The #1 prescribed BTKi for patients starting CLL treatment*3

Dear Healthcare Professional,

At the interim analysis, PFS risk reduction vs GClb at 28.3‑month median follow-up was 90% with CALQUENCE + obinutuzumab† (HR=0.10‡ [95% CI: 0‌.‌0‌6‌-‌0‌.‌1‌7‌]; P<0.0001§ ) and 80% with CALQUENCE monotherapy (HR=0.20‡ [95% CI: 0‌.‌1‌3‌-‌0‌.‌3‌0‌], P<0.0001§).1,2

Additional ELEVATE-TN data at 6-year median follow-up in 1L CLL were published in Blood.||1,2

86% risk reduction in disease progression or death with CALQUENCE + obinutuzumab vs GClb at 74.5‑month median follow-up||¶2

Investigator‑assessed PFS at 6‑year median follow‑up¶2

Median PFS was not reached with CALQUENCE ± obinutuzumab and was 27.8 months with GClb.2

The 74.5-month median follow-up data are not in the Prescribing Information. The analysis was descriptive in nature.

SAFETY RESULTS AND STUDY DESIGN

The most common AEs at 6-year median follow-up were consistent with those observed at interim analysis at 28.3-month median follow-up.**1,2

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%).2

The median duration of exposure was 74.4 months with CALQUENCE + obinutuzumab and 72.0 months with CALQUENCE monotherapy.2

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%). 1

The median duration of exposure with CALQUENCE + obinutuzumab was 27.7 months and 27.7 months with CALQUENCE monotherapy.1

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.1,2 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.

AEs=adverse events; ARs=adverse reactions; BTKi=Bruton tyrosine kinase inhibitor; CI=confidence interval; CLL=chronic lymphocytic leukemia; GClb=obinutuzumab + chlorambucil; HR=hazard ratio; 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 32% of 1,764 patients exposed to CALQUENCE in clinical trials, most often due to respiratory tract infections (19% of all patients, including pneumonia in 9%). These infections predominantly occurred in the absence of Grade 3 or 4 neutropenia, with neutropenic infection reported in 2.7% 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 treated with CALQUENCE. Major hemorrhage (serious or Grade 3 or higher bleeding or any central nervous system bleeding) occurred in 4.4% of patients, with fatal hemorrhage occurring in 0.2% of 1,764 patients exposed to CALQUENCE in clinical trials. Bleeding events of any grade, excluding bruising and petechiae, occurred in 40% of patients.

Use of antithrombotic agents concomitantly with CALQUENCE may further increase the risk of hemorrhage. In clinical trials, major hemorrhage occurred in 7% of patients taking CALQUENCE without antithrombotic agents and 4% 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 (26%), platelets decreased (10%), hemoglobin decreased (10%), and absolute lymphocyte count decreased (10%) in patients treated with CALQUENCE alone or in combination with obinutuzumab; Grade 4 neutropenia developed in 14% 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 18% of 1,764 patients exposed to CALQUENCE in clinical trials. The most frequent second primary malignancy was non-melanoma skin cancer, reported in 10% of patients, followed by other solid tumors in 9% (including melanoma, lung cancer, gastrointestinal cancers, and genitourinary cancers) and hematologic malignancies (1%). 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 2.6% of 1,764 patients treated with CALQUENCE, with all grades of atrial fibrillation or flutter reported in 7% of all patients. Grade 3 or higher ventricular arrhythmia events were reported in 0.6% 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 (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 exposed to CALQUENCE were anemia,* neutropenia,* thrombocytopenia,* headache, upper respiratory tract infection, and diarrhea.

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 (2.8% to 7%).

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.

References: 1. CALQUENCE® (acalabrutinib) tablets [prescribing information]. Wilmington, DE: AstraZeneca Pharmaceuticals LP; 2025. 2. Sharman JP, Egyed M, Jurczak W, et al. Acalabrutinib-Obinutuzumab Improves Survival vs Chemoimmunotherapy in treatment-naive CLL in the 6-year Follow-up of ELEVATE-TN [article and supplementary appendix]. Blood. Published online April 8, 2025. 3. Data on File. US-100665. AstraZeneca Pharmaceuticals LP.

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