Calquence

Mantle Cell Lymphoma

Calquence is used to treat adults with mantle cell lymphoma (MCL), a fast-growing type of non-Hodgkin lymphoma. It is prescribed in the following situations:

• For patients who have already received at least one prior treatment for their cancer.
• In combination with the medications bendamustine and rituximab for patients who have not been treated previously for MCL.

Chronic Lymphocytic Leukemia and Small Lymphocytic Lymphoma

Calquence is also used to treat adults with:

• Chronic Lymphocytic Leukemia (CLL): A type of cancer that begins in the white blood cells in the bone marrow.
• Small Lymphocytic Lymphoma (SLL): A cancer that primarily affects the lymph nodes and is closely related to CLL.

This medication belongs to a class of drugs called kinase inhibitors. It works by blocking specific proteins that help cancer cells grow and spread.

Mechanism of Action

Calquence belongs to a class of medications called kinase inhibitors. It works by targeting and blocking a protein in the body known as Bruton's tyrosine kinase (BTK).

BTK is a signaling protein found in B-cells, which are a type of white blood cell. In certain types of blood and lymph node cancers, BTK sends signals that cause these B-cells to grow, multiply, and spread uncontrollably. By inhibiting this protein, Calquence helps to:

• Interrupt the signals that allow cancer cells to survive.
• Prevent the cancer cells from multiplying.
• Slow the progression of the disease.

Because it specifically targets the BTK protein, Calquence is considered a targeted therapy. This means it is designed to interfere with specific molecules involved in the growth of cancer cells rather than affecting all rapidly dividing cells in the body.

Common Side Effects

The most frequently reported side effects associated with Calquence include:

• Headache
• Diarrhea
• Muscle and joint pain
• Fatigue or tiredness
• Bruising
• Nausea
• Rash
• Abdominal pain
• Constipation

Serious Side Effects

While less common, Calquence can cause serious health problems that may require medical intervention:

• Serious Infections: The medication can weaken the immune system, increasing the risk of severe bacterial, viral, or fungal infections.
• Bleeding: Major bleeding episodes can occur. The risk may be higher for those taking blood thinners or antiplatelet medications.
• Heart Rhythm Issues: Some people experience heart rhythm disturbances, such as atrial fibrillation or atrial flutter. Symptoms may include palpitations, dizziness, or chest discomfort.
• Low Blood Cell Counts: Calquence can cause a significant drop in white blood cells, red blood cells, and platelets, which can increase the risk of infection, anemia, or bleeding.
• New Cancers: There is a risk of developing other types of cancer, particularly skin cancers, while taking this treatment.

Bleeding Risks

Calquence can cause serious and sometimes fatal bleeding. The risk may be increased in people who are also taking blood thinners or antiplatelet drugs. Medical professionals may recommend stopping the medication temporarily before and after planned surgeries.

Infections

Serious bacterial, viral, and fungal infections have been reported, some of which have been fatal. Monitoring for symptoms like fever, chills, or flu-like symptoms is necessary. There is also a risk of hepatitis B virus reactivation in people who have previously had the virus.

Heart Rhythm Issues

Some people taking this medication develop heart rhythm problems, such as atrial fibrillation or atrial flutter. This risk is higher for those with existing heart conditions, high blood pressure, or diabetes.

Blood Count Changes

Treatment may lead to low levels of white blood cells (neutropenia), red blood cells (anemia), or platelets (thrombocytopenia). Healthcare providers typically perform regular blood tests to monitor these levels.

New Cancers

There is an increased risk of developing other types of cancer, particularly skin cancers. It is recommended to use sun protection and have regular skin checks.

Tumor Lysis Syndrome

Rapid breakdown of cancer cells can lead to tumor lysis syndrome, which can cause kidney failure or abnormal heart rhythms. This is more common in patients with a high number of cancer cells before treatment.

Pregnancy and Fetal Harm

Based on its mechanism of action, Calquence may cause harm to a developing fetus. Effective contraception is recommended for those of reproductive potential during treatment and for a specific time after the final dose.

Pregnancy

Calquence can cause harm to a fetus if taken during pregnancy. Based on findings from animal studies, the medication may lead to decreased fetal weight and other developmental issues. Healthcare providers typically advise the following:

• Pregnancy testing: A pregnancy test is often recommended for individuals of reproductive potential before starting treatment to ensure they are not pregnant.
• Contraception: Effective birth control should be used during treatment and for at least one week after the last dose of Calquence.
• Communication: If you become pregnant or think you might be pregnant while taking this medication, contact your healthcare provider to discuss the potential risks to the fetus.

Breastfeeding

It is not known whether Calquence passes into human breast milk or how it might affect a nursing infant. Because of the potential for serious adverse reactions in a breastfed child, it is recommended to avoid breastfeeding during treatment and for at least two weeks after the final dose.

Dosage Forms

Calquence is available in the following oral formulations:

• Capsules
• Tablets

The tablet formulation was developed to allow for administration with or without food and to be compatible with certain medications that reduce stomach acid. Both the capsules and tablets should be swallowed whole and not crushed, chewed, or dissolved.

FDA Approval History

Calquence was first approved by the U.S. Food and Drug Administration (FDA) in October 2017. The initial approval was granted under the accelerated approval pathway for the treatment of adults with mantle cell lymphoma (MCL) who had received at least one prior therapy. Continued approval for this indication may be contingent upon verification of clinical benefit in confirmatory trials.

In November 2019, the FDA expanded the approval of Calquence to include the treatment of adults with chronic lymphocytic leukemia (CLL) or small lymphocytic lymphoma (SLL).

Recent Regulatory Updates

In 2024, the FDA approved Calquence in combination with bendamustine and rituximab for the treatment of adults with previously untreated mantle cell lymphoma. This expanded the drug's use to include first-line treatment for this specific condition.

Current Approved Indications

Calquence is currently FDA-approved for the following uses:

• Chronic Lymphocytic Leukemia (CLL): For the treatment of adult patients.
• Small Lymphocytic Lymphoma (SLL): For the treatment of adult patients.
• Mantle Cell Lymphoma (MCL): For adult patients who have received at least one prior therapy, or in combination with other medications for previously untreated patients.

Safety and Monitoring

There are currently no boxed warnings or Risk Evaluation and Mitigation Strategy (REMS) programs required for Calquence. The medication is available by prescription only and its safety continues to be monitored through post-marketing surveillance and clinical trial data.

Estimated Retail Price

Calquence is a high-cost specialty medication. The retail price for a 30-day supply, which typically consists of 60 capsules or tablets (100 mg), is approximately $16,500 to $17,000. Most patients do not pay this full amount out of pocket, as costs are often offset by insurance or assistance programs.

Factors Influencing Cost

• Insurance and Medicare: Most commercial insurance plans and Medicare Part D provide coverage for Calquence. However, because it is a specialty drug, it is often placed on a higher formulary tier, which may require a significant co-pay or coinsurance payment.
• Generic Availability: There is currently no generic version of acalabrutinib available. Brand-name medications typically remain at a higher price point until generic alternatives are approved and released.
• Pharmacy Selection: Prices can vary between specialty pharmacies. Some insurance providers may require the use of a specific specialty pharmacy to manage the distribution of this medication.

Financial Assistance Programs

The manufacturer of Calquence offers support programs to help manage costs for eligible patients. These may include co-pay cards for those with commercial insurance to reduce out-of-pocket expenses, or patient assistance programs for individuals who are uninsured or underinsured and meet specific income requirements.