Hemorrhage: Serious hemorrhagic events, including fatal events, have occurred in the combined safety database of 612 patients with hematologic malignancies treated with Acalabrutinib monotherapy. Grade 3 or higher bleeding events, including gastrointestinal, intracranial, and epistaxis have been reported in 2% of patients. Overall, bleeding events including bruising and petechiae of any grade occurred in approximately 50% of patients with hematological malignancies. The mechanism for the bleeding events is not well understood. Acalabrutinib may further increase the risk of hemorrhage in patients receiving antiplatelet or anticoagulant therapies and patients should be monitored for signs of bleeding. Consider the benefit-risk of withholding Acalabrutinib for 3-7 days pre- and post-surgery depending upon the type of surgery and the risk of bleeding.Infection: Serious infections (bacterial, viral or fungal), including fatal events and opportunistic infections have occurred in the combined safety database of 612 patients with hematologic malignancies treated with Acalabrutinib monotherapy. Consider prophylaxis in patients who are at increased risk for opportunistic infections. Grade 3 or higher infections occurred in 18% of these patients. The most frequently reported Grade 3 or 4 infection was pneumonia. Infections due to hepatitis B virus (HBV) reactivation and progressive multifocaln leukoencephalopathy (PML) have occurred. Monitor patients for signs and symptoms of infection and treat as medically appropriate. Cytopenias: In the combined safety database of 612 patients with hematologic malignancies, patients treated with Acalabrutinib monotherapy experienced Grade 3 or 4 cytopenias, including neutropenia (23%), anemia (11%) and thrombocytopenia (8%) based on laboratory measurements. In the Acalabrutinib clinical Trial LY-004, patients’ complete blood counts were assessed monthly during treatment.Second Primary Malignancies: Second primary malignancies, including non-skin carcinomas, have occurred in 11% of patients with hematologic malignancies treated with Acalabrutinib monotherapy in the combined safety database of 612 patients. The most frequent second primary malignancy was skin cancer, reported in 7% of patients. Advise protection from sun exposure.Atrial Fibrillation and Flutter: In the combined safety database of 612 patients with hematologic malignancies treated with Acalabrutinib monotherapy, atrial fibrillation and atrial flutter of any grade occurred in 3% of patients, and Grade 3 in 1% of patients. Monitor for atrial fibrillation and atrial flutter and manage as appropriate.
