Previously Untreated CLL

SAFETY

PREVIOUSLY UNTREATED CLL

ADVERSE REACTIONS

Safety and tolerability consistent with the established profile of CALQUENCE

Common adverse reactions (≥15%, any grade) with CALQUENCE in ELEVATE-TN*1

Common adverse reactions reported in patients with CLL in ELEVATE-TN

Select non-hematologic laboratory abnormalities (≥15%, any grade), new or worsening from baseline with CALQUENCE in ELEVATE-TN*1

Non-Hematologic laboratory abnormalities with CLL in ELEVATE-TN

Increases in creatinine 1.5 to 3 times the upper limit of normal occurred in 3.9% and 2.8% of patients in the CALQUENCE + obinutuzumab and CALQUENCE monotherapy arms, respectively.1

*The median duration of exposure to CALQUENCE in the CALQUENCE + obinutuzumab and CALQUENCE monotherapy arms was 27.7 months (range: 0.3 to 40 months).1

Includes multiple adverse drug reaction terms (see full Prescribing Information).1

Includes 3 fatal cases in the CALQUENCE + obinutuzumab arm, 3 fatal cases in the CALQUENCE monotherapy arm, and 1 fatal case in the GClb arm.1

§Excludes electrolytes.1

ALT=alanine aminotransferase; AST=aspartate aminotransferase; GClb=obinutuzumab + chlorambucil.

MOST ADVERSE REACTIONS WERE GRADE 1 OR 2

Select adverse reactions for CALQUENCE + obinutuzumab (n=178)||1,2

Select Adverse Reactions with CALQUENCE + obinutuzumab (N=178) Select Adverse Reactions with CALQUENCE + obinutuzumab (N=178)

Other clinically relevant adverse reactions (<15%, any grade) in recipients of CALQUENCE (CALQUENCE + obinutuzumab and as monotherapy) included1:

  • Neoplasms: second primary malignancy (10%), including non-melanoma skin cancer (5%)
  • Infection: herpesvirus infection (6%)
  • Cardiac disorders: atrial fibrillation or flutter (3.6%), hypertension (5%)

In the CALQUENCE + obinutuzumab 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 + obinutuzumab arm and 32% in the CALQUENCE monotherapy arm, most often due to events of pneumonia (7% and 2.8%, respectively).1

||Infusion-related reactions were reported in 14% of patients in the CALQUENCE + obinutuzumab arm and 39% of patients in the GClb arm.2

DISCONTINUATION RATES

FEW PATIENTS DISCONTINUED CALQUENCE DUE TO ADVERSE REACTIONS AT MEDIAN 28.3-MONTH FOLLOW-UP1

Discontinuation rate of CALQUENCE due to adverse reactions in ELEVATE-TN
Discontinuation rate of CALQUENCE monotherapy due to adverse reactions in ELEVATE-TN

RELAPSED/REFRACTORY CLL

ADVERSE REACTIONS

Safety and tolerability consistent with the established profile of CALQUENCE

Common adverse reactions (≥15%, any grade) with CALQUENCE in ASCEND*1

Common adverse reactions of patients with CLL in ASCEND

Select non-hematologic laboratory abnormalities (≥10%, any grade), new or worsening from baseline with CALQUENCE in ASCEND*1

Non-Hematologic laboratory abnormalities  with CLL in ASCEND

Increases in creatinine 1.5 to 3 times the upper limit of normal occurred in 1.3% of patients who received CALQUENCE.1

*The median duration of exposure to CALQUENCE was 15.7 months.1

Includes multiple adverse drug reaction terms (see full Prescribing Information).1

Includes 1 fatal case in the CALQUENCE monotherapy arm and 1 fatal case in the IR arm.1

§Excludes electrolytes.1

BR=bendamustine + rituximab; IR=idelalisib + rituximab.

MOST ADVERSE REACTIONS WERE GRADE 1 OR 2

Select adverse reactions for CALQUENCE (n=154)1,2

Select Adverse Reactions of CALQUENCE in ASCEND Select Adverse Reactions of CALQUENCE in ASCEND

||Excludes dermatitis and other related terms.

Clinically relevant adverse reactions (<15%, any grade) in recipients of CALQUENCE included1:

  • Skin and subcutaneous disorders: bruising (10%), rash (9%)
  • Neoplasms: second primary malignancy (12%), including non-melanoma skin cancer (6%)
  • Musculoskeletal and connective tissue disorders: arthralgia (8%)
  • Cardiac disorders: atrial fibrillation or flutter (5%), hypertension (3.2%)
  • Infection: herpesvirus infection (4.5%)

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.1

DISCONTINUATION RATES

FEW PATIENTS DISCONTINUED CALQUENCE DUE TO ADVERSE REACTIONS AT MEDIAN 16.1-MONTH FOLLOW-UP1

Discontinuation rate of CALQUENCE due to adverse reactions in ASCEND
-

IMPORTANT SAFETY INFORMATION ABOUT CALQUENCE® (acalabrutinib) capsules

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 19% of 1029 patients exposed to CALQUENCE in clinical trials, most often due to respiratory tract infections (11% of all patients, including pneumonia in 6%). These infections predominantly occurred in the absence of Grade 3 or 4 neutropenia, with neutropenic infection reported in 1.9% of all patients. Opportunistic infections in recipients of CALQUENCE have included, but are not limited to, hepatitis B virus reactivation, fungal pneumonia, Pneumocystis jiroveci 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.

Hemorrhage

Fatal and serious hemorrhagic events have occurred in patients with hematologic malignancies treated with CALQUENCE. Major hemorrhage (serious or Grade 3 or higher bleeding or any central nervous system bleeding) occurred in 3.0% of patients, with fatal hemorrhage occurring in 0.1% of 1029 patients exposed to CALQUENCE in clinical trials. Bleeding events of any grade, excluding bruising and petechiae, occurred in 22% of patients.

Use of antithrombotic agents concomitantly with CALQUENCE may further increase the risk of hemorrhage. In clinical trials, major hemorrhage occurred in 2.7% of patients taking CALQUENCE without antithrombotic agents and 3.6% 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 3-7 days pre- and post-surgery depending upon the type of surgery and the risk of bleeding.

Cytopenias

Grade 3 or 4 cytopenias, including neutropenia (23%), anemia (8%), thrombocytopenia (7%), and lymphopenia (7%), developed in patients with hematologic malignancies treated with CALQUENCE. Grade 4 neutropenia developed in 12% of patients. Monitor complete blood counts regularly during treatment. Interrupt treatment, reduce the dose, or discontinue treatment as warranted.

Second Primary Malignancies

Second primary malignancies, including skin cancers and other solid tumors, occurred in 12% of 1029 patients exposed to CALQUENCE in clinical trials. The most frequent second primary malignancy was skin cancer, reported in 6% of patients. Monitor patients for skin cancers and advise protection from sun exposure.

Atrial Fibrillation and Flutter

Grade 3 atrial fibrillation or flutter occurred in 1.1% of 1029 patients treated with CALQUENCE, with all grades of atrial fibrillation or flutter reported in 4.1% of all patients. The risk 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.

ADVERSE REACTIONS

The most common adverse reactions (≥ 30%) of any grade in patients with CLL were anemia,* neutropenia,* thrombocytopenia,* headache, upper respiratory tract infection, and diarrhea.

*Treatment-emergent decreases (all grades) of hemoglobin, platelets, and neutrophils were based on laboratory measurements and adverse reactions.

In patients with previously untreated CLL exposed to CALQUENCE, 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 plus obinutuzumab arm and 32% in the CALQUENCE monotherapy arm, most often due to events of pneumonia (7% and 2.8%, respectively).

Adverse reactions led to CALQUENCE dose reduction in 7% and 4% of patients in the CALQUENCE plus obinutuzumab arm (N=178) and CALQUENCE monotherapy arm (N=179), respectively. Adverse events led to discontinuation in 11% and 10% of patients, respectively. Increases in creatinine 1.5 to 3 times the upper limit of normal occurred in 3.9% and 2.8% of patients in the CALQUENCE combination arm and monotherapy arm, respectively.

In patients with relapsed/refractory CLL exposed to CALQUENCE, 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.

Adverse reactions led to CALQUENCE dose reduction in 3.9% of patients (N=154), dosage interruptions in 34% of patients, most often due to respiratory tract infections followed by neutropenia, and discontinuation in 10% of patients, most frequently due to second primary malignancies followed by infection. Increases in creatinine 1.5 to 3 times the upper limit of normal occurred in 1.3% of patients who received CALQUENCE.

DRUG INTERACTIONS

Strong CYP3A Inhibitors: Avoid co-administration with a strong CYP3A inhibitor. If a strong CYP3A inhibitor will be used short-term, interrupt CALQUENCE.

Moderate CYP3A Inhibitors: When CALQUENCE is co-administered with a moderate CYP3A inhibitor, reduce CALQUENCE dose to 100 mg once daily.

Strong CYP3A Inducers: Avoid co-administration with a strong CYP3A inducer. If a strong CYP3A inducer cannot be avoided, increase the CALQUENCE dose to 200 mg approximately every 12 hours.

Gastric Acid Reducing Agents: If treatment with a gastric acid reducing agent is required, consider using an H2-receptor antagonist or an antacid. Take CALQUENCE 2 hours before taking an H2-receptor antagonist. Separate dosing with an antacid by at least 2 hours.

Avoid co-administration with proton pump inhibitors. Due to the long-lasting effect of proton pump inhibitors, separation of doses may not eliminate the interaction with CALQUENCE.

SPECIFIC POPULATIONS

Based on findings in animals, CALQUENCE may cause fetal harm and dystocia when administered to a pregnant woman. There are no available data in pregnant women to inform the drug-associated risk. Advise pregnant women of the potential risk to a fetus.

Pregnancy testing is recommended for females of reproductive potential prior to initiating CALQUENCE therapy. Advise female patients of reproductive potential to use effective contraception during treatment with CALQUENCE and for at least 1 week following the last dose of CALQUENCE.

It is not known if CALQUENCE is present in human milk. Advise lactating women not to breastfeed while taking CALQUENCE and for at least 2 weeks after the final dose.

Avoid administration of CALQUENCE in patients with severe hepatic impairment. Dose modifications are not required for patients with mild or moderate hepatic impairment.

INDICATION AND USAGE

CALQUENCE is indicated for the treatment of adult patients with chronic lymphocytic leukemia (CLL) or small lymphocytic lymphoma (SLL).

Please see full Prescribing Information, including Patient Information.

You may report side effects related to AstraZeneca products by clicking here.

Reference: 1. CALQUENCE [package insert]. Wilmington, DE: AstraZeneca Pharmaceuticals LP; 2019.

References: 1. CALQUENCE [package insert]. Wilmington, DE: AstraZeneca Pharmaceuticals LP; 2019. 2. Data on File, REF-64711. AstraZeneca Pharmaceuticals LP. 3. Elevate CLL TN: study of obinutuzumab + chlorambucil, acalabrutinib (ACP-196) + obinutuzumab, and acalabrutinib in subjects with previously untreated CLL. ClinicalTrials.gov identifier: NCT02475681. https://clinicaltrials.gov/ct2/show/NCT02475681. Updated October 14, 2019. Accessed November 14, 2019. 4. Sharman JP, Banerji V, Fogliatto LM, et al. ELEVATE TN: phase 3 study of acalabrutinib combined with obinutuzumab (O) or alone vs O plus chlorambucil (Clb) in patients (pts) with treatment-naive chronic lymphocytic leukemia (CLL). Abstract for American Society of Hematology Annual Meeting; December 7-10, 2019; Orlando, FL. 5. A study of acalabrutinib vs investigator’s choice of idelalisib plus rituximab or bendamustine plus rituximab in R/R CLL. ClinicalTrials.gov identifier: NCT02970318. https://clinicaltrials.gov/ct2/show/NCT02970318. Updated August 16, 2019. Accessed November 14, 2019. 6. Ghia P, Pluta A, Watch M, et al. ASCEND phase 3 study of acalabrutinib vs investigator's choice of rituximab plus idelalisib (IDR) or bendamustine (BR) in patients with relapsed/refractory (R/R) chronic lymphocytic leukemia (CLL). Presented at: 24th European Hematology Society Congress; June 13-16, 2019; Amsterdam, the Netherlands.

References: 1. CALQUENCE [package insert]. Wilmington, DE: AstraZeneca Pharmaceuticals LP; 2019. 2. Data on File, REF-64711. AstraZeneca Pharmaceuticals LP.

Reference: 1. CALQUENCE [package insert]. Wilmington, DE: AstraZeneca Pharmaceuticals LP; 2019.

+

IMPORTANT SAFETY INFORMATION ABOUT CALQUENCE® (acalabrutinib) capsules

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 19% of 1029 patients exposed to CALQUENCE in clinical trials, most often due to respiratory tract infections (11% of all patients, including pneumonia in 6%). These infections predominantly occurred in the absence of Grade 3 or 4 neutropenia, with neutropenic infection reported in 1.9% of all patients. Opportunistic infections in recipients of CALQUENCE have included, but are not limited to, hepatitis B virus reactivation, fungal pneumonia, Pneumocystis jiroveci 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.