Rituximab Maintenance Treatment In Immune Mediated Thrombocytopenia (ITP) Including Evans Syndrome
Authors: Mahler Michelle , Hasan Aisha , Bussel James B. 
Published: October 2019

Abstract
Abstract 2523

Background:
Rituximab is a chimeric human-murine anti CD 20 antibody that results in B cell depletion. In patients with ITP, the current regimen of 375mg/m2 once a week for 4 weeks, has been shown to result in disease improvement in up to 60% of patients and a complete response in 30–40% of patients. In patients who relapse, a repeat course of rituximab is given but there is no data currently available on its use as a maintenance therapy. In 2009 Hasan et al reported on 20 patients who relapsed following an initial response to rituximab, treating them with the standard regimen (4 infusions). Repeat standard dose rituximab resulted in significant responses in 15 of the 20 patients, which were similar in duration of effect to those seen with the initial infusions (1). Since it thus seemed predictable that there would be a relapse after a second response and the approximate time to relapse could be estimated, we elected to study a maintenance rituximab regimen in patients who had responded to rituximab previously and relapsed. Recent data on the safety of prolonged rituximab use has been shown that it prolongs survival in patients with lymphoma with minimal additional side effects.

Results:
Ten patients (6 male and 4 female) with refractory ITP who had previously responded to rituximab were included in this study. The median age at diagnosis was 14.5 years and the median time to treatment with maintenance rituximab was 78 months. Five out of the 10 patients had Evans syndrome and 7 of the patients had had a prior splenectomy. The median starting platelet count was 7×109/l. Five of the patients received the first round of 4 weekly doses followed by 1 dose of rituximab every 4 months for 6 doses. All 5 of these patients remain in remission and do not require any treatment currently. They range from having finished the last infusion 2 months ago to 26 months ago; thus far 3 of the patients are past their expected relapse time based on their duration of response to their previous cycle of rituximab. One patient relapsed on treatment, received 2 doses of IVIG, and maintains a platelet count > 100,000/uL, more than 3 years from last treatment. Two patients are still on treatment. Two female patients discontinued rituximab after 4 maintenance infusions due to pregnancy or an expectation of pregnancy. No patient suffered any bleeding episodes, nor did any of them suffer from unusual infectious complications, hepatitis B, or progressive multifocal leukoencephalopathy (PML). One patient is mildly hypogammaglobulinemic but is not on IVIG.

Conclusion:
In this group of 10 of patients with refractory ITP, all followed for more than 2 years on study and who all previously responded to their initial 4 infusions of rituximab before relapsing, it appears that rituximab maintenance is a safe and effective therapeutic option. If the responses continue to be substantially longer than those seen with the initial rituximab course, this could become an optimal therapeutic approach to patients with ITP who respond to but relapse after rituximab treatment. One potential mechanism is that with B cell depletion by rituximab, autoreactive B cells are also depleted, thereby resulting in decreased “cross talk” between autoreactive B and T cells. Other mechanisms are possible and under study.

Reference:
1) Am. J. Hematol. 84:661-665,2009
Patient Characteristics

Disclosures:
Off Label Use: use of rituximab as a therapy in ITP. Bussel:Amgen: Equity Ownership, Membership on an entity's Board of Directors or advisory committees, Research Funding; Cangene: Research Funding; GlaxoSmithKline: Equity Ownership, Membership on an entity's Board of Directors or advisory committees, Research Funding; Genzyme: Research Funding; Immunomedics: Research Funding; Ligand: Membership on an entity's Board of Directors or advisory committees, Research Funding; Eisai Inc: Membership on an entity's Board of Directors or advisory committees, Research Funding; Shionogi: Membership on an entity's Board of Directors or advisory committees, Research Funding; Sysmex: Membership on an entity's Board of Directors or advisory committees, Research Funding; Portola: Consultancy.