ASH Clinical News Focus on Myeloid Malignancies

#1 PRESCRIBED ORAL CLL THERAPY.* MORE THAN 20,000 PATIENTS TREATED SINCE APPROVAL 1 † MAKE IMBRUVICA® YOUR FIRST STEP Approved in frontline CLL with or without 17p deletion 2 CLL SLL IMBRUVICA® is a once-daily oral therapy indicated for: • Chronic lymphocytic leukemia (CLL)/small lymphocytic lymphoma (SLL) 2 • CLL/SLL with 17p deletion 2 IMPORTANT SAFETY INFORMATION WARNINGS AND PRECAUTIONS Hemorrhage - Fatal bleeding events have occurred in patients treated with IMBRUVICA ® . Grade 3 or higher bleeding events (intracranial hemorrhage [including subdural hematoma], gastrointestinal bleeding, hematuria, and post-procedural hemorrhage) have occurred in up to 6% of patients. Bleeding events of any grade, including bruising and petechiae, occurred in approximately half of patients treated with IMBRUVICA ® . The mechanism for the bleeding events is not well understood. IMBRUVICA ® may increase the risk of hemorrhage in patients receiving antiplatelet or anticoagulant therapies and patients should be monitored for signs of bleeding. Consider the beneﬁ t-risk of withholding IMBRUVICA ® for at least 3 to 7 days pre- and postsurgery depending upon the type of surgery and the risk of bleeding. Infections - Fatal and nonfatal infections have occurred with IMBRUVICA ® therapy. Grade 3 or greater infections occurred in 14% to 29% of patients. Cases of progressive multifocal leukoencephalopathy (PML) and Pneumocystis jirovecii pneumonia (PJP) have occurred in patients treated with IMBRUVICA ® . Evaluate patients for fever and infections and treat appropriately. Cytopenias - Treatment-emergent Grade 3 or 4 cytopenias including neutropenia (range, 13% to 29%), thrombocytopenia (range, 5% to 17%), and anemia (range, 0% to 13%) based on laboratory measurements occurred in patients treated with single agent IMBRUVICA ® . Monitor complete blood counts monthly. Atrial Fibrillation - Atrial ﬁ brillation and atrial ﬂ utter (range, 6% to 9%) have occurred in patients treated with IMBRUVICA ® , particularly in patients with cardiac risk factors, hypertension, acute infections, and a previous history of atrial ﬁ brillation. Periodically monitor patients clinically for atrial ﬁ brillation. Patients who develop arrhythmic symptoms (eg, palpitations, lightheadedness) or new-onset dyspnea should have an ECG performed. Atrial ﬁ brillation should be managed appropriately and if it persists, consider the risks and beneﬁ ts of IMBRUVICA ® treatment and follow dose modiﬁ cation guidelines. Hypertension - Hypertension (range, 6% to 17%) has occurred in patients treated with IMBRUVICA ® with a median time to onset of 4.6 months (range, 0.03 to 22 months). Monitor patients for new-onset hypertension or hypertension that is not adequately controlled after starting IMBRUVICA ® . Adjust existing antihypertensive medications and/or initiate antihypertensive treatment as appropriate. Second Primary Malignancies - Other malignancies (range, 3% to 16%) including non-skin carcinomas (range, 1% to 4%) have occurred in patients treated with IMBRUVICA ® . The most frequent second primary malignancy was non-melanoma skin cancer (range, 2% to 13%). Tumor Lysis Syndrome - Tumor lysis syndrome has been infrequently reported with IMBRUVICA ® therapy. Assess the baseline risk (eg, high tumor burden) and take appropriate precautions. Monitor patients closely and treat as appropriate. Embryo-Fetal Toxicity - Based on ﬁ ndings in animals, IMBRUVICA ® can cause fetal harm when administered to a pregnant woman. Advise women to avoid becoming pregnant while taking IMBRUVICA ® and for 1 month after cessation of therapy. If this drug is used during pregnancy or if the patient becomes pregnant while taking this

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