Acalabrutinib

Acalabrutinib is an orally administered targeted anticancer medicine belonging to the Bruton tyrosine kinase inhibitor class. It selectively and irreversibly inhibits Bruton tyrosine kinase, an enzyme involved in B-cell receptor signaling that supports the growth, survival and migration of abnormal B lymphocytes. By blocking this pathway, acalabrutinib reduces signaling that contributes to the proliferation and persistence of malignant B cells. It is used in adults with chronic lymphocytic leukemia or small lymphocytic lymphoma and in selected settings of mantle cell lymphoma, either alone or in combination with other anticancer medicines. Depending on the regulatory jurisdiction and treatment setting, it may be used as monotherapy or together with obinutuzumab, venetoclax, bendamustine and rituximab. Acalabrutinib is administered orally, generally at 100 mg approximately every 12 hours. Treatment is usually continued until disease progression or unacceptable toxicity, although combination regimens may have defined treatment durations for their accompanying medicines. Important clinical monitoring includes complete blood counts, signs of infection or bleeding, cardiac rhythm, liver function and potential drug interactions because acalabrutinib can cause clinically significant hematologic, cardiovascular, hepatic and infectious complications.

Acalabrutinib was developed as a selective second-generation Bruton tyrosine kinase inhibitor intended to provide effective B-cell receptor pathway inhibition while maintaining a more selective pharmacologic profile than earlier BTK inhibitors. The U.S. Food and Drug Administration granted accelerated approval in October 2017 for adults with mantle cell lymphoma who had received at least one prior therapy. FDA subsequently approved acalabrutinib for chronic lymphocytic leukemia and small lymphocytic lymphoma in November 2019. In January 2025, FDA converted the previously treated MCL indication to traditional approval and approved acalabrutinib in combination with bendamustine and rituximab for previously untreated MCL in adults who are ineligible for autologous hematopoietic stem cell transplantation. In February 2026, FDA approved acalabrutinib in combination with venetoclax for adults with CLL or SLL based on the AMPLIFY study. In the European Union, Calquence received marketing authorisation on 5 November 2020, with subsequent extensions covering additional CLL and MCL treatment settings, including combinations with venetoclax and other anticancer medicines. Indian CDSCO records document approval of acalabrutinib capsules or tablets and subsequent regulatory consideration of additional MCL indications. Key clinical development programmes include ACE-CL-001, ELEVATE-TN, ASCEND, ELEVATE-RR, ECHO and AMPLIFY.

Acalabrutinib is used for adults with chronic lymphocytic leukemia or small lymphocytic lymphoma and for selected adults with mantle cell lymphoma. In CLL or SLL, it may be used as monotherapy or in combination with other medicines depending on the approved regimen and jurisdiction. Current regulatory indications include combination treatment with obinutuzumab in previously untreated CLL and, in applicable settings, combination treatment with venetoclax with or without obinutuzumab. In the United States, the 2026 approval also includes acalabrutinib plus venetoclax for adults with CLL or SLL. For mantle cell lymphoma, acalabrutinib is used as monotherapy in adults who have received at least one prior therapy and is also approved in combination with bendamustine and rituximab for previously untreated adults who are ineligible for autologous hematopoietic stem cell transplantation. Treatment selection should consider disease subtype, previous therapy, transplant eligibility, genetic and clinical risk factors, concomitant medicines and the regulatory indication applicable to the specific product and jurisdiction.

Acalabrutinib is administered orally at a recommended dose of 100 mg approximately every 12 hours for adults with MCL, CLL or SLL under the current U.S. prescribing information. The tablet should be swallowed whole with water and may be taken with or without food; it should not be chewed, crushed, dissolved or cut. In combination with bendamustine and rituximab for previously untreated MCL, acalabrutinib is continued at 100 mg approximately every 12 hours while bendamustine and rituximab are administered according to their specified treatment schedule. In combination with obinutuzumab for previously untreated CLL or SLL, acalabrutinib is generally started from the first treatment cycle while obinutuzumab is introduced from a later cycle according to the approved regimen. Combination with venetoclax may involve a defined treatment duration depending on the regulatory regimen and accompanying therapy. For disease treated with acalabrutinib monotherapy, treatment is generally continued until disease progression or unacceptable toxicity. Dose interruption or reduction may be required for significant adverse reactions or clinically important drug interactions.

Common side effects of acalabrutinib include diarrhea, upper respiratory tract infection, headache, musculoskeletal pain, lower respiratory tract infection and fatigue. Other adverse effects may include nausea, bruising, cough, joint pain, constipation, dizziness, rash and changes in blood counts. Laboratory abnormalities can include reductions in neutrophils, lymphocytes, platelets and hemoglobin. When acalabrutinib is combined with bendamustine and rituximab or other anticancer medicines, the overall adverse-effect profile may include additional toxicities associated with the combination. The frequency and severity of adverse effects vary according to the disease, treatment combination, duration of therapy and individual patient characteristics. Many non-serious adverse reactions can be managed through supportive treatment, clinical monitoring, temporary interruption or dose modification under medical supervision.

Important serious risks associated with acalabrutinib include serious and opportunistic infections, hemorrhage, cytopenias, second primary malignancies, cardiac arrhythmias and hepatotoxicity including drug-induced liver injury. Significant bleeding can occur and may be more clinically important in patients receiving anticoagulant or antiplatelet medicines. Acalabrutinib can reduce blood-cell counts, increasing the risk of infection, anemia or bleeding, and regular complete blood-count monitoring is required. Cardiac arrhythmias, including atrial fibrillation or atrial flutter, have been reported and require clinical assessment when palpitations, dizziness, fainting or shortness of breath develop. Liver injury can occur and may require treatment interruption or discontinuation depending on severity. Patients should also be monitored for new cancers, particularly skin cancers, and advised regarding appropriate sun protection. Acalabrutinib may cause fetal harm, and appropriate pregnancy precautions are required.

Before starting treatment, healthcare professionals should assess the patient's blood counts, infection history, bleeding risk, cardiovascular history, liver function and current medicines. Complete blood counts should be monitored regularly, and patients should be assessed promptly for fever, persistent infections, unusual bruising or bleeding. Acalabrutinib is metabolized mainly through CYP3A pathways, making interactions with CYP3A inhibitors and inducers clinically important. Strong CYP3A inhibitors should generally be avoided, while moderate CYP3A inhibitors may require dose reduction. Strong CYP3A inducers should generally be avoided; if unavoidable, an increased acalabrutinib dose may be required according to prescribing information. Acid-reducing medicines can also affect exposure depending on the formulation, so medication review should include proton-pump inhibitors, H2-receptor antagonists and antacids. Anticoagulants and antiplatelet medicines require particular attention because of the potential for increased bleeding risk. Live vaccines should generally be avoided unless specifically recommended by a healthcare professional. Severe hepatic impairment is a reason to avoid acalabrutinib under the current U.S. prescribing information.

Prescribers should confirm the hematologic diagnosis, disease stage, previous treatment, transplant eligibility and applicable regulatory indication before initiating acalabrutinib. Baseline assessment should include complete blood count, liver function, infection history, cardiovascular history and a detailed review of concomitant medicines. Patients should be counselled to report fever, persistent infection, unusual bruising, bleeding, palpitations, dizziness, fainting, shortness of breath, jaundice or other new symptoms promptly. Pharmacists should verify the twice-daily dosing schedule, tablet or capsule formulation, administration instructions and potential CYP3A interactions before dispensing. Particular attention should be given to anticoagulants, antiplatelet medicines and acid-reducing therapies. For combination regimens, the timing and duration of accompanying medicines such as obinutuzumab, bendamustine, rituximab or venetoclax should be checked carefully. Regular communication between hematology, oncology, pharmacy and laboratory teams helps identify infections, cytopenias, bleeding, cardiac events and liver toxicity early and supports appropriate treatment interruption or dose modification.