A Multi-Centre Randomized and Double-Blind Controlled Trial of Rituximab for Warm Autoimune Hemolytic Anemia in Adults

• Published in: Blood 2015-12, Vol.126 (23), p.3338-3338
• Main Authors: Michel, Marc, Terriou, Louis, Roudot-Thoraval, Françoise, Hamidou, Mohamed, Ebbo, Mikael, Le guenno, Guillaume, Audia, Sylvain, Royer, Bruno, Morin, anne-Sophie, Michot, Jean Marie, Jaccard, Arnaud, Frenzel, Laurent, Haioun, Corinne, Khellaf, Mehdi, Godeau, Bertrand
• Format: Article
• Language: English
• ISSN: 0006-4971; 1528-0020
• DOI: 10.1182/blood.V126.23.3338.3338

▪ Introduction: Warm autoimmune hemolytic anemia (wAIHA) is a rare autoimmune disease that can be life threatening especially in elderly patients. Rituximab has shown very promising efficacy in several uncontrolled studies and in one controlled trial for treating adult' wAIHA and it is commonly used off-label as a second-line treatment and as a corticosteroid-sparing agent. Methods: This phase 3 multicentre randomized (1/1 ratio) and double-blind controlled trial aimed to assess the efficacy and safety of rituximab compared to placebo for the treatment of adults with newly diagnosed wAIHA treated with prednisone. Inclusion criteria were: age ≥ 18 years with a confirmed diagnosis of wAIHA (hemoglobin level ≤ 10g/dL with hemolysis and a positive direct antiglobulin test with an anti-IgG ± anti-C3d pattern in the absence of any other cause of hereditary or acquired hemolytic anemia). Only patients previously treated with corticosteroids for less than 6 weeks could be included. Patients with secondary wAIHA (except for stage A chronic lymphocytic leukemia) were excluded. At time of inclusion, all patients were given prednisone at a daily dose of 1 mg/kg for 2 weeks and then tapered every 10 days according to a standardized procedure and stopped within 3 months in case of response. Eligible patients received in combination with prednisone (double-blind) 2 infusions of either rituximab (arm A) or placebo (arm B) at a fixed dose of 1,000 mg 2 weeks apart (on days 1 and 15 after randomization). The primary endpoint was the overall response rate (CR + PR) at 1 year in both arms. Complete remission (CR) was defined by a hemoglobin (Hb) level ≥11 g/dL (women) or 12 g/dL (men) without hemolysis (including a normal haptoglobin level) in the absence of any ongoing treatment for wAIHA, on 2 different occasions 4 weeks apart in the absence of recent transfusion. Partial remission (PR) was defined by a Hb level ≥ 10g/dL with at least a 2g increase from baseline in the absence of any other treatment than prednisone given at a daily dose ≤ 10 mg or recent transfusion. A non-response (NR) was defined by the need of receiving prednisone at a daily dose > 10mg to maintain a PR and/or any other treatment potentially active in wAIHA (i.e., splenectomy, immunosuppressors). The hypothesis for the calculation of the sample size (n = 32 patients, 16 in each arm) was, based on previous data from the literature, an 80% overall response rate (CR + PR) at 1 year in the RTX arm versus 20%