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| |  Infection-Related Deaths Reported With Alemtuzumab, Warns Health Canada OTTAWA, Ontario -- November 21, 2008 -- Bayer HealthCare and Genzyme, in collaboration with Health Canada, are informing healthcare professionals regarding infection-related deaths that have been reported with the use of alemtuzumab as consolidation therapy following combination treatment with other chemotherapeutic or biologic agents. Preliminary safety information from the CALGB10101 clinical trial conducted in the United States reported 6 infection-related deaths out of 51 patients who received fludarabine plus rituximab (FR) followed by consolidation therapy with alemtuzumab. The potential for an increased risk of infection-related complications may exist following treatment with multiple chemotherapeutic or biological agents. The phase 2 CALGB10101 clinical trial is an ongoing study investigating the administration of induction chemotherapy with FR followed by alemtuzumab for remission consolidation in previously untreated symptomatic patients with B-cell chronic lymphocytic leukaemia (B-CLL). The induction regimen in this study consisted of fludarabine 25 mg/mē intravenously (IV) on days 1 to 5; rituximab escalated from 50 mg/mē on day 1 to 325 mg/mē on day 3, to 375 mg/mē on day 5 (cycle 1) and then 375 mg/mē IV on day 1 of cycles 2 to 6; every 28 days for up to 6 cycles. Approximately 4 months after the last dose of fludarabine, patients with stable or responsive disease were to receive consolidation therapy with subcutaneous alemtuzumab 3 mg on day 1; 10 mg on day 3; 30 mg on day 5; and 30 mg 3 times weekly thereafter for 6 weeks. The study reported 6 infection-related deaths out of 51 patients who received the 3 chemotherapeutic agents (FR induction and consolidation with alemtuzumab). The 6 fatal infections were reported as viral meningitis, listeria meningitis, Legionella pneumonia, cytomegalovirus (CMV) infection, Pneumocystis jiroveci pneumonia (PCP), and Epstein Barr virus (EBV) associated lymphoproliferative disorder. Bayer HealthCare and Genzyme were also informed of an additional non-infection related fatality, believed to be transfusion-associated graft versus host disease (TAGVHD), which occurred in a nonlymphopenic patient who had received nonirradiated blood products. The use of alemtuzumab consolidation therapy in CLL is an area of active investigation. Moreover, the design of the CALGB10101 study did not allow for a direct assessment of the relative contribution of any 1 of the agents in this regimen (including alemtuzumab). Fludarabine, rituximab, and alemtuzumab all have known immunosuppressive properties, and it is possible that the infectious complications that occurred in this trial are the result of a prolonged period of immunosuppression resulting from the sequencing of these drugs without sufficient time for recovery. The risk may also be influenced by the induction regimen and/or dose or schedule of the agents used. The relative contribution of each drug to the safety outcomes in this study is not clear based on the available data. The alemtuzumab Canadian Product Monograph will be updated to reflect this safety information. Any occurrence of serious and/or unexpected adverse reactions in patients receiving alemtuzumab should be reported to Bayer HealthCare or Health Canada at the following addresses: Bayer HealthCare Canada Vigilance Program SOURCE: Health Canada
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