AstraZenica
Calquence
First Line of 
Treatment
page 4 of 7
4C
(near CLL-SLL)
2
CALQUENCE® (acalabrutinib) tablets, for oral use
Refer to the prescribing information of each of the products used 
in combination with CALQUENCE for additional information for 
management of toxicities.
CONTRAINDICATIONS 
None.
WARNINGS AND PRECAUTIONS 
Serious and Opportunistic Infections
Fatal and serious infections, including opportunistic infections, 
have occurred in patients with hematologic malignancies treated 
with CALQUENCE.
Serious or Grade 3 or higher infections (bacterial, viral, or fungal) 
occurred in 29% of 2,055 patients exposed to CALQUENCE in clinical 
trials, most often due to respiratory tract infections (18% of all 
patients, including pneumonia in 14%) [see Adverse Reactions (6.1) 
in the full Prescribing Information]. These infections predominantly 
occurred in the absence of Grade 3 or 4 neutropenia, with 
neutropenic infection reported in 8% of all patients. Opportunistic 
infections in recipients of CALQUENCE have included, but are 
not limited to, hepatitis B virus reactivation, fungal pneumonia, 
Pneumocystis jirovecii pneumonia, Epstein-Barr virus reactivation, 
cytomegalovirus, and progressive multifocal leukoencephalopathy 
(PML). Consider prophylaxis in patients who are at increased risk for 
opportunistic infections. Monitor patients for signs and symptoms 
of infection and treat promptly. 
In an additional cohort of patients receiving CALQUENCE in 
combination with venetoclax with obinutuzumab (AVO) (an 
unapproved regimen for previously untreated CLL/SLL in AMPLIFY), 
serious or Grade 3 or higher infections occurred in 25% receiving AVO 
compared to 14% in patients receiving AV. Fatal infections occurred in 
6% receiving AVO compared to 3.1% of patients receiving AV, most 
commonly due to COVID-19. The safety and effectiveness of AVO has 
not been established in patients with previously untreated CLL/SLL 
[see Clinical Studies (14.3) in the full Prescribing Information].
Hemorrhage 
Fatal and serious hemorrhagic events have occurred in patients 
treated with CALQUENCE. Major hemorrhage (serious or Grade 3 
or higher bleeding or any central nervous system bleeding) 
occurred in 4.7% of patients, with fatal hemorrhage occurring in 
0.1% of 2,055 patients exposed to CALQUENCE in clinical trials. 
Bleeding events of any grade, excluding bruising and petechiae, 
occurred in 39% of patients [see Adverse Reactions (6.1) in the full 
Prescribing Information].
Use of antithrombotic agents concomitantly with CALQUENCE may 
further increase the risk of hemorrhage. In clinical trials, major 
hemorrhage occurred in 5% of patients taking CALQUENCE without 
antithrombotic agents and 3.2% of patients taking CALQUENCE 
with antithrombotic agents. Consider the risks and benefits of 
antithrombotic agents when co-administered with CALQUENCE. 
Monitor patients for signs of bleeding. 
Consider the benefit-risk of withholding CALQUENCE for 3 to 7 
days pre- and post-surgery depending upon the type of surgery 
and the risk of bleeding.
Cytopenias 
CALQUENCE can cause Grade 3 or 4 cytopenias. Grade 3 or 4 
cytopenias included absolute neutrophil count decreased (28%), 
absolute lymphocyte count decreased (10%), hemoglobin 
decreased (9%), and platelets decreased (9%) in 1,758 patients 
treated with CALQUENCE alone and in combination with 
obinutuzumab or venetoclax; Grade 4 neutropenia developed in 14% 
[see Adverse Reactions (6.1) in the full Prescribing Information].
Monitor complete blood counts regularly during treatment. Interrupt 
treatment, reduce the dose, or discontinue treatment as warranted 
[see Dosage and Administration (2.3) in the full Prescribing 
Information].
Second Primary Malignancies 
Second primary malignancies, including skin cancers and other 
solid tumors, occurred in 16% of 2,055 patients exposed to 
CALQUENCE in clinical trials [see Adverse Reactions (6.1) in the 
full Prescribing Information]. The most frequent second primary 
malignancy was non-melanoma skin cancer, reported in 9% of 
patients, followed by other solid tumors in 8% (including melanoma, 
lung cancer, gastrointestinal cancers, and genitourinary cancers) and 
hematologic malignancies (1.1%). Fatal second primary malignancies 
occurred in 0.8% of patients. Monitor patients for the development of 
second cancers and advise protection from sun exposure.
Cardiac Arrhythmias
Fatal and serious cardiac arrhythmias have occurred in patients 
treated with CALQUENCE. Grade 3 or 4 atrial fibrillation or flutter was 
reported in 2.2% of 2,055 patients treated with CALQUENCE, with 
all grades of atrial fibrillation or flutter reported in 7% of all patients 
[see Adverse Reactions (6.1) in the full Prescribing Information]. 
Grade 3 or higher ventricular arrhythmia events were reported in 
0.5% of patients, including fatal cases in 0.3% of all patients. The 
risk of arrhythmias may be increased in patients with cardiac risk 
factors, hypertension, previous arrhythmias, and acute infection. 
Monitor for symptoms of arrhythmia (e.g., palpitations, dizziness, 
syncope, dyspnea) and manage as appropriate.
Hepatotoxicity, Including Drug-Induced Liver Injury
Hepatotoxicity, including severe, life-threatening, and potentially 
fatal cases of drug-induced liver injury (DILI), has occurred in 
patients treated with Bruton tyrosine kinase inhibitors, including 
CALQUENCE.
Evaluate bilirubin and transaminases at baseline and throughout 
treatment with CALQUENCE. For patients who develop abnormal 
liver tests after CALQUENCE, monitor more frequently for liver test 
abnormalities and clinical signs and symptoms of hepatic toxicity. If 
DILI is suspected, withhold CALQUENCE. Upon confirmation of DILI, 
discontinue CALQUENCE.
ADVERSE REACTIONS 
The following clinically significant adverse reactions are discussed 
in greater detail in other sections of the labeling:
•  Serious and Opportunistic Infections [see Warnings and 
Precautions (5.1) in the full Prescribing Information]
•  Hemorrhage [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] 
•  Cardiac Arrhythmias [see Warnings and Precautions (5.5) in 
the full Prescribing Information]
•  Hepatotoxicity, including DILI [see Warnings and Precautions 
(5.6) in the full Prescribing Information]
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 practice.
The data in the Warnings and Precautions reflect exposure to 
CALQUENCE 100 mg approximately every 12 hours in 2,055 patients 
with hematologic malignancies. Treatment includes CALQUENCE 
monotherapy in 1258 patients in 9 trials, and CALQUENCE 
combinations in 797 patients in 4 trials. Among these recipients of 
CALQUENCE, 89% were exposed for at least 6 months and 82% 
were exposed for at least one year. In this pooled safety population, 
adverse reactions in ≥ 30% of 2,055 patients, excluding laboratory 
abnormalities, were upper respiratory tract infection (37%), 
diarrhea (36%), headache (35%), and musculoskeletal pain (32%). 
The most common Grade 3 or 4 laboratory abnormalities (≥ 10%) 
were absolute neutrophil count decreased (32%), uric acid 
increased (27%), absolute lymphocyte count decreased (21%) 
and platelets decreased (10%).
Previously Untreated Mantle Cell Lymphoma
The safety data described below reflect exposure to CALQUENCE 
(100 mg approximately every 12 hours, with or without BR) in 
patients with MCL [see Clinical Studies (14.1) in the full Prescribing 
Information].
ECHO
The safety of CALQUENCE in combination with bendamustine and 
rituximab (CALQUENCE plus BR) was evaluated in 297 patients with 
previously untreated MCL in ECHO [see Clinical Studies (14.1) in 
the full Prescribing Information]. The trial enrolled patients with 
previously untreated MCL, ≥ 65 years of age with no intention for 
transplant, total bilirubin ≤ 1.5 × ULN, AST or ALT ≤ 2.5 × ULN, and 
estimated creatinine clearance of > 50 mL/min. Patients received 6 
cycles (as 28-day cycles) of CALQUENCE 100 mg orally twice daily 
(n = 297) or placebo (n = 297) in combination with bendamustine 
and rituximab. Patients then received CALQUENCE 100 mg orally 
twice daily or placebo continuously until progressive disease or 
unacceptable toxicity, with 12 additional dosages of rituximab every 
other cycle up to Cycle 30.
The median duration of treatment with CALQUENCE was 28.6 
months. A total of 171 (57.6%) patients were treated with 
CALQUENCE for > 24 months and 122 (41.1%) patients were treated 
for > 36 months.
Serious adverse reactions occurred in 69% of patients who received 
CALQUENCE plus BR. Serious adverse reactions reported in ≥ 2% 
of patients were pneumonia (23%; includes COVID-19 pneumonia), 
COVID-19 (20%; includes COVID-19 pneumonia), pyrexia (6%), 
second primary malignancy (7%), rash (3.4%), febrile neutropenia 
(3.4%), atrial fibrillation (3%), sepsis (2.7%), and anemia (2.4%). 
Fatal adverse reactions that occurred within 30 days of the last 
study treatment were reported in 12% who received CALQUENCE 
plus BR including COVID-19 (6%; includes COVID-19 pneumonia), 
pneumonia (1%), sepsis (0.3%), second primary malignancy 
(0.7%), and pneumonitis (0.3%).
Adverse reactions led to permanent discontinuation of CALQUENCE 
in 43%, dosage interruptions in 74%, and dosage reductions in 
10% of patients. Adverse reactions that resulted in dosage 
modification in > 10% included infections, cytopenias, rashes, 
and gastrointestinal toxicity. Adverse reactions which resulted in 
permanent discontinuation of CALQUENCE in ≥ 4% of patients 
included COVID-19 (includes COVID-19 pneumonia) and neutropenia.
Table 5 and Table 6 summarize select adverse reactions and 
laboratory abnormalities observed in patients treated in ECHO.
Table 5: Adverse Reactions* (≥ 15%) in Patients with Previously 
Untreated MCL Who Received CALQUENCE plus BR in ECHO
Body System 
Adverse Reactions*
CALQUENCE 
plus BR 
N = 297
Placebo 
plus BR 
N = 297
All 
Grades 
(%)
Grade
3 or 4 
(%)
All 
Grades 
(%)
Grade
3 or 4 
(%)
Skin and subcutaneous tissue disorders
Rasha
47
12
31
3
Infections
COVID-19b
38
13
27
11
Upper respiratory tract infectionc
30
0.7
29
1
Pneumoniad
31
17
25
14
Gastrointestinal disorders
Diarrhea
37
3
28
2.4
Vomiting
26
0.7
14
1
Constipation
25
1
25
0.3
General disorders
Fatigue
37
3.7
32
4.4
Pyrexia
29
2.4
24
1.3
Edema
20
1.3
19
0
Nervous system disorders
Headache
31
1.7
14
0.7
Dizziness
18
1
17
0.3
Respiratory, thoracic and mediastinal disorders
Cough
27
0
20
0.3
Dyspnea
17
1
11
2.7
Neoplasms
Secondary primary malignancye
19
7
15
7
Musculoskeletal and connective tissue disorders
Arthralgia
18
0.7
16
1
Vascular disorders
Hemorrhagef
20
1.7
11
3
*Excludes laboratory terms.
a Includes rash, dermatitis, and other related terms.
b Includes the following fatal adverse reactions: n=24 for COVID-19.
c Includes upper respiratory tract infection, sinusitis, pharyngitis, and  
related terms.
d Includes pneumonia, terms containing pneumonia, and related infections. 
COVID-19 pneumonia is represented under both Pneumonia and COVID-19.
e Includes terms related to malignant neoplasms including cutaneous  
neoplasms.
f Includes all terms containing hematoma or hemorrhage and related terms 
indicative of bleeding.
Clinically relevant adverse reactions in < 15% of patients receiving 
CALQUENCE plus BR included bruising, abdominal pain, atrial fibrillation 
or flutter, and tumor lysis syndrome.
Table 6: Select Laboratory Abnormalities (≥ 15%) in Patients with 
Previously Untreated MCL in ECHO
Laboratory Abnormality
CALQUENCE 
plus BRa
Placebo 
plus BRa
All 
grade 
(%)
Grade
3 or 4 
(%)
All 
grade 
(%)
Grade
3 or 4 
(%)
Hematologic Abnormalities
Lymphocytes decreased
98
87
97
89
Hemoglobin decreased
80
11
65
11
Neutrophils decreased
76
56
77
51
Platelets decreased
69
18
60
16
Chemistry Abnormalities
AST increased
53
5
50
3.4
Uric acid increased
45
45
40
40
ALT increased
44
7
41
2.4
Potassium increased
40
2
38
2.7
Creatinine increased
37
3
28
2.4
Phosphate decreased
36
4.4
30
4.7
Potassium decreased
29
7
23
6
Bilirubin increased
19
2
12
2
a The denominator used to calculate the rate varied between 296 and 297 
based on the number of patients with a baseline value and at least one 
post-treatment value.

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