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Rituximab Treatment in Patients With Immune Thrombocytopenic Purpura

Rituximab Treatment in Patients With Immune Thrombocytopenic Purpura

Immune thrombocytopenic purpura (ITP) in adults is a chronic autoimmune disease characterized by antiplatelet antibody (APA)-mediated thrombocytopenia. The aim of treatment is to maintain a safe platelet count with minimal toxicity. Rituximab (Rituxan) is a chimeric anti-CD20 monoclonal antibody that depletes B lymphocytes and is used to treat patients with B-cell lymphomas. There is little toxicity apart from first infusion reactions, which are rarely severe. As ITP is an antibody-mediated disease, this trial aimed to assess the efficacy of rituximab in adults with primary ITP refractory to multiple treatments with platelet counts below 30,000/µL. Patients received 375 mg/m² of rituximab weekly for 4 weeks. Response was defined as a platelet increase to more than 50,000/µL. A total of 21 patients have enrolled, 14 of which have been followed for more than 10 weeks and are summarized in the table below:

Of 14 patients, 8 (57%) responded a median of 3.5 weeks (range: 1-15 weeks) from first infusion; all are still maintaining platelets above 50,000/µL at a median of 25 weeks follow-up. Of those eight, five achieved complete remission (CR) at a median of 14 weeks. Males, patients diagnosed with ITP for < 3 years, and those with higher initial platelet counts were more likely to respond. Only one patient (number 13 in the table) had detectable CD19-positive lymphocytes by week 12 of treatment.

There were no serious infections and no significant change in immunoglobulin (Ig) levels. Of 21 patients, 8 experienced transitory first infusion reactions such as red face, hives, itching, and throat discomfort. Two patients have a T-cell clone (one responder and one nonresponder) and one a B-cell clone (nonresponder). The clones did not disappear after treatment. IgM and IgG APA levels are being assessed.

CONCLUSION: In summary, 57% of adults with difficult ITP have responded to treatment, with 36% in CR. Rituximab is especially useful because of its long duration of response in both patients with recently diagnosed ITP, allowing responders to postpone splenectomy, and also in patients refractory to standard therapies. The mechanism of action of rituximab in ITP is unclear. The timing of response makes it unlikely that response is only related to decreased levels of APA, as antibody-producing plasma cells, especially IgG-producing, infrequently express CD20.

Click here to read Dr. Bruce Cheson's commentary on this abstract.

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