PB1348 - Thrombopoietin receptor agonist and rituximab combination therapy in patients with refractory primary immune thrombocytopenia. A single-center study

Background: Immune thrombocytopenia (ITP) is an autoimmune disorder causing platelet level (PLT) below 100x109/L and bleeding of variable severity. The first line of treatment is corticosteroids or intravenous immunoglobulins. The second line consists of rituximab, thrombopoietin receptor agonists (TPO-RA) or splenectomy and less robust evidence like immunosuppressants, danazol, vinca alkaloids. There is an ongoing discussion regarding management of refractory ITP. One of the emerging therapies is the combination of TPO-RA with rituximab. TPO-RA stimulate megakaryocytes to proliferate and increase platelet production whereas rituximab, anti-CD20 monoclonal antibody, reduces antiplatelet antibody production. This addresses both mechanisms essential in pathophysiology of ITP.

Aims: We investigate efficiency of TPO-RA and rituximab combination therapy in treatment of patients with refractory primary ITP

Methods: From the database of General Hematology Department, Copernicus Memorial Hospital in Lodz, Poland, we found patients to the retrospective study who received TPO-RA (maximum dose) and rituximab (375 mg per m2 once a week 4 doses) as combined therapy. After collapsed platelet response with TPO-RA, rituximab was added with continuation of TPO-RA. Next, we analyzed the response rate.

Results: 8 patients were enrolled to the study, median age 38, 62,5% male, 4-12 previous treatment lines. Rituximab concomitant treatment was 25% eltrombopag, 12,5% avatrombopag and 62,5% romiplostim. After 1 month, the complete response (CR1, PLT>100G/l) was achieved in 62,5% patients, and response (R1, PLT>30G/l) was achieved in 75% patients. Adequately, after 6 months CR6 and R6 was 75% and 87,5%. Treatment-free response 6 months after completion (TFR6) was in 25% of patients.

Conclusion(s): The study group achieved response to treatment, which suggests that combination of TPO-RA and rituximab is effective. Using two different drugs mechanisms is a good option for patient with refractory ITP. However, prospective study on large group of patients is needed to better evaluate the efficiency of this treatment.