ASH News Daily 2017 - Issue 3 - B-38

ASH News Daily

Page B-38

Monday, December 11, 2017

VTP

«« From Page B-18

her to summer farmer's markets,
breweries around Milwaukee, a
baseball game, and even apple picking this fall," adding that Dr. Saldarriaga embraced not only her time
spent on professional/academic
training, but the social and cultural
immersion that took place as well.
It is worth mentioning that Dr.
Thakar volunteered with ASH's
Health Volunteers Overseas (HVO)
program as well and spent two weeks
in Lima during 2013, where she met
Dr. Saldarriaga and her numerous

colleagues. Having traveled to Peru
definitely benefited her perspective,
Dr. Thakar feels. "To see their surroundings, learn of their resources,
and meet their patients provided me
a unique insight." With that insight,
Dr. Thakar was able to identify and
fine-tune specific skills for Dr. Saldarriaga to learn before returning home
from the VTP experience.
In terms of challenges, Dr. Thakar
was pleased to cite the relative ease
of the VTP process - from budgeting for a stipend, to short-term housing for Dr. Saldarriaga. The "observer" status of the participants (i.e., no
direct patient care allowed), was one

area she imagined might pose a challenge for a trained physician such as
Dr. Saldarriaga; however, Dr. Thakar said that it was no trouble after
all. She stressed the value of the host
institution as a community of learning, with the entire team involved in
welcoming and embracing the international visitor. "She has learned a
considerable amount and is truly a
part of our team."
For those who might consider
mentoring a VTP awardee, Dr. Thakar cannot say enough about how
rewarding the experience was for
her. "For anyone who has an interest and passion for global health but

CALQUENCE® (acalabrutinib) capsules, for oral use
Initial U.S. Approval: 2017
Brief Summary of Prescribing Information. For complete prescribing information consult
official package insert.
INDICATIONS AND USAGE
CALQUENCE is indicated for the treatment of adult patients with mantle cell lymphoma (MCL)
who have received at least one prior therapy.
This indication is approved under accelerated approval based on overall response rate [see
Clinical Studies (14) in the full Prescribing Information]. Continued approval for this indication
may be contingent upon verification and description of clinical benefit in confirmatory trials.
DOSAGE AND ADMINISTRATION
Recommended Dosage
The recommended dose of CALQUENCE is 100 mg taken orally approximately every twelve
hours until disease progression or unacceptable toxicity.
Advise patients to swallow capsule whole with water. Advise patients not to open, break or
chew the capsules. CALQUENCE may be taken with or without food. If a dose of CALQUENCE
is missed by more than 3 hours, it should be skipped and the next dose should be taken at
its regularly scheduled time. Extra capsules of CALQUENCE should not be taken to make up
for a missed dose.
Dose Modifications
Adverse Reactions
Recommended dose modifications of CALQUENCE for Grade 3 or greater adverse reactions
are provided in Table 1.
Table 1: Recommended Dose Modifications for Adverse Reactions
Adverse Reaction Dose Modification
Occurrence
(Starting dose = 100 mg twice daily)
Grade 3 or greater
Interrupt CALQUENCE.
non-hematologic toxicities,
First and Second Once toxicity has resolved to Grade 1 or
baseline level, CALQUENCE therapy may
Grade 3 thrombocytopenia
be resumed at 100 mg twice daily.
with bleeding,
Grade 4
Interrupt CALQUENCE.
thrombocytopenia
Once toxicity has resolved to Grade 1 or
Third
or
baseline level, CALQUENCE therapy may
be resumed at 100 mg daily.
Grade 4 neutropenia
lasting longer than
Fourth
Discontinue CALQUENCE.
7 days
Event

Adverse reactions graded by the National Cancer Institute Common Terminology Criteria for Adverse
Events (NCI CTCAE) version 4.03.

Dose Modifications for Use with CYP3A Inhibitors or Inducers
Recommended dose modifications are described below [see Drug Interactions (7) in the full
Prescribing Information].
CYP3A

Inhibition

Induction

Co-administered Drug

Recommended CALQUENCE use
Avoid concomitant use.
If these inhibitors will be used short-term
Strong CYP3A inhibitor
(such as anti-infectives for up to seven days),
interrupt CALQUENCE.
Moderate CYP3A inhibitor 100 mg once daily.
Avoid concomitant use.
Strong CYP3A inducer
If these inducers cannot be avoided, increase
CALQUENCE dose to 200 mg twice daily.

Concomitant Use with Gastric Acid Reducing Agents
Proton Pump Inhibitors: Avoid concomitant use [see Drug Interactions (7) in the full
Prescribing Information].
H2-Receptor Antagonists: Take CALQUENCE 2 hours before taking a H2-receptor antagonist
[see Drug Interactions (7) in the full Prescribing Information].
Antacids: Separate dosing by at least 2 hours [see Drug Interactions (7) in the full
Prescribing Information].
CONTRAINDICATIONS
None.
WARNINGS AND PRECAUTIONS
Hemorrhage
Serious hemorrhagic events, including fatal events, have occurred in the combined safety
database of 612 patients with hematologic malignancies treated with CALQUENCE
monotherapy. Grade 3 or higher bleeding events, including gastrointestinal, intracranial,
and epistaxis have been reported in 2% of patients. Overall, bleeding events including
bruising and petechiae of any grade occurred in approximately 50% of patients with
hematological malignancies.
The mechanism for the bleeding events is not well understood. CALQUENCE may further
increase the risk of hemorrhage in patients receiving antiplatelet or anticoagulant therapies
and patients should be monitored for signs of bleeding. Consider the benefit-risk of
withholding CALQUENCE for 3-7 days pre- and post-surgery depending upon the type of
surgery and the risk of bleeding.
Infection
Serious infections (bacterial, viral or fungal), including fatal events and opportunistic
infections have occurred in the combined safety database of 612 patients with hematologic
malignancies treated with CALQUENCE monotherapy. Consider prophylaxis in patients who
are at increased risk for opportunistic infections.

US-14432_US-14202 Calquence ASH News Daily 2017.indd 3

doesn't have the time or ability to
visit international sites, this is one
way to 'give back,' even in our subspecialized fields."
She also stresses that the giving
can be a two-way street. "Dr. Saldarriaga gave our hematology/oncology BMT division a talk at the end
of her rotation discussing aspects
of health care in Peru, what she has
learned, and what she will be bringing home with her. The education
goes both ways!"
To get involved and to learn more
about this and other ASH global
initiatives, visit www.hematology.org/
global.

Grade 3 or higher infections occurred in 18% of these patients. The most frequently reported
Grade 3 or 4 infection was pneumonia. Infections due to hepatitis B virus (HBV) reactivation
and progressive multifocal leukoencephalopathy (PML) have occurred. Monitor patients for
signs and symptoms of infection and treat as medically appropriate.
Cytopenias
In the combined safety database of 612 patients with hematologic malignancies, patients
treated with CALQUENCE monotherapy experienced Grade 3 or 4 cytopenias, including
neutropenia (23%), anemia (11%) and thrombocytopenia (8%) based on laboratory
measurements. In the CALQUENCE clinical Trial LY-004, patients' complete blood counts
were assessed monthly during treatment.
Second Primary Malignancies
Second primary malignancies, including non-skin carcinomas, have occurred in 11% of
patients with hematologic malignancies treated with CALQUENCE monotherapy in the
combined safety database of 612 patients. The most frequent second primary malignancy
was skin cancer, reported in 7% of patients. Advise protection from sun exposure.
Atrial Fibrillation and Flutter
In the combined safety database of 612 patients with hematologic malignancies treated with
CALQUENCE monotherapy, atrial fibrillation and atrial flutter of any grade occurred in 3%
of patients, and Grade 3 in 1% of patients. Monitor for atrial fibrillation and atrial flutter and
manage as appropriate.
ADVERSE REACTIONS
The following adverse reactions are discussed in greater detail in other sections of
the labeling:
* Hemorrhage [see Warnings and Precautions (5.1) in the full Prescribing Information]
* Infection [see Warnings and Precautions (5.2) in the full Prescribing Information]
* Cytopenias [see Warnings and Precautions (5.3) in the full Prescribing Information]
* Second Primary Malignancies [see Warnings and Precautions (5.4) in the full Prescribing
Information]
* Atrial Fibrillation and Flutter [see Warnings and Precautions (5.5) in the full Prescribing
Information]
Clinical Trials Experience
As 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.
The safety data described in this section reflect exposure to CALQUENCE (100 mg twice
daily) in 124 patients with previously treated MCL in Trial LY-004 [see Clinical Studies (14)
in the full Prescribing Information]. The median duration of treatment with CALQUENCE
was 16.6 (range 0.1 to 26.6) months. A total of 91 (73.4%) patients were treated with
CALQUENCE for ≥ 6 months and 74 (59.7%) patients were treated for ≥ 1 year.
The most common adverse reactions (≥ 20%) of any grade were anemia, thrombocytopenia,
headache, neutropenia, diarrhea, fatigue, myalgia, and bruising. Grade 1 severity for
the non-hematologic, most common events were as follows: headache (25%), diarrhea
(16%), fatigue (20%), myalgia (15%), and bruising (19%). The most common Grade ≥ 3
non-hematological adverse reaction (reported in at least 2% of patients) was diarrhea.
Dose reductions or discontinuation due to any adverse reaction were reported in 1.6% and
6.5% of patients, respectively.
Tables 2 and 3 present the frequency category of adverse reactions observed in patients with
MCL treated with CALQUENCE.
Table 2: Non-Hematologic Adverse Reactions* in ≥ 5% (All Grades) of Patients with MCL
in Trial LY-004
Body System
Adverse Reactions

CALQUENCE 100 mg twice daily
N=124
All Grades (%)
Grade ≥ 3 (%)

Nervous system disorders
Headache
39
Gastrointestinal disorders
Diarrhea
31
Nausea
19
Abdominal pain
15
Constipation
15
Vomiting
13
General Disorders
Fatigue
28
Musculoskeletal and connective tissue disorders
Myalgia
21
Skin & subcutaneous tissue disorders
Bruising†
21
Rash†
18
Vascular disorders
8
Hemorrhage/Hematoma†
Respiratory, thoracic & mediastinal disorders
Epistaxis
6

1.6
3.2
0.8
1.6
1.6
0.8
0.8
0.8
0.8
-

* Per National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) version 4.03.
†
Bruising: Includes all preferred terms (PTs) containing 'bruise,' 'contusion,' 'petechiae,' or 'ecchymosis'
Rash: Includes all PTs containing 'rash'
Hemorrhage/hematoma: Includes all PTs containing 'hemorrhage' or 'hematoma'

11/10/17 3:00 PM

http://www.hematology.org/global http://www.hematology.org/global

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