Sustained response to low-dose rituximab in idiopathic autoimmune hemolytic anemia

ObjectivesTo evaluate the sustained response to low-dose (LD) rituximab in autoimmune hemolytic anemia (AIHA), the ex vivo effect on anti-RBC antibody production by mitogen-stimulated direct antiglobulin test (MS-DAT), and the in vitro dose effect of the drug on the production of anti-RBC antibodies. MethodsThirty two patients, 18 warm (W) AIHA and 14 cold hemagglutinin disease (CHD), were treated with LD rituximab (100mg fixed dose x4 weekly infusions) along with a short course of oral prednisone. Complete clinical examination, blood counts, and hemolytic markers were performed at enrollment and at month 6, 12, 24, and 36. ResultsHematological parameters significantly improved at all time points compared to enrollment. The overall response was 90%, 100%, 100%, and 89% and the relapse-free survival 87%, 79%, 68%, and 68% at 6, 12, 24, and 36months, respectively. Response rates were slightly better in WAIHA than in CHD, and relapse risk was greater in cold than warm forms (HR 2.1, 95% CI 0.6-7.9). Four patients were retreated (one patient twice), all achieving a response, lasting a median of 18months (range 9-30). Treatment was well tolerated without adverse events or infections. Anti-RBC antibody production by MS-DAT significantly decreased over time. In vitro studies showed that rituximab effectively inhibited anti-RBC antibody production at 50g/mL, 1/6 of the drug concentration after therapy with standard doses. ConclusionsThese data confirm that LD rituximab treatment is effective and induces sustained responses in AIHA, and that a lower dose of the drug is enough to down-regulate autoantibody production.