CALQUENCE® (acalabrutinib) 100 mg tablets

Prescribing Information
Important Safety Information
Colorado WAC Disclosure

The #1-prescribed BTKi for patients starting CLL treatment*5

CARDIOVASCULAR SAFETY DATA IN CLL WITH 6 YEARS OF FOLLOW-UP†1

Dear Healthcare Professional,

At the 2023 American Society of Hematology (ASH) Annual Meeting, a 6‑year follow‑up analysis of ELEVATE‑TN, a Phase 3 trial of CALQUENCE ± obinutuzumab vs chemoimmunotherapy in treatment‑naive patients with CLL, was presented.1

Scroll down to see full Important Safety Information about CALQUENCE below


	Low rates of atrial fibrillation, hypertension, and Grade ≥3 bleeding at 6-year median follow-up1-3

Select AEs for CALQUENCE monotherapy (n=179)‡1-3

A table showing select cardiovascular AE’s for CALQUENCE monotherapy

The incidence rates (any grade) in the CALQUENCE + obinutuzumab arm (n=178) (2-year/4-year/6-year analysis) were atrial fibrillation
(3.4%/3.9%/7%), hypertension (7%/8%/11%), and bleeding (Grade ≥3)
(1.7%/2.8%/7%).1-3

In a pooled analysis of 1029 patients treated with CALQUENCE, Grade 3 or higher ventricular arrhythmia events were reported in 0.9% of patients.4

The 46.9-month and 74.5-month median follow-up data from ELEVATE-TN are not included in the Prescribing Information for CALQUENCE.

Interested in more long-term safety data?


	ADDITIONAL SAFETY RESULTS AND STUDY DESIGN

	The most common AEs at 6-year median follow-up were consistent with those observed at 28.3-month and 46.9-month median follow-up.¶1,3,4

	At 74.5-month median follow-up:

	The most common AEs (≥30%) of any grade in either arm in patients treated with CALQUENCE + obinutuzumab (n=178)/CALQUENCE monotherapy (n=179) were infection (83%/80%), bleeding (53%/45%), diarrhea (44%/43%), headache (40%/39%), arthralgia (36%/27%), neutropenia (34%/13%), and fatigue (31%/24%).1

	The median duration of exposure was 74.4 months with CALQUENCE + obinutuzumab and 72.0 months with CALQUENCE monotherapy.1

	At 46.9-month median follow-up:

	The most common ARs (≥30%) of any grade in either arm in patients treated with CALQUENCE + obinutuzumab (n=178)/CALQUENCE monotherapy (n=179) were infection (75%/74%), bleeding (47%/42%), diarrhea (41%/40%), headache (40%/38%), and neutropenia (34%/12%).3

	The median duration of exposure with CALQUENCE + obinituzumab was 46.6 months and 45.7 months with CALQUENCE monotherapy.3

	At 28.3-month median follow-up:

	The most common ARs (≥30%) of any grade in either arm in patients treated with CALQUENCE + obinutuzumab (n=178)/CALQUENCE monotherapy (n=179) were infection (69%/65%), including upper respiratory tract infection (39%/35%), neutropenia (53%/23%), anemia (52%/53%), thrombocytopenia (51%/32%), headache (40%/39%), diarrhea (39%/35%), musculoskeletal pain (37%/32%), fatigue (34%/23%), and bruising (31%/21%).4

	The median duration of exposure with CALQUENCE + obinutuzumab was 27.7 months and 27.7 months with CALQUENCE monotherapy.4

	About ELEVATE-TN

	ELEVATE-TN was a Phase 3, open-label, randomized, multicenter trial in 535 patients with previously untreated CLL evaluating CALQUENCE ± obinutuzumab vs GClb.1,4 Patients were randomized 1:1:1 to receive either CALQUENCE + obinutuzumab (n=179), CALQUENCE monotherapy (n=179), or obinutuzumab + chlorambucil (maximum 6 cycles; n=177). Patients received CALQUENCE 100 mg orally approximately every 12 hours until disease progression or unacceptable toxicity for either CALQUENCE + obinutuzumab or CALQUENCE monotherapy. The primary endpoint was IRC-assessed PFS for CALQUENCE + obinutuzumab vs GClb. Select secondary endpoints at interim analysis were IRC-assessed PFS (CALQUENCE monotherapy vs GClb), IRC-assessed ORR, OS, and safety. After the interim analysis of 28.3 months, PFS and ORR were INV-assessed only.

	*Based on January 2024 IMS New Patient Starts claims data.5 †At 74.5-month median follow-up (range: 0.0-89.0 months).1 ‡Values >5% are rounded to the nearest whole number.1-3 § 28.3-month (range: 0.0-40.8 months), 46.9-month (range: 0.0-59.4 months), and 74.5-month (range: 0.0-89.0 months) median follow-ups are rounded to the nearest year.1-3 \|\|Defined as any serious or Grade ≥3 hemorrhagic event in the central nervous system.2 ¶Apart from COVID-19, which was observed during the pandemic.1

	AEs=adverse events; ARs=adverse reactions; BTKi=Bruton tyrosine kinase inhibitor; CLL=chronic lymphocytic leukemia; CV=cardiovascular; GClb=obinutuzumab + chlorambucil; INV=investigator; IRC=independent review committee; ORR=overall response rate; OS=overall survival; PFS=progression-free survival.

INDICATION AND USAGE

CALQUENCE is a Bruton tyrosine kinase (BTK) inhibitor indicated for the treatment of adult patients with chronic lymphocytic leukemia (CLL) or small lymphocytic lymphoma (SLL).

IMPORTANT SAFETY INFORMATION ABOUT CALQUENCE® (acalabrutinib) tablets

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 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.

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.

Cardiac Arrhythmias

Serious cardiac arrhythmias have occurred in patients treated with CALQUENCE. 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. Grade 3 or higher ventricular arrhythmia events were reported in 0.9% of patients. The risk may be increased in patients with cardiac risk factors, hypertension, previous arrhythmias, and acute infection. Monitor for symptoms of arrhythmia (eg, 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 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 to 1.5 to 3 times the upper limit of normal (ULN) 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), dose 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 to 1.5 to 3 times ULN occurred in 1.3% of patients who received CALQUENCE.

DRUG INTERACTIONS

Strong CYP3A Inhibitors: Avoid co-administration of CALQUENCE with a strong CYP3A inhibitor. If these inhibitors will be used short-term, interrupt CALQUENCE. After discontinuation of strong CYP3A inhibitor for at least 24 hours, resume previous dosage of CALQUENCE.

Moderate CYP3A Inhibitors: Reduce the dosage of CALQUENCE to 100 mg once daily when co-administered with a moderate CYP3A inhibitor.

Strong CYP3A Inducers: Avoid co-administration of CALQUENCE with a strong CYP3A inducer. If co-administration is unavoidable, increase the dosage of CALQUENCE to 200 mg approximately every 12 hours.

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 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 2 weeks after the last dose.

Avoid use of CALQUENCE in patients with severe hepatic impairment (Child-Pugh class C). No dosage adjustment of CALQUENCE is recommended in patients with mild (Child‑Pugh class A) or moderate (Child-Pugh class B) hepatic impairment.

Please see full Prescribing Information, including Patient Information.

You may report side effects related to AstraZeneca products.


	References: 1. Sharman JP, Egyed M, Jurczak W, et al. Acalabrutinib ± obinutuzumab vs obinutuzumab + chlorambucil in treatment-naive chronic lymphocytic leukemia: 6-year follow-up of ELEVATE-TN [presentation]. Presented at: American Society of Hematology (ASH) Annual Meeting; December 9-12, 2023. San Diego, CA. Abs 636. 2. Sharman JP, Egyed M, Jurczak W, et al. Acalabrutinib with or without obinutuzumab versus chlorambucil and obinutuzumab for treatment-naive chronic lymphocytic leukemia (ELEVATE-TN): a randomized, controlled, phase 3 trial [published correction appears in Lancet. 2020;395(10238):1694]. Lancet. 2020;395(10232):1278-1291 and supplementary appendix. 3. Sharman JP, Egyed M, Jurczak W, et al. Acalabrutinib ± obinutuzumab vs obinutuzumab + chlorambucil in treatment‑naive chronic lymphocytic leukemia: ELEVATE‑TN 4‑year follow‑up. Poster presented at: American Society of Clinical Oncology (ASCO) Annual Meeting; ‌Ju‌ne ‌4-‌8‌, 2‌02‌1 (Virtual meeting). 4. CALQUENCE [package insert]. Wilmington, DE: AstraZeneca Pharmaceuticals LP; 2024. 5. Data on File, US-87087. AstraZeneca Pharmaceuticals LP.

CALQUENCEhcp.com

Prescribing Information

This product information is intended for US health care professionals only.

CALQUENCE is a registered trademark of the AstraZeneca group of companies.

AstraZeneca
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