Acalabrutinib

Approved Uses

Acalabrutinib is used to treat the following conditions:

• Chronic Lymphocytic Leukemia (CLL): A slow-growing cancer that affects a type of white blood cell called B-lymphocytes.
• Small Lymphocytic Lymphoma (SLL): A cancer that is closely related to CLL but primarily affects the lymph nodes.
• Mantle Cell Lymphoma (MCL): A fast-growing form of non-Hodgkin lymphoma.

For mantle cell lymphoma, this medication is typically prescribed for adults who have already received at least one other treatment for their cancer. It may also be used as an initial treatment in combination with other medications for patients who have not been treated previously.

Acalabrutinib belongs to a class of drugs known as kinase inhibitors. It works by blocking a specific protein that helps cancer cells grow and divide.

Mechanism of Action

Acalabrutinib is a type of targeted therapy known as a Bruton tyrosine kinase (BTK) inhibitor. It works by interfering with the signals that allow certain cancer cells to grow and multiply.

In the body, BTK is a protein that plays a key role in the development and survival of B-cells, which are a type of white blood cell. In some blood cancers, the B-cells become abnormal and multiply uncontrollably because the BTK protein is constantly sending growth signals.

Acalabrutinib works by binding to the BTK protein and blocking its activity. By shutting down these signals, the medication helps to:

• Inhibit cell growth: It prevents the cancerous B-cells from dividing and increasing in number.
• Reduce cancer spread: It makes it harder for cancer cells to migrate and survive in different parts of the body.
• Induce cell death: Without the necessary survival signals from BTK, the cancerous cells may eventually die.

Common Side Effects

Many people taking acalabrutinib experience mild to moderate side effects. These may include:

• Headache
• Diarrhea
• Muscle or joint pain
• Feeling tired or weak
• Bruising or small red spots on the skin
• Nausea
• Rash
• Constipation
• Dizziness
• Symptoms of a cold or upper respiratory infection

Serious Side Effects

Some side effects can be serious and require immediate medical attention. Contact a healthcare provider right away if you experience:

• Bleeding: Signs include blood in the stool or urine, coughing up blood, or unusual bruising.
• Infections: Fever, chills, or other signs of infection.
• Heart rhythm problems: Feeling like your heart is racing, skipping beats, or fluttering, often accompanied by shortness of breath or chest discomfort.
• Low blood cell counts: This may cause an increased risk of infection, bleeding, or fatigue.
• New cancers: Some people may develop new types of cancer, such as skin cancer, while taking this medication.

Serious Bleeding

Acalabrutinib can cause serious and sometimes fatal bleeding events (hemorrhage). The risk of bleeding may increase if the medication is taken with blood thinners, such as anticoagulants or antiplatelet agents. Healthcare providers may advise pausing treatment for several days before and after a planned surgical procedure to reduce this risk.

Infections

Serious bacterial, viral, or fungal infections, including opportunistic infections and pneumonia, have occurred in patients taking this medication. Some infections can be life-threatening or fatal. Healthcare providers monitor for signs of infection and may prescribe preventative medications for certain types of infections during treatment.

Heart Rhythm Problems

Atrial fibrillation and atrial flutter (irregular or fast heartbeats) have been reported. This risk may be higher for individuals with a history of heart disease, high blood pressure, or diabetes. Monitoring for symptoms such as palpitations, chest discomfort, dizziness, or fainting is typically part of the treatment plan.

Low Blood Cell Counts

Treatment can lead to significant decreases in blood cell counts, which may include:

• Neutropenia: A decrease in white blood cells that fight infection.
• Anemia: A decrease in red blood cells that carry oxygen.
• Thrombocytopenia: A decrease in platelets, which can lead to easy bruising or bleeding.

Regular blood tests are necessary to monitor these levels throughout the course of therapy.

Second Primary Malignancies

There is an increased risk of developing other types of cancer, most commonly skin cancers. Protection from sun exposure and regular skin checks are often recommended for patients taking this medication.

Other Precautions

• Hepatitis B Reactivation: In people who have previously had hepatitis B, the virus can become active again. Testing for hepatitis B is usually performed before starting treatment.
• Tumor Lysis Syndrome: This condition occurs when cancer cells break down quickly, releasing their contents into the blood. This can cause kidney damage and other serious issues.
• Pregnancy and Breastfeeding: Acalabrutinib may cause harm to an unborn baby. Effective birth control is generally recommended during treatment and for a period after the final dose. Breastfeeding is typically not recommended during treatment and for two weeks after the last dose.

Pregnancy

There are no adequate studies on the use of acalabrutinib in pregnant women to determine drug-associated risks. However, based on findings from animal studies, this medication may cause harm to a developing fetus when administered during pregnancy. Healthcare providers typically discuss the potential risks to the fetus if the medication is used during pregnancy.

Key considerations for individuals of reproductive potential include:

• Pregnancy Testing: Healthcare providers may verify pregnancy status in females of reproductive potential before starting treatment.
• Contraception: Individuals who can become pregnant are usually advised to use effective birth control during treatment and for at least one week after the final dose of acalabrutinib.

Breastfeeding

It is not known whether acalabrutinib or its metabolites are present in human breast milk. There is also no information regarding the effects of the drug on a breastfed child or on milk production. Because of the potential for serious adverse reactions in a nursing infant, healthcare providers generally advise women not to breastfeed during treatment and for at least two weeks after the last dose.

Available Forms

Acalabrutinib is taken by mouth. It is currently available in the following dosage forms:

• Capsules
• Tablets

Your healthcare provider will determine the appropriate form and strength for your specific treatment plan.

FDA Approval History

Acalabrutinib received its initial FDA approval in October 2017. It was originally authorized for the treatment of adults with mantle cell lymphoma who had already received at least one prior therapy. Since its initial approval, the FDA has expanded the authorized uses of the medication to include additional conditions and treatment combinations.

Approved Indications

Acalabrutinib is currently FDA-approved for the following indications:

• Mantle Cell Lymphoma (MCL): It is approved for adults who have received at least one prior therapy. In 2024, the FDA also approved its use in combination with bendamustine and rituximab for adults with previously untreated MCL.
• Chronic Lymphocytic Leukemia (CLL): It is approved for the treatment of adults with CLL, including those who have not been treated before and those whose cancer has returned or did not respond to previous treatment.
• Small Lymphocytic Lymphoma (SLL): It is approved for the treatment of adults with SLL, including both previously untreated and relapsed or refractory cases.

Regulatory Status

Acalabrutinib is available only by prescription. There are currently no boxed warnings or Risk Evaluation and Mitigation Strategy (REMS) requirements associated with this medication. During its development and review process, the FDA granted acalabrutinib several special designations, including Breakthrough Therapy and Orphan Drug status, which are intended to facilitate the development of treatments for serious or rare conditions.

Factors Influencing Cost

Several factors determine the final price you may pay for acalabrutinib:

• Insurance Coverage: Most private insurance plans and Medicare Part D provide coverage for acalabrutinib. However, the amount you pay out-of-pocket will depend on your plan's specific deductible, copayment, or coinsurance requirements.
• Specialty Pharmacy Requirements: Acalabrutinib is often classified as a specialty medication. It may not be available at all local pharmacies and may need to be ordered through a specialty pharmacy, which can affect billing and delivery.
• Dosage and Treatment Length: The total cost is influenced by the strength of the medication and how long your healthcare provider determines you need to remain on the therapy.

Insurance and Prior Authorization

Because acalabrutinib is a high-cost specialty drug, many insurance companies require a process called prior authorization. This means your doctor must provide documentation to your insurance provider to confirm that the medication is medically necessary before the plan will agree to cover the cost.

Financial Assistance Options

For patients who have difficulty affording their medication, there are several potential avenues for financial support:

• Manufacturer Assistance: The drug manufacturer may offer patient assistance programs or copay cards for eligible patients with commercial insurance to help lower out-of-pocket expenses.
• Non-Profit Organizations: Some independent foundations provide grants or financial aid to help patients cover the costs of cancer treatments and related expenses.
• Government Programs: Patients with limited income may qualify for Extra Help through Medicare or other state-funded programs to assist with prescription drug costs.

It is advisable to consult with your healthcare team, a social worker, or a specialty pharmacist to identify the most appropriate financial resources for your situation.