ASH News Daily 2012 - Monday, December 10, 2012 - (Page B-31)

A new opportunity FDA-approved Marqibo ® (vinCRIStine sulfate LIPOSOME injection) For the treatment of adult patients with Philadelphia chromosome–negative (Ph–) acute lymphoblastic leukemia (ALL) in second or greater relapse or whose disease has progressed following 2 or more antileukemia therapies. This indication is based on overall response rate. Clinical benefit such as improvement in overall survival has not been verified. • 15.4% (10/65) CR/CRi in patients who all received multiple prior therapies − 100% had previously received nonliposomal (standard) vincristine − 48% had undergone prior hematopoietic stem cell transplant (HSCT) − 51% had received 3 or more prior therapies − 45% were refractory to their immediate prior therapy − 85% had precursor B-cell ALL and 15% had precursor T-cell ALL − 100% were not eligible for immediate HSCT at enrollment − 34% did not receive asparaginase products • Marqibo® is sphingomyelin/cholesterol-based liposome– encapsulated vincristine − Plasma clearance of Marqibo® is slow, which contributes to a high plasma concentration in contrast to the rapid clearance of nonliposomal vincristine, which results in low plasma concentrations − Extended plasma circulation time contributes to a much higher AUC • The recommended dose of Marqibo® is 2.25 mg/m2 intravenously over 1 hour every 7 days. This dose delivers 2.25 mg/m2 of vincristine WARNING • For Intravenous Use Only—Fatal if Given by Other Routes • Death has occurred with intrathecal administration • Marqibo® (vinCRIStine sulfate LIPOSOME injection) has different dosage recommendations than vincristine sulfate injection. Verify drug name and dose prior to preparation and administration to avoid overdosage IMPORTANT SAFETY INFORMATION Contraindications • Marqibo® is contraindicated in patients with demyelinating conditions, including Charcot-Marie-Tooth syndrome; in patients with hypersensitivity to vincristine sulfate or any of the other components of Marqibo®; and for intrathecal administration Warnings and Precautions • Marqibo® is for intravenous use only—fatal if given by other routes. Intrathecal use is fatal. Extravasation causes tissue injury. If extravasation is suspected, discontinue infusion immediately and consider local treatment measures • Sensory and motor neuropathy are common and cumulative. Monitor patients for peripheral motor and sensory, central and autonomic neuropathy and reduce, interrupt, or discontinue dosing. Patients with preexisting severe neuropathy should be treated with Marqibo® only after careful risk-benefit assessment • Neutropenia, thrombocytopenia, or anemia may occur. Monitor blood counts prior to each dose. Consider dose modification or reduction as well as supportive care measures if Grade 3 or 4 myelosuppression develops • Anticipate, monitor for, and manage tumor lysis syndrome • A prophylactic bowel regimen should be instituted with Marqibo® to prevent constipation, bowel obstruction, and/or paralytic ileus • Severe fatigue can occur requiring dose delay, reduction, or discontinuation of Marqibo® • Fatal liver toxicity and elevated levels of aspartate aminotransferase have occurred. Monitor liver function and modify or interrupt dosing for hepatic toxicity • Marqibo® can cause fetal harm. Advise women of potential risk to fetus Adverse Events • The most commonly reported adverse reactions (incidence >30%) in clinical studies include constipation (57%), nausea (52%), pyrexia (43%), fatigue (41%), peripheral neuropathy (39%), febrile neutropenia (38%), diarrhea (37%), anemia (34%), decreased appetite (33%), and insomnia (32%) • A total of 75.9% of patients experienced serious adverse events (SAEs) during the studies. The most commonly reported SAEs included febrile neutropenia (20.5%), pyrexia (13.3%), hypotension (7.2%), respiratory distress (6.0%), and cardiac arrest (6.0%) • Twenty-eight percent of patients experienced adverse reactions leading to treatment discontinuation. The most common adverse reactions that caused treatment discontinuation were peripheral neuropathy (10%), leukemia-related (7%), and tumor lysis syndrome (2%) • Deaths occurred in 23% of patients in study 1. The nonleukemia-related causes of death were brain infarct (1), intracerebral hemorrhage (2), liver failure (1), multisystem organ failure (2), pneumonia and septic shock (3), respiratory failure (4), pulmonary hemorrhage (1), and sudden cardiac death (1) Drug Interactions • Marqibo® is expected to interact with drugs known to interact with nonliposomal vincristine sulfate, therefore the concomitant use of strong CYP3A inhibitors or the use of potent P-glycoprotein inhibitors or inducers should be avoided Use in Specific Populations • The safety and effectiveness of Marqibo® in pediatric patients have not been established • It is not known whether Marqibo® is excreted in human milk Please see Brief Summary of Prescribing Information, including Boxed Warning, on adjacent pages. Please see Prescribing Information at www.Marqibo.com. ©2012 Talon Therapeutics, Inc. Marqibo® is a registered trademark of Talon Therapeutics, Inc. All rights reserved. October 2012. Printed in the USA. MRQ002a www.TALONtx.com Delivering Opportunity

Table of Contents for the Digital Edition of ASH News Daily 2012 - Monday, December 10, 2012

ASH News Daily 2012 - Monday, December 10, 2012

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