Successful Detection and Management of Immune Thrombocytopenia in Alemtuzumab-Treated Patients with Active Relapsing-Remitting Multiple Sclerosis (P2.198)

OBJECTIVE: Summarize immune thrombocytopenia (ITP) experience with alemtuzumab in core and extension of phase 2 and 3 studies. BACKGROUND: Alemtuzumab improved clinical efficacy versus subcutaneous interferon beta-1a in active relapsing-remitting multiple sclerosis (RRMS) patients with a consistent, well-characterized safety profile. Following index case of ITP (diagnosed after fatal intracranial hemorrhage), increased surveillance (eg, monthly platelet counts and ITP signs and symptoms) and patient and physician education about the autoimmune disorder ITP were implemented. DESIGN/METHODS: In 36-month phase 2 CAMMS223 and 24-month phase 3 CARE-MS core studies, active RRMS patients (treatment-naive [CAMMS223, CARE-MS I] or relapsed on prior therapy [CARE-MS II]) received alemtuzumab 12 or 24 mg/day (CARE-MS I, 12 mg/day only) intravenous infusions at baseline and 12 months later. Patients could enter extension study for ongoing follow-up and as-needed alemtuzumab re-treatment. ITP cases were identified by investigator-reported adverse events and platelet-based criteria. RESULTS: As of November 26, 2012, of identified cases, 21 were considered medically confirmed ITP using a standardized definition (Rodegheiro, 2009) and without alternative plausible etiology, for incidence of 1.4% (21/1486); 80% of post-index cases were detected through monthly blood monitoring and 20% through patient recognition of signs and symptoms. Excluding the index case, all patients had sustained responses to therapy. Most patients (70%) completely responded to first-line therapy; 20% required further, second-line therapy. One patient had spontaneous resolution; one refractory to first-line therapy, underwent splenectomy. ITP monitoring compliance was high; 96.5% of total expected monthly blood tests were completed. Updated data are being presented at conference. CONCLUSIONS: The autoimmune disorder ITP was associated with alemtuzumab treatment for MS and characterized by occurrence within 48-month timeframe after last infusion and durable remissions after therapy. Laboratory monitoring and education programs continue to ensure early detection (before major bleeding manifestation) and successful management. Study Supported by: Genzyme, a Sanofi company, and Bayer Healthcare Pharmaceuticals Disclosure: Dr. Cuker has received personal compensation for activities with Baxter, Bayer Pharmaceuticals Corp., Daiichi Pharmaceutical Corp., and Genzyme Corp. Dr. Cuker has received research support from Stago. Dr. Stasi has received personal compensation for activities with Amgen Inc., GlaxoSmithKline Inc., and Genzyme Corp. Mr. Palmer has received personal compensation for activities with Genzyme Corporation as an employee. Dr. Oyuela has received personal compensation for activities with Genzyme Corporation as an employee. Dr. Margolin has received personal compensation for activities with Genzyme Corp. as an employee. Dr. Bass has received personal compensation for activities with Sanofi-Aventis Pharmaceuticals Inc., Novartis, Teva Neuroscience, Biogen Idec, Ascend Therapeutics, Quest. Dr. Bass has received research support from Sanofi-Aventis Pharmaceuticals Inc., Teva Neuroscience, Biogen Idec, Novartis, and Roche Diagnostics Corporation.