INDICATION AND USAGE

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

SELECT SAFETY INFORMATION

Serious adverse events, including fatal events, have occurred with CALQUENCE, including serious and opportunistic infections, hemorrhage, cytopenias, second primary malignancies, cardiac arrhythmias, and hepatotoxicity, including drug-induced liver injury.

My name is Dr Elizabeth Brem and I am a medical oncologist at UCI Health.

I specialize in the diagnosis and treatment of B-cell malignancies, including chronic lymphocytic leukemia, or CLL. I see adult patients with CLL across various ages and disease states, with the majority of them being 50 years or older.

We know that CLL is a chronic disease that requires a long-term management, and more long-term follow up data can be valuable when making treatment decisions.

When it comes to informing my treatment decisions, factors including long-term follow-up data, a demonstrated safety profile, dosage and administration, and the patient's other medical problems play a crucial role in deciding on an appropriate treatment for my patients.

It's the data, including long-term follow-up data for CALQUENCE, that give me confidence in this treatment. And of course, in terms of its demonstrated safety profile, I have a high opinion of CALQUENCE based on both data from the clinical trials, as well as my personal experience.

My patients on CALQUENCE have done incredibly well and many have been progression-free for several years with some side effects that can be managed. This experience has reinforced my confidence in prescribing CALQUENCE.

Let's first look at the CALQUENCE data in first-line CLL.

ELEVATE-TN was a study of patients with previously untreated CLL for which there was a 90% PFS risk reduction with CALQUENCE plus obinutuzumab vs obinutuzumab plus chlorambucil and an 80% PFS risk reduction with CALQUENCE monotherapy vs obinutuzumab plus chlorambucil at 28.3-month median follow-up.

We also now have long-term follow-up data at 6 years. You can see here an estimated 6-year PFS of 78% in the CALQUENCE plus obinutuzumab arm and 62% in the CALQUENCE monotherapy arm.

Based on my experience, these data are consistent with what I have seen in my own patients on CALQUENCE.

I tend to prescribe BTK inhibitors in my high-risk patients with TP53 mutation or 17p deletion.

ELEVATE-TN included both CALQUENCE with obinutuzumab and CALQUENCE as a monotherapy. Which means that I have the option to use CALQUENCE with or without the monoclonal antibody, depending on my patient's treatment goal.

And as you can see, the rates of select cardiovascular AEs were low with CALQUENCE, both with and without obinutuzumab, which reinforces my confidence in prescribing CALQUENCE.

From the interim analysis for the most common ARs and events of clinical interest shown here, the safety and tolerability results of CALQUENCE at 6-year follow up were consistent.

When the ELEVATE-RR data was released, I genuinely appreciated AstraZeneca's bold decision to evaluate CALQUENCE in a head-to-head trial versus ibrutinib.

ELEVATE-RR is another study that helps in my treatment decision making for patients with relapse or refractory CLL.

ELEVATE-RR was the first Phase 3 study of a highly selective, next-generation BTKi vs ibrutinib and all of the patients enrolled in this study were high-risk patients. As you can see in the figure, the median PFS was 38.4 months for both arms at 41-month median follow-up.

Safety results seen in ELEVATE-RR were consistent with the ASCEND study in patients with relapsed/refractory CLL.

One of the reasons that I choose CALQUENCE for my patients is because of its established cardiovascular safety profile including the low rates of atrial fibrillation, hypertension, and Grade 3 or higher bleeding. This data is especially important to consider when it comes to my patients with cardiovascular comorbidities.

The approval of CALQUENCE was based on two Phase 3 studies: ELEVATE-TN for previously untreated CLL and ASCEND for relapsed/refractory CLL.

I touched on the ELEVATE-TN study earlier, but ASCEND was the first Phase 3 study of a BTKi vs IdR or BR in relapsed/refractory CLL. With a follow-up of nearly 4 years, you can see there is an estimated PFS of 62% in the CALQUENCE arm and 19% in the IdR/BR arm.

Consistent with the other studies, there were also low rates of atrial fibrillation, hypertension, and major hemorrhage. Together, the overall safety profile of CALQUENCE gives me assurance when prescribing CALQUENCE for my patients.

To learn more about CALQUENCE, take a moment to read through the study designs and additional clinical data, including the most common adverse events and events of clinical interest for ELEVATE-TN, ELEVATE-RR, and the ASCEND Phase 3 studies here.

With 6-year median follow-up data and demonstrated safety profile, I know what I can expect with CALQUENCE.

Regarding dosing and administration, for my patients with difficulty swallowing, I use CALQUENCE because of the small tablet size and its straightforward dosing regimen.

In my experience, for the majority of my patients, CALQUENCE is a tolerable treatment, where I can help manage some of their side effects.

Additionally, the MAIC, or matched-adjusted indirect comparison analysis, between CALQUENCE and Zanubrutinib may provide some additional context that may be helpful.

While a MAIC analysis has its limitations, it is an established method for indirectly comparing the relative treatment effect of different therapies.

Despite the limitations of conducting these types of analyses, they do help to see the differences, as the inclusion criteria differed between the studies.

By accounting for population differences between the studies, the MAIC analysis may help make informed decisions with the data currently available.

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To learn more about CALQUENCE, scan the QR code or visit calquencehcp.com

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 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%). 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.

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. 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% 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 16% of 2,055 patients exposed to CALQUENCE in clinical trials. 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. 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 (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

Chronic Lymphocytic Leukemia

The most common adverse reactions (≥30%) of any grade in patients with CLL in the ELEVATE-TN and ASCEND studies exposed to CALQUENCE (n=511) 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 in the ELEVATE-TN study exposed to CALQUENCE (n=357), 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% (69/178) of patients in the CALQUENCE plus obinutuzumab arm (n=178) and 32% (57/179) in the CALQUENCE monotherapy arm (n=179), 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 and CALQUENCE monotherapy arm, respectively. Adverse reactions led to discontinuation in 11% and 10% of patients, respectively. 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.

In patients with relapsed/refractory CLL in the ASCEND study exposed to CALQUENCE (n=154), 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, 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.

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