ASH Clinical News May 2015 | Page 48

NOW WITH HEAD-TO-HEAD DATA vs rituximab + Clb In combination with chlorambucil (Clb) in first-line CLL1 START WITH GAZYVA CLL-11 Trial Design1,2: CLL-11 was a Phase III, open-label, multicenter, 3-arm, randomized, parallel-group comparative study in patients with previously untreated CD20-positive CLL and coexisting medical conditions or reduced renal function. Patients with creatinine clearance <30 mL/min or inadequate liver function were excluded. Patients were treated with chlorambucil control (Arm 1), GAZYVA in combination with chlorambucil (Arm 2), or rituximab in combination with chlorambucil (Arm 3). The safety and efficacy of GAZYVA was evaluated in a Stage 1 comparison of Arm 1 vs Arm 2 in 356 patients and a Stage 2 comparison of Arm 2 vs Arm 3 in 663 patients. The primary endpoint was progression-free survival, as evaluated by an independent review committee. Secondary endpoints included overall response rate, complete response rate, and response duration. IMPORTANT SAFETY INFORMATION Hepatitis B Virus Reactivation • Hepatitis B virus (HBV) reactivation, in some cases resulting in fulminant hepatitis, hepatic failure, and death, can occur in patients treated with anti-CD20 antibodies including GAZYVA. HBV reactivation has been reported in patients who are hepatitis B surface antigen (HBsAg) positive and in patients who are HBsAg negative but are hepatitis B core antibody (anti-HBc) positive. Reactivation has also occurred in patients who appear to have resolved hepatitis B infection (ie, HBsAg negative, anti-HBc positive, and hepatitis B surface antibody [anti-HBs] positive) • HBV reactivation is defined as an abrupt increase in HBV replication manifesting as a rapid increase in serum HBV DNA level, or detection of HBsAg in a person who was previously HBsAg negative and anti-HBc positive. Reactivation of HBV replication is often followed by hepatitis, ie, increase in transaminase levels and, in severe cases, increase in bilirubin levels, liver failure, and death • Screen all patients for HBV infection by measuring HBsAg and anti-HBc before initiating treatment with GAZYVA. For patients who show evidence of hepatitis B infection (HBsAg positive [regardless of antibody status] or HBsAg negative but antiHBc positive), consult physicians with expertise in managing hepatitis B regarding monitoring and consideration for HBV antiviral therapy • Monitor patients with evidence of current or prior HBV infection for clinical and laboratory signs of hepatitis or HBV reactivation during and for several months following treatment with GAZYVA • In patients who develop reactivation of HBV while receiving GAZYVA, immediately discontinue GAZYVA and any concomitant chemotherapy and institute appropriate treatment. Resumption of GAZYVA in patients whose HBV reactivation resolves should be discussed with physicians with expertise in managing hepatitis B. Insufficient data exist regarding the safety of resuming GAZYVA in patients who develop HBV reactivation Progressive Multifocal Leukoencephalopathy (PML) • JC virus infection resulting in PML, which can be fatal, was observed in patients treated with GAZYVA. Consider the diagnosis of PML in any patient presenting with new onset or changes to preexisting neurologic manifestations. Evaluation of PML includes, but is not limited to, consultation with a neurologist, brain MRI, and lumbar puncture. Discontinue GAZYVA therapy and consider discontinuation or reduction of any concomitant chemotherapy or immunosuppressive therapy in patients who develop PML