary: There are no data on the presence of gemtuzumab ozogamicin or its metabolites in
human milk, the effects on the breastfed infant, or the effects on milk production. Because of the potential for
adverse reactions in breastfed infants, women should not breastfeed during treatment with MYLOTARG and for
at least 1 month after the final dose.
Females and Males of Reproductive Potential: Pregnancy Testing: Based on animal studies, MYLOTARG can cause
fetal harm when administered to a pregnant woman. Verify the pregnancy status of females of reproductive
potential prior to initiating MYLOTARG. Contraception: Females: Advise females of reproductive potential to
avoid becoming pregnant while receiving MYLOTARG. Advise females of reproductive potential to use effective
contraception during treatment with MYLOTARG and for at least 6 months after the last dose. Males: Advise males
with female partners of reproductive potential to use effective contraception during treatment with MYLOTARG and
for at least 3 months after the last dose. Infertility: Females: Based on findings in animals, MYLOTARG may impair
fertility in females of reproductive potential. Males: Based on findings in animals, MYLOTARG may impair fertility in
males of reproductive potential.
Pediatric Use: The safety and efficacy of MYLOTARG in combination with daunorubicin and cytarabine have
not been established in the pediatric patients with newly-diagnosed de novo AML. The safety and efficacy of
MYLOTARG as a single agent in the pediatric patients with relapsed or refractory AML is supported by a singlearm trial in 29 patients in the following age groups: 1 patient 1 month to less than 2 years old, 13 patients 2 years
to less than 12 years old, and 15 patients 12 years to 18 years old. A literature review included an additional 96
patients with ages ranging from 0.2 to 21 years. No differences in efficacy and safety were observed by age.
Geriatric Use: Use of MYLOTARG in combination with daunorubicin and cytarabine in newly-diagnosed adult
patients with de novo AML is supported by a randomized, controlled trial that included 50 patients greater
than or equal to 65 years old. No overall differences in safety or effectiveness were observed between these
subjects and younger subjects. Use of MYLOTARG monotherapy in newly-diagnosed adult patients with AML
is supported by a randomized controlled trial with 118 patients treated with MYLOTARG. All patients were over
the age of 60 years and 65% of patients were above 75 years. No overall differences in effectiveness were
observed by age. Use of MYLOTARG as single-agent treatment of relapsed or refractory AML is supported by a
single-arm trial that included 27 patients 65 years or older. No overall differences in effectiveness were observed
between these patients and younger patients. Elderly patients experienced a higher rate of fever and severe
or greater infections.
PATIENT COUNSELING INFORMATION
Hepatotoxicity, Including Veno-occlusive Liver Disease (VOD): Inform patients that liver problems,
including severe, life-threatening, or fatal VOD may develop during MYLOTARG treatment. Prior to receiving
MYLOTARG, inform patients who previously received, or will receive an HSCT that they may be at increased
risk for developing VOD. Inform patients that the risk of developing VOD after an allogeneic HSCT is increased
after receiving treatment with MYLOTARG. Inform patients that signs or symptoms of liver toxicity, including
rapid weight gain, right upper quadrant pain and tenderness, hepatomegaly, and ascites should be
monitored regularly during treatment, but these symptoms may not identify all patients at risk or prevent
the complications of liver toxicity. Inform patients that liver problems may require dosing interruption
or permanent discontinuation of MYLOTARG. Hemorrhage: Inform patients that decreased platelet
counts, which may be life-threatening, may develop during MYLOTARG treatment and that complications
associated with decreased platelet counts may include bleeding/hemorrhage events, which may
be life-threatening or fatal. Inform patients to report signs and symptoms of bleeding/hemorrhage
during treatment with MYLOTARG. Inform patients that severe bleeding/hemorrhage may require dosing
interruption or permanent discontinuation of MYLOTARG. Infusion Related Reactions: Advise patients to
contact their health care provider if they experience signs and symptoms of infusion related reactions,
including symptoms such as fever, chills, rash, or breathing problems. Pregnancy and Breastfeeding: Advise
men and women of reproductive potential to use effective contraception during MYLOTARG treatment and for
at least 3 and 6 months, respectively, after the last dose. Advise women of childbearing potential to avoid
becoming pregnant while receiving MYLOTARG. Advise women to contact their healthcare provider if they
become pregnant, or if pregnancy is suspected, during treatment with MYLOTARG. Inform the patient of the
potential hazard to the fetus. Advise women against breastfeeding while receiving MYLOTARG and for 1 month
after the last dose.
Rx only
This brief summary is based on MYLOTARG Prescribing Information LAB-0868-1.0, revised September 2017, which
can be found at MylotargHCP.com.

Printed in USA/September 2017

T:10"

Liver
Fatigue
Infection
Cardiac
Bleeding
Febrile neutropenia
Metabolic
Renal

Best Supportive Care
n=114

perimental tools
to study cancer
evolution
and
seeks to apply
this
knowledge
to design the next
generation
of
precision medicine to overcome
cancer evolution. He has led comprehensive studies of genetic and
epigenetic aspects of cancer evolution and received prestigious
awards including the Burroughs
Wellcome Fund Career Award for
Medical Scientists, the Kimmel
Scholar's Award, a K01 from the

National Institutes of Health Big
Data to Knowledge initiative, and
the Stand Up to Cancer Innovative
Research Award.
Emily Mace, PhD
Dr. Mace is an assistant professor of pediatrics at Baylor College
of Medicine, where she studies
the mechanisms of human innate
immune cell development. She received her PhD from the University of British Columbia, where she
worked at the Terry Fox Laboratory under the supervision of Dr.
Fumio Takei. Her graduate thesis
used in vitro differentiation of talindeficient natural killer (NK) cells
to define the integrin-dependent
pathway of actin reorganization in
NK cells. She then completed postdoctoral training
at the Children's
Hospital of Philadelphia and subsequently Baylor
College of Medicine in Houston.
Dr. Mace's postdoctoral research
focused on understanding human NK cell function,
including through the application
of high- and super-resolution imaging techniques to the immunological synapse. Her independent
research program applies multidimensional quantitative imaging to
determining the cell-cell contacts
that drive human NK cell differentiation. She additionally seeks to
define requirements for human NK
cell development through the study
of rare patients with primary immune deficiencies that selectively
affect NK cell maturation, including GATA2 deficiency and biallelic
IRF8 deficiency.
Jeffrey Magee, MD, PhD
Dr. Magee is an assistant professor of pediatrics at Washington
University School of Medicine,
specializing in the care of children
with leukemia. He
completed undergraduate studies
at the University
of Wisconsin and
earned his MD/
PhD at Washington
University.
He trained as a
pediatric
oncology fellow at the
University of Michigan and as a
postdoctoral fellow in Dr. Sean
Morrison's laboratory at University
of Texas-Southwestern. He joined
the Washington University faculty
in 2013. Dr. Magee is interested in
understanding why children get
leukemia and how their leukemias
»» ASH SCHOLARS Page B-30

Table of Contents for the Digital Edition of ASH News Daily 2017 - Issue 3