Rituximab Is Highly Effective In The Treatment Of Patients With Autoimmune Blood Cytopenias, Particularly When It Is Followed By a Post-Induction Consolidation / Maintenance Phase

Rituximab is a chimeric anti-CD20 monoclonal antibody, which targets both, autoreactive and neoplastic B-lymphocytes, thus representing a rational therapeutic approach for patients with various autoimmune disorders. However, although rituximab has been used asa treatment option for patients with autoimmune blood cytopenias, its optimal use has not yet been established.

In an effort to analyze the effectiveness and safety of rituximab treatment in this patient population, we have retrospectively analyzed treatment outcome of 147 patients with various autoimmune blood cytopenias or related disorders (AutoImmuneHemolytic Anemia-AIHA N=31, Immune Thrombocytopenic Purpura-ITP N=67, Thrombotic Thrombocytopenic Purpura-TTP N=32, Evans’ Syndrome-ES N=10, Acquired Hemophilia-AH N=4, Anti-Phospholipid Syndrome-APS N=2 and Immune Neutropenia-IN N=1). Eligible patients should have received at least 3 courses of rituximab treatment, unless would have been died earlier due to treatment-related causes.

Patients were 68 male and 79 female, with a median age of 52 years (range 15-87 years) and were treated following 1-7 (median 2) lines of previous treatment, for an early (<12 months, N=42) or a late relapse (>12 months, N=39) or for refractory disease (N=48), at a median of 3.4 months following initial diagnosis (range 0.1-430 months). Eighteen patients received rituximab as first-line treatment due to contra-indication (N=10) or intolerance (N=8) of corticosteroids. Rituximab was administered at the classical dose of 375 mg/m² (N=113) or at a reduced dose of 200 mg/m² (N=26), whereas 8 patients initially received 375 mg/m² for 1-6 cycles and continued with the reduced dose.

Each patient received a median of 6 courses of rituximab (range 1-60 courses). Four out of 143 patients were HBsAg positive, and 62/133 were anti-HBc positive. These patients received lamivudineprophylaxis,throughout rituximab treatment and up to 6 months following rituximab withdrawal. Seven patients (4.8%) received <3 courses of treatment and were not considered evaluable for response. Overall, complete response was achieved by 102 patients (72.9%), partial response by 15(10.7%) whereas 23 patients (16.3%) did not respond. Complete response was 64.5%, 75.4%, 74.2% and 76.5% for patients with AIHA, ITP, TTP and other diseases, respectively. Response rate was similar for patients treated with 375 mg/m² and for those received 200 mg/m² (76/113∼67.3% versus 18/26∼69.2%, respectively, p:n.s) and did not also differ significantly,in relation to patient’s age, previous splenectomy and lines of previous treatment. Four patients received only one treatment course, due to a major allergic reaction or death, unrelated to treatment and were excluded from the analysis. Manageable reactions were observed in at least 13 patients. After a median follow-uptime of 28 months (range 2-143 months), 32 responded patients relapsed (9/26 with AIHA, 14/53 with ITP, 4/25 with TTP, and 5/25 with other diseases). However, only 10/88(11.4%)of the patients, who received post-remission consolidation/maintenance treatment, did relapse, as compared to 21/55 (38.2%)of the patients, who did not receive such a treatment (p<0.01).After a median follow-up time of 45 months, 128 patients are alive, 102 of them in complete response, 14 in partial, and 12 in active/refractory disease. Thirteen patients have died, 8 of them due to causes related to refractory disease and 5 from unrelated causes, and finally 6 patients have been lost from follow-up.

Rituximab represents an effective second-line treatment approach for patients with autoimmune blood cytopenias. The dose of 200 mg/m² is equally effective to the dose of 375 mg/m². Patients receiving post-remission maintenance appear to exhibit more durable and sustained responses.