ASH Clinical News March 2016 | Page 44

Calendar
International Bone Marrow Failure
Disease Scientific Symposium

March 17 – 18, 2016
Rockville, MD
The Aplastic Anemia & MDS International Foundation
is hosting an intensive, two-day conference convening
international experts at the forefront of research and
treatment of bone marrow failure disease.

National Comprehensive Cancer
Network Annual Conference

March 31 – April 2, 2016
Hollywood, FL
The theme of this year’s NCCN Annual Conference is
“Advancing the Standard of Cancer Care.” Attendees
will discuss the latest cancer therapies, quality initiatives, and selected NCCN Clinical Practice Guidelines in
Oncology.

American Association of Cancer
Research Annual Meeting

April 16 – 20, 2016
New Orleans, LA
The AACR Annual Meeting will highlight the latest discoveries in every area of cancer research, from molecular
biology to clinical studies, epidemiology, prevention, and
survivorship.

International Society of Hematology
36th World Congress

April 18 – 21, 2016
Glasgow, Scotland, UK
The 36th World Congress, hosted by the British Society
of Hematology, gathers international members of the
hematology community to network and discuss the
changing clinical and laboratory practice landscape, as
well as report on advances in the field.

Highlights of ASH®

BRIEF SUMMARY OF PRESCRIBING INFORMATION FOR
GRANIX® (tbo-filgrastim) injection, for subcutaneous use
SEE PACKAGE INSERT FOR FULL PRESCRIBING INFORMATION
1
INDICATIONS AND USAGE
GRANIX is indicated to reduce the duration of severe neutropenia in patients with nonmyeloid malignancies receiving myelosuppressive anti-cancer drugs associated with a
clinically significant incidence of febrile neutropenia.
4
CONTRAINDICATIONS
None.
5
WARNINGS AND PRECAUTIONS
5.1
Splenic Rupture
Splenic rupture, including fatal cases, can occur following administration of human granulocyte colony-stimulating factors. In patients who report upper abdominal or shoulder
pain after receiving GRANIX, discontinue GRANIX and evaluate for an enlarged spleen or
splenic rupture.
5.2
Acute Respiratory Distress Syndrome (ARDS)
Acute respiratory distress syndrome (ARDS) can occur in patients receiving human granulocyte colony-stimulating factors. Evaluate patients who develop fever and lung infiltrates
or respiratory distress after receiving GRANIX, for ARDS. Discontinue GRANIX in patients
with ARDS.
5.3
Allergic Reactions
Serious allergic reactions including anaphylaxis can occur in patients receiving human
granulocyte colony-stimulating factors. Reactions can occur on initial exposure. The
administration of antihistamines‚ steroids‚ bronchodilators‚ and/or epinephrine may
reduce the severity of the reactions. Permanently discontinue GRANIX in patients with
serious allergic reactions. Do not administer GRANIX to patients with a history of serious
allergic reactions to filgrastim or pegfilgrastim.
5.4
Use in Patients with Sickle Cell Disease
Severe and sometimes fatal sickle cell crises can occur in patients with sickle cell disease
receiving human granulocyte colony-stimulating factors. Consider the potential risks and benefits prior to the administration of human granulocyte colony-stimulating factors in patients
with sickle cell disease. Discontinue GRANIX in patients undergoing a sickle cell crisis.
5.5
Capillary Leak Syndrome
Capillary leak syndrome (CLS) can occur in patients receiving human granulocyte colonystimulating factors and is characterized by hypotension, hypoalbuminemia, edema and
hemoconcentration. Episodes vary in frequency, severity and may be life-threatening if
treatment is delayed. Patients who develop symptoms of capillary leak syndrome should
be closely monitored and receive standard symptomatic treatment, which may include a
need for intensive care.
5.6
Potential for Tumor Growth Stimulatory Effects on Malignant Cells
The granulocyte colony-stimulating factor (G-CSF) receptor through which GRANIX acts
has been found on tumor cell lines. The possibility that GRANIX acts as a growth factor for
any tumor type, including myeloid malignancies and myelodysplasia, diseases for which
GRANIX is not approved, cannot be excluded.
6
ADVERSE REACTIONS
The following potential serious adverse reactions are discussed in greater detail in other
sections of the labeling:
• Splenic Rupture [see Warnings and Precautions (5.1)]
• Acute Respiratory Distress Syndrome [see Warnings and Precautions (5.2)]
• Serious Allergic Reactions [see Warnings and Precautions (5.3)]
• Use in Patients with Sickle Cell Disease [see Warnings and Precautions (5.4)]
• Capillary Leak Syndrome [see Warnings and Precautions (5.5)]
• Potential for Tumor Growth Stimulatory Effects on Malignant Cells [see Warnings and
Precautions (5.6)]
The most common treatment-emergent adverse reaction that occurred at an incidence of
at least 1% or greater in patients treated with GRANIX at the recommended dose and was
numerically two times more frequent than in the placebo group was bone pain.
6.1
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 clinical practice .
GRANIX clinical trials safety data are based upon the results of three randomized clinical
trials in patients receiving myeloablative chemotherapy for breast cancer (N=348), lung
cancer (N=240) and non-Hodgkin’s lymphoma (N=92). In the breast cancer study, 99% of
patients were female, the median age was 50 years, and 86% of patients were Caucasian.
In the lung cancer study, 80% of patients were male, the median age was 58 years, and
95% of patients were Caucasian. In the non-Hodgkin’s lymphoma study, 52% of patients
were male, the median age was 55 years, and 88% of patients were Caucasian. In all three
studies a placebo (Cycle 1 of the breast cancer study only) or a non-US-approved filgrastim product were used as controls. Both GRANIX and the non-US-approved filgrastim
product were administered at 5 mcg/kg subcutaneously once daily beginning one day
after chemotherapy for at least five days and continued to a maximum of 14 days or until
an ANC of ≥10,000 x 106/L after nadir was reached.

Bone pain was the most frequent treatment-emergent adverse reaction that occurred in at
least 1% or greater in patients treated with GRANIX at the recommended dose and was
numerically two times more frequent than in the placebo group. The overall incidence of
bone pain in Cycle 1 of treatment was 3.4% (3.4% GRANIX, 1.4% placebo, 7.5% non-USapproved filgrastim product).
Leukocytosis
In clinical studies, leukocytosis (WBC counts > 100,000 x 106/L) was observed in less than
1% patients with non-myeloid malignancies receiving GRANIX. No complications attributable to leukocytosis were reported in clinical studies.
Additional Adverse Reactions
Other adverse reactions known to occur following administration of human granulocyte
colony-stimulating factors include myalgia, headache, vomiting, Sweet’s syndrome (acute
febrile neutrophilic dermatosis), cutaneous vasculitis and thrombocytopenia.
6.2
Immunogenicity
As with all therapeutic proteins, there is a potential for immunogenicity. The incidence of
antibody development in patients receiving GRANIX has not been adequately determined.
7
DRUG INTERACTIONS
No formal drug interaction studies between GRANIX and other drugs have been performed.
Drugs which may potentiate the release of neutrophils‚ such as lithium‚ should be used
with caution.
Increased hematopoietic activity of the bone marrow in response to growth factor therapy
has been associated with transient positive bone imaging changes. This should be considered when interpreting bone-imaging results.
8
USE IN SPECIFIC POPULATIONS
8.1
Pregnancy
Pregnancy Category C
Risk Summary
There are no adequate and well-controlled studies of GRANIX in pregnant women. In
animal reproduction studies, treatment of pregnant rabbits with tbo-filgrastim resulted in
increased spontaneous abortion and fetal malformations at systemic exposures substantially higher than the human exposure. GRANIX should be used during pregnancy only if
the potential benefit justifies the potential risk to the fetus.
Animal Data
In an embryofetal developmental study, pregnant rabbits were administered subcutaneous
doses of tbo-filgrastim during the period of organogenesis at 1, 10 and 100 mcg/kg/day.
Increased abortions were evident in rabbits treated with tbo-filgrastim at 100 mcg/kg/day.
This dose was maternally toxic as demonstrated by reduced body weight. Other embryofetal findings at this dose level consisted of post-implantation loss‚ decrease in mean
live litter size and fetal weight, and fetal malformations such as malformed hindlimbs and
cleft palate. The dose of 100 mcg/kg/day corresponds to a systemic exposure (AUC) of
approximately 50-90 times the exposures observed in patients treated with the clinical
tbo-filgrastim dose of 5 mcg/kg/day.
8.3
Nursing Mothers
It is not known whether tbo-filgrastim is secreted in human milk. Because many drugs
are excreted in human milk, caution should be exercised when GRANIX is administered to
a nursing woman. Other recombinant G-CSF products are poorly secreted in breast milk
and G-CSF is not orally absorbed by neonates.
8.4
Pediatric Use
The safety and effectiveness of GRANIX in pediatric patients have not been established.
8.5
Geriatric Use
Among 677 cancer patients enrolled in clinical trials of GRANIX, a total of 111 patients
were 65 years of age and older. No overall differences in safety or effectiveness were
observed between patients age 65 and older and younger patients.
8.6
Renal Impairment
The safety and efficacy of GRANIX have not been studied in patients with moderate or
severe renal impairment. No dose adjustment is recommended for patients with mild
renal impairment.
8.7
Hepatic Impairment
The safety and efficacy of GRANIX have not been studied in patients with hepatic impairment.
10
OVERDOSAGE
No case of overdose has been reported.
©2014 Cephalon, Inc., a wholly-owned subsidiary of Teva Pharmaceutical Industries Ltd.
All rights reserved.
GRANIX is a registered trademark of Teva Pharmaceutical Industries Ltd.
Manufactured by:
Distributed by:
Sicor Biotech UAB
Teva Pharmaceuticals USA, Inc.
Vilnius, Lithuania
North Wales, PA 19454
U.S. License No. 1803
Product of Israel
GRX-40580 January 2015
This brief summary is based on TBO-004 GRANIX full Prescribing Information.

Get a synopsis of the top hematology research presented
at the 2015 ASH Annual Meeting and learn how it can
help improve your patient management and care
strategies. This is an opportunity to evaluate your
diagnostic techniques and therapeutic approaches
and discuss with leading hematology experts and
colleagues how new research and clinical updates
can be translated into patient care strategies.
There is one remaining meeting this year:
April 29 – 30, 2016
Porto Alegre, Brazil
*Please note the change in location from what
was previously published in past issues.

Oncology Nursing Society
Annual Congress

April 28, 2016 – May 1, 2016
San Antonio, TX
This year’s Annual Congress will feature the latest
developments in oncology nursing and patient
care, as well as networking opportunities for the
more than 3,000 attendees.

European Hematology A ssociation
Annual Congress
June 9 – 12, 2016
Copenhagen, Denmark
The 21st Annual Congress will provide a forum
for sharing clinical and translational research
in hematologic disorders and disseminating
evidence-based knowledge.

ASH Meeting on Lymphoma Biology

June 18 – 21, 2016
Colorado Springs, CO
The ASH Meeting on Lymphoma Biology brings
together experts from around the world to discuss
the latest breakthroughs in basic and translational
lymphoma research, address current challenges in
the field, and exchange ideas on how to move the
field forward.

Washington, DC, skyline

ASH Workshop on Genome Editing

July 14 – 15, 2016
Washington, DC
The ASH Workshop on Genome Editing provides a
forum that focuses specifically on the mechanistic
aspects and possible clinical applications of this
technology to blood disorders, as well as a platform for the exchange of ideas between academic
researchers, industry scientists, and regulators
involved in the clinical application of genome
editing technology.

March 2016