Alemtuzumab and Rituximab in the treatment of refractory autoimmune Cytopenias.

The combination of rituximab and alemtuzumab have been used to treat CLL. This combination is feasible without excessive toxicity. Both antibodies have been used as monotherapy for the treatment of autoimmune diseases, including autoimmune hemolytic anemia (AHA) and Immune thrombocytopenic purpura (ITP).

Evaluate the efficacy and safety of the combination of low dose alemtuzumab and rituximab in patients with AHA and ITP.

patients diagnosed with AHA (clinical and biochemical data of hemolysis) or ITP (less than < 50 K/μl) who failed or relapsed after first line therapy (steroids) were included. Basal lymphocyte count and immunoglobulin levels were assessed. Patients received alemtuzumab 10 mg SC on days 1,2 and 3 followed by rituximab 100 mg IV on days 4,11,18 and 25. Complete response (CR) was defined as normal hemoglobin in the absence of hemolysis and platelet count >150K/μl; and partial response (PR): increase of 2 g/dl of hemoglobin and platelets 50-149K/μl The effect of the antibodies combination was evaluated by lymphocyte B, T and NK count 8 and 24 weeks after their administration. Prophylactic bactrim, acyclovir and itraconazole were given for the first 2 months.

We included 13 patients, and eleven were evaluable, 5 patients in the AHA group and 6 in the ITP group, demographic data is shown on table 1. For AHA the 5 patients achieved CR with a median follow up of 37 weeks; only 1 patient relapsed after the 49^th week of follow up. For the ITP group 2 patients achieved CR, 2 patients PR and 2 were classified as non responders. Alemtuzumab and rituximab combination quickly depleted B lymphocites falling to zero or near zero at the 8^th week determination, with a sustained decrease at 24^th week, in which levels did not return to pre-treatment levels.

These initial results indicate that low dose alemtuzumab and rituximab combination is safe and demonstrate promising activity for AHA and ITP refractory patients including durable complete responses and as a steroid spring therapy.

Off Label Use: alemtuzumab for refractory autoimmune cytopenias rituximab for refractory autoimmune cytopenias.