ASH News Daily 2017 - Issue 2 - B-38

ASH | Academy

free ASH Teaching Cases!
®

ASH News Daily

Page B-38
®

Visit www.ashacademy.org to accessSunday,
free ASH Teaching
Cases,
December
a fun and interactive educational resource for instructors, students,
and anyone who wishes to test their patient-care knowledge.

10, 2017

* test standard approaches to classic hematology problems

Test your knowledge with
free ASH Teaching Cases!

* walk through simulated steps involved in diagnosing a patient
* review teaching points with bibliography and links to references

Works
g
on mob reat
devicesile
!

Visit www.ashacademy.org to access free ASH Teaching Cases,
a fun and interactive educational resource for instructors, students,
and anyone who wishes to test their patient-care knowledge.
* test standard approaches to classic hematology problems
* walk through simulated steps involved in diagnosing a patient
* review teaching points with bibliography and links to references

Works
g
on mob reat
devicesile
!

American Society of Hematology

Grade 3 or higher
infections
occurred
in 18% of these patients. The most frequently reported
CALQUENCE® (acalabrutinib) capsules, for oral use
Helping hematologists
conquer
blood diseases
worldwide
Grade 3 or 4 infection was pneumonia. Infections due to hepatitis B virus (HBV) reactivation
Initial U.S. Approval: 2017
and progressive multifocal leukoencephalopathy (PML) have occurred. Monitor patients for
Brief Summary of Prescribing Information. For complete prescribing information consult
signs and symptoms of infection and treat as medically appropriate.
ASH AND 2017 Teaching Cases JUNIOR 7x10 ad.indd 1
11/3/17 5:23 PM
official package insert.
Cytopenias
INDICATIONS AND USAGE
In the combined safety database of 612 patients with hematologic malignancies, patients
CALQUENCE is indicated for the treatment of adult patients with mantle cell lymphoma (MCL)
treated with CALQUENCE monotherapy experienced Grade 3 or 4 cytopenias, including
who have received at least one prior therapy.
neutropenia (23%), anemia (11%) and thrombocytopenia (8%) based on laboratory
This indication is approved under accelerated approval based on overall response rate [see
measurements. In the CALQUENCE clinical Trial LY-004, patients' complete blood counts
Clinical Studies (14) in the full Prescribing Information]. Continued approval for this indication
were assessed monthly during treatment.
may be contingent upon verification and description of clinical benefit in confirmatory trials.
Second Primary Malignancies
DOSAGE AND ADMINISTRATION
Second primary malignancies, including non-skin carcinomas, have occurred in 11% of
patients with hematologic malignancies treated with CALQUENCE monotherapy in the
Recommended Dosage
combined safety database of 612 patients. The most frequent second primary malignancy
The recommended dose of CALQUENCE is 100 mg taken orally approximately every twelve
was skin cancer, reported in 7% of patients. Advise protection from sun exposure.
hours until disease progression or unacceptable toxicity.
Advise patients to swallow capsule whole with water. Advise patients not to open, break or
Atrial Fibrillation and Flutter
chew the capsules. CALQUENCE may be taken with or without food. If a dose of CALQUENCE
In the combined safety database of 612 patients with hematologic malignancies treated with
is missed by more than 3 hours, it should be skipped and the next dose should be taken at
CALQUENCE monotherapy, atrial fibrillation and atrial flutter of any grade occurred in 3%
its regularly scheduled time. Extra capsules of CALQUENCE should not be taken to make up
of patients, and Grade 3 in 1% of patients. Monitor for atrial fibrillation and atrial flutter and
for a missed dose.
manage as appropriate.
Dose Modifications
ADVERSE REACTIONS
Adverse Reactions
The following adverse reactions are discussed in greater detail in other sections of
Recommended dose modifications of CALQUENCE for Grade 3 or greater adverse reactions
the labeling:
are provided in Table 1.
* Hemorrhage [see Warnings and Precautions (5.1) in the full Prescribing Information]
Table 1: Recommended Dose Modifications for Adverse Reactions
* Infection [see Warnings and Precautions (5.2) in the full Prescribing Information]
* Cytopenias [see Warnings and Precautions (5.3) in the full Prescribing Information]
Adverse
Reaction
Dose
Modification
Event
* Second Primary Malignancies [see Warnings and Precautions (5.4) in the full Prescribing
Occurrence
(Starting dose = 100 mg twice daily)
Information]
Grade 3 or greater
Interrupt CALQUENCE.
* Atrial Fibrillation and Flutter [see Warnings and Precautions (5.5) in the full Prescribing
non-hematologic toxicities,
Information]
First and Second Once toxicity has resolved to Grade 1 or
baseline level, CALQUENCE therapy may
Grade 3 thrombocytopenia
Clinical Trials Experience
be resumed at 100 mg twice daily.
with bleeding,
As clinical trials are conducted under widely varying conditions, adverse reaction rates
Grade 4
Interrupt CALQUENCE.
observed in the clinical trials of a drug cannot be directly compared to rates in the clinical
thrombocytopenia
Once
toxicity
has
resolved
to
Grade
1
or
trials of another drug and may not reflect the rates observed in practice.
Third
or
baseline level, CALQUENCE therapy may
The safety data described in this section reflect exposure to CALQUENCE (100 mg twice
be resumed at 100 mg daily.
Grade 4 neutropenia
daily) in 124 patients with previously treated MCL in Trial LY-004 [see Clinical Studies (14)
lasting longer than
in the full Prescribing Information]. The median duration of treatment with CALQUENCE
Fourth
Discontinue CALQUENCE.
7 days
was 16.6 (range 0.1 to 26.6) months. A total of 91 (73.4%) patients were treated with
Helping hematologists conquer blood diseases worldwide
Adverse reactions graded by the National Cancer Institute Common Terminology Criteria for Adverse
CALQUENCE for ≥ 6 months and 74 (59.7%) patients were treated for ≥ 1 year.
Events (NCI CTCAE) version 4.03.
The most common adverse reactions (≥ 20%) of any grade were anemia, thrombocytopenia,
Dose Modifications for Use with CYP3A Inhibitors or Inducers
headache, neutropenia, diarrhea, fatigue, myalgia, and bruising. Grade 1 severity for
the non-hematologic, most common events were as follows: headache (25%), diarrhea
Recommended dose modifications are described below [see Drug Interactions (7) in the full
ASH AND 2017 Teaching Cases JUNIOR 7x10 ad.indd 1
11/3/17 5:23 PM
(16%), fatigue (20%), myalgia (15%), and bruising (19%). The most common Grade ≥ 3
Prescribing Information].
non-hematological adverse reaction (reported in at least 2% of patients) was diarrhea.
CYP3A
Co-administered Drug
Recommended CALQUENCE use
Dose reductions or discontinuation due to any adverse reaction were reported in 1.6% and
Avoid concomitant use.
6.5% of patients, respectively.
If these inhibitors will be used short-term
Tables 2 and 3 present the frequency category of adverse reactions observed in patients with
Strong CYP3A inhibitor
(such as anti-infectives for up to seven days),
Inhibition
MCL treated with CALQUENCE.
interrupt CALQUENCE.
Table 2: Non-Hematologic Adverse Reactions* in ≥ 5% (All Grades) of Patients with MCL
Moderate CYP3A inhibitor 100 mg once daily.
in Trial LY-004
Avoid concomitant use.
CALQUENCE 100 mg twice daily
Induction
Strong CYP3A inducer
Body System
If these inducers cannot be avoided, increase
N=124
Adverse Reactions
CALQUENCE dose to 200 mg twice daily.
All Grades (%)
Grade ≥ 3 (%)
Concomitant Use with Gastric Acid Reducing Agents
Nervous system disorders
Proton Pump Inhibitors: Avoid concomitant use [see Drug Interactions (7) in the full
Headache
39
1.6
Prescribing Information].
Gastrointestinal disorders
H2-Receptor Antagonists: Take CALQUENCE 2 hours before taking a H2-receptor antagonist
Diarrhea
31
3.2
[see Drug Interactions (7) in the full Prescribing Information].
Nausea
19
0.8
Antacids: Separate dosing by at least 2 hours [see Drug Interactions (7) in the full
Prescribing Information].
Abdominal pain
15
1.6
CONTRAINDICATIONS
Constipation
15
None.
Vomiting
13
1.6
WARNINGS AND PRECAUTIONS
General Disorders
Hemorrhage
Fatigue
28
0.8
Serious hemorrhagic events, including fatal events, have occurred in the combined safety
database of 612 patients with hematologic malignancies treated with CALQUENCE
Musculoskeletal and connective tissue disorders
monotherapy. Grade 3 or higher bleeding events, including gastrointestinal, intracranial,
Myalgia
21
0.8
and epistaxis have been reported in 2% of patients. Overall, bleeding events including
Skin & subcutaneous tissue disorders
bruising and petechiae of any grade occurred in approximately 50% of patients with
hematological malignancies.
Bruising†
21
The mechanism for the bleeding events is not well understood. CALQUENCE may further
Rash†
18
0.8
increase the risk of hemorrhage in patients receiving antiplatelet or anticoagulant therapies
Vascular disorders
and patients should be monitored for signs of bleeding. Consider the benefit-risk of
8
0.8
Hemorrhage/Hematoma†
withholding CALQUENCE for 3-7 days pre- and post-surgery depending upon the type of
surgery and the risk of bleeding.
Respiratory, thoracic & mediastinal disorders
Infection
Epistaxis
6
Serious infections (bacterial, viral or fungal), including fatal events and opportunistic
* Per National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) version 4.03.
infections have occurred in the combined safety database of 612 patients with hematologic
†
Bruising: Includes all preferred terms (PTs) containing 'bruise,' 'contusion,' 'petechiae,' or 'ecchymosis'
malignancies treated with CALQUENCE monotherapy. Consider prophylaxis in patients who
Rash: Includes all PTs containing 'rash'
are at increased risk for opportunistic infections.
Hemorrhage/hematoma: Includes all PTs containing 'hemorrhage' or 'hematoma'

American Society of Hematology

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

11/10/17 3:00 PM

http://www.ashacademy.org

Table of Contents for the Digital Edition of ASH News Daily 2017 - Issue 2