ASH Clinical News December 2014

IMPORTANT SAFETY INFORMATION (CONT’D) Infusion Reactions (cont’d) • For patients with any Grade 4 infusion reactions, including but not limited to anaphylaxis, acute life-threatening respiratory symptoms, or other life-threatening infusion reaction: Stop the GAZYVA infusion. Permanently discontinue GAZYVA therapy • For patients with Grade 1, 2, or 3 infusion reactions: Interrupt GAZYVA for Grade 3 reactions until resolution of symptoms. Interrupt or reduce the rate of the infusion for Grade 1 or 2 reactions and manage symptoms For patients with preexisting cardiac or pulmonary conditions, • monitor more frequently throughout the infusion and the postinfusion period since they may be at greater risk of experiencing more severe reactions. Hypotension may occur as part of the GAZYVA infusion reaction. Consider withholding antihypertensive treatments for 12 hours prior to and during each GAZYVA infusion, and for the first hour after administration until blood pressure is stable. For patients at increased risk of hypertensive crisis, consider the benefits versus the risks of withholding their hypertensive medication Tumor Lysis Syndrome (TLS) • Acute renal failure, hyperkalemia, hypocalcemia, hyperuricemia, and/or hyperphosphatemia from TLS can occur within 12-24 hours after the first infusion. Patients with high tumor burden and/or high circulating lymphocyte count (>25 x 109/L) are at greater risk for TLS and should receive appropriate tumor lysis prophylaxis with anti-hyperuricemics (e.g., allopurinol) and hydration beginning 12-24 hours prior to the infusion of GAZYVA. For treatment of TLS, correct electrolyte abnormalities, monitor renal function and fluid balance, and administer supportive care, including dialysis, as indicated Infections • Serious bacterial, fungal, and new or reactivated viral infections can occur during and following GAZYVA therapy. Do not administer GAZYVA to patients with an active infection. Patients with a history of recurring or chronic infections may be at increa sed risk of infection Neutropenia • GAZYVA, in combination with chlorambucil, caused Grade 3 or 4 neutropenia in 34% of patients. Patients with Grade 3 to 4 neutropenia should be monitored frequently with regular laboratory tests until resolution. Anticipate, evaluate, and treat any symptoms or signs of developing infection • Neutropenia can also be of late onset (occurring more than 28 days after completion of treatment) and/or prolonged (lasting longer than 28 days) • Patients with neutropenia are strongly recommended to receive antimicrobial prophylaxis throughout the treatment period. Antiviral and antifungal prophylaxis should be considered Thrombocytopenia • GAZYVA, in combination with chlorambucil, caused Grade 3 or 4 thrombocytopenia in 11% of patients in the trial. In 5% of patients, GAZYVA caused acute thrombocytopenia occurring within 24 hours after the GAZYVA infusion. Fatal hemorrhagic events during Cycle 1 have also been reported. Monitor all patients frequently for thrombocytopenia and hemorrhagic events, especially during the first cycle. In patients with Grade 3 or 4 thrombocytopenia, monitor platelet counts more frequently until resolution and consider subsequent dose delays of GAZYVA and chlorambucil or dose reductions of chlorambucil. Transfusion of blood products (ie, platelet transfusion) may be necessary. Consider withholding concomitant medications which may increase bleeding risk (platelet inhibitors, anticoagulants), especially during the first cycle Immunization • The safety and efficacy of immunization with live or attenuated viral vaccines during or following GAZYVA therapy has not been studied. Immunization with live virus vaccines is not recommended during treatment and until B-cell recovery Pregnancy: Category C • Women of childbearing potential should use effective contraception while receiving GAZYVA and for 12 months following treatment. GAZYVA should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus Geriatric Use • Two hundred and forty previously untreated CLL patients received GAZYVA in combination with chlorambucil. Of the 109 patients ≥75 years of age, 49 (45%) experienced serious adverse events and 5 (5%) experienced adverse events leading to death. For 131 patients <75 years of age, 39 (30%) experienced a serious adverse event and 3 (2%) experienced an adverse event leading to death. Similar rates were observed in the comparator arm Additional Important Safety Information • The most common adverse reactions (incidence ≥10%) were: infusion reactions (69%), neutropenia (40%), thrombocytopenia (15%), anemia (12%), pyrexia (10%), cough (10%), and musculoskeletal disorders (17%) • Grade 3/4 adverse reactions were: infusion reactions (21%), neutropenia (34%), thrombocytopenia (11%), anemia (4%), leukopenia (5%), and pyrexia (<1%) You are encouraged to report side effects to Genentech and the FDA. You may contact Genentech by calling 1-888-835-2555. You may contact the FDA by visiting www.fda.gov/medwatch, or calling 1-800-FDA-1088. References: 1. GAZYVA full Prescribing Information. South San Francisco, CA: Genentech USA, Inc.; June 2014. 2. Referenced with permission from the NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines®) for Non-Hodgkin’s Lymphomas V.3.2014. © National Comprehensive Cancer Network, Inc. 2014. All rights reserved. Accessed July 25, 2014. To view the most recent and complete version of the guideline, go online to www.nccn.org. NATIONAL COMPREHENSIVE CANCER NETWORK®, NCCN®, NCCN GUIDELINES®, and all other NCCN Content are trademarks owned by the National Comprehensive Cancer Network, Inc. Please see the following pages for additional Important Safety Information and brief summary of full Prescribing Information, including Boxed WARNINGS. Visit GAZYVA.com for more information © 2014 Genentech USA, Inc. All rights reserved. GAZ0002666300 Printed in USA. November 2014

ASH Clinical News December 2014 | Page 52