AstraZenica
Calquence
First Line of 
Treatment
page 5 of 7
4C
(near CLL-SLL)
CALQUENCE® (acalabrutinib) tablets, for oral use
3
Grade 4 laboratory abnormalities in > 15% of patients treated with 
CALQUENCE plus BR include absolute lymphocyte count decreased 
(26%), absolute neutrophil count decreased (36%), and uric acid 
increased (17%).
Previously Treated Mantle Cell Lymphoma
ACE-LY-004 
The safety data described in this section reflect exposure to 
CALQUENCE (100 mg approximately every 12 hours) in 124 patients 
with previously treated MCL in Trial LY-004 [see Clinical Studies 
(14.2) 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 and discontinuation due to any adverse reaction 
were reported in 1.6% and 6.5% of patients, respectively. 
Tables 7 and 8 present the frequency category of adverse reactions 
observed in patients with MCL treated with CALQUENCE.
Table 7: Non-Hematologic Adverse Reactions in ≥ 5% (All Grades) 
of Patients with MCL in Trial LY-004
Body System 
Adverse Reactions*
CALQUENCE Monotherapy
N=124
All Grades (%)
Grade ≥ 3 (%)
Nervous system disorders
Headache
39
1.6
Gastrointestinal disorders
Diarrhea
31
3.2
Nausea
19
0.8
Abdominal pain
15
1.6
Constipation
15
-
Vomiting
13
1.6
General disorders
Fatigue
28
0.8
Musculoskeletal and connective tissue disorders
Myalgia
21
0.8
Skin and subcutaneous tissue disorders
Bruisinga
21
-
Rashb
18
0.8
Vascular disorders
Hemorrhagec
8
0.8
Respiratory, thoracic and mediastinal disorders
Epistaxis
6
-
* Per NCI CTCAE version 4.03.
a Bruising: Includes all terms containing ‘bruise,’ ‘contusion,’ ‘petechiae,’ or 
‘ecchymosis’.
b Rash: Includes all terms containing ‘rash’.
c Hemorrhage: Includes all terms containing ‘hemorrhage’ or ‘hematoma’.
Table 8: Hematologic Adverse Reactions Reported in ≥ 20% of 
Patients with MCL in Trial LY-004
Hematologic
Adverse Reactions*
CALQUENCE Monotherapy
N=124
All Grades (%)
Grade ≥ 3 (%)
Hemoglobin decreased
46
10
Platelets decreased
44
12
Neutrophils decreased
36
15
*Per NCI CTCAE version 4.03; based on laboratory measurements and 
adverse reactions.
Increases in creatinine to 1.5 to 3 times the upper limit of normal 
(ULN) occurred in 4.8% of patients.
Chronic Lymphocytic Leukemia
The safety data described below reflect exposure to CALQUENCE 
(100 mg approximately every 12 hours, with or without 
obinutuzumab) in 511 patients with CLL from two randomized 
controlled clinical trials [see Clinical Studies (14.3) in the full 
Prescribing Information].
The most common adverse reactions (≥ 30%) of any grade in 
patients with CLL were anemia, neutropenia, thrombocytopenia, 
headache, upper respiratory tract infection, and diarrhea.
ELEVATE-TN
The safety of CALQUENCE plus obinutuzumab (CALQUENCE+G), 
CALQUENCE monotherapy, and obinutuzumab plus chlorambucil 
(GClb) was evaluated in a randomized, multicenter, open-label, 
actively controlled trial in 526 patients with previously untreated 
CLL [see Clinical Studies (14.3) in the full Prescribing Information].
Patients randomized to the CALQUENCE+G arm were treated with 
CALQUENCE and obinutuzumab in combination for six cycles, then 
with CALQUENCE as monotherapy until disease progression or 
unacceptable toxicity. Patients initiated obinutuzumab on Day 1 of 
Cycle 2, continuing for a total of 6 cycles. Patient randomized to 
CALQUENCE monotherapy received CALQUENCE approximately 
every 12 hours until disease progression or unacceptable toxicity. 
The trial required age ≥ 65 years of age or 18 to < 65 years of age 
with a total Cumulative Illness Rating Scale (CIRS) > 6 or creatinine 
clearance of 30 to 69 mL/min, hepatic transaminases ≤ 3 times ULN 
and total bilirubin ≤ 1.5 times ULN, and allowed patients to receive 
antithrombotic agents other than warfarin or equivalent vitamin K 
antagonists.
During randomized treatment, the median duration of exposure to 
CALQUENCE in the CALQUENCE+G and CALQUENCE monotherapy 
arms was 27.7 months (range 0.3 to 40 months), with 95% and 92% 
and 89% and 86% of patients with at least 6 months and 12 months 
of exposure, respectively. In the obinutuzumab and chlorambucil 
arm the median number of cycles was 6 with 84% of patients 
receiving at least 6 cycles of obinutuzumab, 70% of patients received 
at least 6 cycles of chlorambucil. Eighty-five percent of patients in 
the CALQUENCE+G arm received at least 6 cycles of obinutuzumab.
In the CALQUENCE+G and CALQUENCE monotherapy arms, fatal 
adverse reactions that occurred in the absence of disease progression 
and with onset within 30 days of the last study treatment were 
reported in 2% for each treatment arm, most often from infection. 
Serious adverse reactions were reported in 39% of patients in the 
CALQUENCE+G arm and 32% in the CALQUENCE monotherapy arm, 
most often due to events of pneumonia (2.8% to 7%).
In the CALQUENCE+G arm, adverse reactions led to treatment 
discontinuation in 11% of patients and a dose reduction of 
CALQUENCE in 7% of patients. In the CALQUENCE monotherapy 
arm, adverse reactions led to discontinuation in 10% and dose 
reduction in 4% of patients.
Tables 9 and 10 present adverse reactions and laboratory 
abnormalities identified in the ELEVATE-TN trial.
Table 9: Common Adverse Reactions (≥ 15% Any Grade) with 
CALQUENCE in Patients with CLL (ELEVATE-TN)
Body System 
Adverse 
Reaction*
CALQUENCE
plus 
Obinutuzumab
N=178
CALQUENCE
Monotherapy 
N=179
Obinutuzumab 
plus  
Chlorambucil
N=169
All 
Grades
(%)
Grade 
≥ 3
(%)
All 
Grades
(%)
Grade 
≥ 3
(%)
All 
Grades
(%)
Grade 
≥ 3
(%)
Infections
Infection†
69
22‡
65
14‡
46
13‡
Upper respiratory 
tract infection§
39
2.8
35
0
17
1.2
Lower respiratory 
tract infection
a
24
8
18
4.5
7
1.8
Urinary tract 
infection
15
1.7
15
2.8
5
0.6
Blood and lymphatic system disordersb
Neutropenia
c
53
37
23
13
78
50
Anemia
d
52
12
53
10
54
14
Thrombo- 
cytopenia
e
51
12
32
3.4
61
16
Lymphocytosisf
12
11
16
15
0.6
0.6
Nervous system disorders
Headache
40
1.1
39
1.1
12
0
Dizziness
20
0
12
0
7
0
Gastrointestinal disorders
Diarrhea
39
4.5
35
0.6
21
1.8
Nausea
20
0
22
0
31
0
Musculoskeletal and connective tissue disorders
Musculoskeletal 
pain
g
37
2.2
32
1.1
16
2.4
Arthralgia
22
1.1
16
0.6
4.7
1.2
General disorders and administration site conditions
Fatigueh
34
2.2
23
1.1
24
1.2
Skin and subcutaneous tissue disorders
Bruisingi
31
0
21
0
5
0
Rashj
26
2.2
25
0.6
9
0.6
Vascular disorders
Hemorrhagek
20
1.7
20
1.7
6
0
* Per NCI CTCAE version 4.03.
† Includes any adverse reactions involving infection or febrile neutropenia.
‡ Includes 3 fatal cases in the CALQUENCE plus obinutuzumab arm,  
3 fatal cases in the CALQUENCE monotherapy arm and 1 fatal case in the 
obinutuzumab plus chlorambucil arm.
§ Includes upper respiratory tract infection, nasopharyngitis and sinusitis.
a Includes pneumonia, lower respiratory tract infection, bronchitis, bronchiolitis, 
tracheitis, and lung infection.
b Derived from adverse reaction and laboratory data.
c Includes neutropenia, neutrophil count decreased, and related laboratory data.
d Includes anemia, red blood cell count decreased, and related laboratory data.
e Includes thrombocytopenia, platelet count decreased, and related laboratory data.
f Includes lymphocytosis, lymphocyte count increased, and related laboratory data.
g Includes back pain, bone pain, musculoskeletal chest pain, musculoskeletal pain, 
musculoskeletal discomfort, myalgia, neck pain, pain in extremity and spinal pain.
h Includes asthenia, fatigue, and lethargy.
i Includes bruise, contusion, and ecchymosis.
j Includes rash, dermatitis, and other related terms.
k Includes hemorrhage, hematoma, hemoptysis, hematuria, menorrhagia,  
hemarthrosis, and epistaxis.
Other clinically relevant adverse reactions (all grades incidence 
< 15%) in recipients of CALQUENCE (CALQUENCE in combination 
with obinutuzumab and monotherapy) included:
•  Neoplasms: second primary malignancy (10%), non-melanoma 
skin cancer (5%)
•  Cardiac disorders: atrial fibrillation or flutter (3.6%), hypertension 
(5%)
•  Infection: herpesvirus infection (6%)
Table 10: Select Non-Hematologic Laboratory Abnormalities 
(≥ 15% Any Grade), New or Worsening from Baseline in Patients 
Receiving CALQUENCE (ELEVATE-TN) 
Laboratory  
Abnormality*,a
CALQUENCE 
plus 
Obinutuzumab
N=178
CALQUENCE  
Monotherapy
N=179
Obinutuzumab 
plus 
Chlorambucil
N=169
All 
Grades 
(%)
Grade 
≥ 3 
(%)
All 
Grades 
(%)
Grade 
≥ 3 
(%)
All 
Grades 
(%)
Grade 
≥ 3 
(%)
Uric acid increase
29
29
22
22
37
37
ALT increase
30
7
20
1.1
36
6
AST increase
38
5
17
0.6
60
8
Bilirubin increase
13
0.6
15
0.6
11
0.6
*Per NCI CTCAE version 4.03.
a Excludes electrolytes.
Increases in creatinine to 1.5 to 3 times ULN occurred in 3.9% 
and 2.8% of patients in the CALQUENCE combination arm and 
monotherapy arm, respectively.
ASCEND
The safety of CALQUENCE in patients with relapsed or refractory 
CLL was evaluated in a randomized, open-label study (ASCEND) 
[see Clinical Studies (14.3) in the full Prescribing Information]. 
The trial enrolled patients with relapsed or refractory CLL after 
at least one prior therapy and required hepatic transaminases 
≤ 2 times ULN, total bilirubin ≤ 1.5 times ULN, and an estimated 
creatinine clearance ≥ 30 mL/min. The trial excluded patients having 
an absolute neutrophil count < 500/μL, platelet count < 30,000/μL, 
prothrombin time or activated partial thromboplastin time 
> 2 times ULN, significant cardiovascular disease, or a requirement 
for strong CYP3A inhibitors or inducers. Patients were allowed 
to receive antithrombotic agents other than warfarin or equivalent 
vitamin K antagonist.
In ASCEND, 154 patients received CALQUENCE (100 mg approximately 
every 12 hours until disease progression or unacceptable toxicity), 
118 received idelalisib (150 mg approximately every 12 hours until 
disease progression or unacceptable toxicity) with up to 8 infusions 
of a rituximab product, and 35 received up to 6 cycles of 
bendamustine and a rituximab product. The median age overall 
was 68 years (range: 32-90); 67% were male; 92% were white; and 
88% had an ECOG performance status of 0 or 1.
In the CALQUENCE arm, serious adverse reactions occurred in 
29% of patients. Serious adverse reactions in > 5% of patients who 
received CALQUENCE included lower respiratory tract infection 
(6%). Fatal adverse reactions within 30 days of the last dose of 
CALQUENCE occurred in 2.6% of patients, including from second 
primary malignancies and infection.
In recipients of CALQUENCE, permanent discontinuation due to an 
adverse reaction occurred in 10% of patients, most frequently due to 
second primary malignancies followed by infection. Adverse reactions 
led to dosage interruptions of CALQUENCE in 34% of patients, most 
often due to respiratory tract infections followed by neutropenia, and 
dose reduction in 3.9% of patients.
Selected adverse reactions are described in Table 11 and 
non-hematologic laboratory abnormalities are described in Table 12. 
These tables reflect exposure to CALQUENCE with median duration 
of 15.7 months with 94% of patients on treatment for greater than 
6 months and 86% of patients on treatment for greater than 

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