Eltrombopag Combining Rituximab Versus Eltrombopag for Treatment of Adult Immune Thrombocytopenia: A Single Center, Retrospective Cohort Study

Introduction: Immune thrombocytopenia (ITP) is the most common hematological acquired hemorrhagic disease characterized by antibody-mediated platelet destruction and/or megakaryocyte maturation disorders. Eltrombopag and other thrombopoietin receptor agonists can rapidly increase the platelet count of patients with ITP by promoting megakaryocyte maturation and immune regulation, and effectively reducing the risk of bleeding. However, platelet levels often fall to baseline levels in the short term after drug withdrawal. Rituximab prevents the excessive destruction of platelets in patients by eliminating the autoantibody-secreting B cells. Although it takes a long time to act, some patients can achieve long-term remission. To explore the feasibility of the combination of two drugs with different mechanisms, we retrospectively analyzed the efficacy and safety of patients treated with eltrombopag combined with rituximab or eltrombopag monotherapy in our center.

Methods: Collected the clinical data of patients with immune thrombocytopenia admitted to our center from October 2017 to December 2021. Patients included in the analysis were required to meet the following inclusion and exclusion criteria: 1) aged more than 18 years; 2) without acute infection, liver or kidney injury; 3) without high-risk factors for thrombosis; 4) not accompanied by severe immunodeficiency disease. All patients accepted eltrombopag or a combination regimen with rituximab. The initial dose of eltrombopag was 50mg/75mg daily, and the combination group received an intravenous infusion of rituximab (375mg/m2, once) within 1 month of the initiation of eltrombopag. During follow-up, the dose of eltrombopag was adjusted according to the patient's platelet count. The primary endpoints were complete response (CR), response (R), and overall response (OR) after 8 weeks, 12 weeks, and 24 weeks of treatment. Platelet counts should be confirmed on two separate occasions at least 7 days apart when defining responses (CR: platelet count ≥ 100×10⁹/L and absence of bleeding; R: platelet count ≥ 50 × 10⁹/L and at least a doubling of baseline and absence of bleeding; OR: platelet count ≥30 × 10⁹/L or ≥2-fold increase of the baseline platelet count or bleeding). Secondary endpoints included sustain response off therapy (SRoT), duration of response, and adverse events (AEs).

Results: 152 patients were enrolled in our study, 80 patients received eltrombopag plus rituximab and 72 patients received eltrombopag monotherapy. 6 patients in the combination group, and 9 patients in the monotherapy group did not receive the allocated intervention (5 and 7 for adding other treatments, 1 and 2 due to the diagnosis change). 5 and 10 lost to follow-up in combination and monotherapy groups, respectively. Eventually, 69 patients in the eltrombopag plus rituximab group and 53 patients in the eltrombopag group analyzed the efficacy and safety. The median follow-up time was 46 weeks (4-177w) vs 30 weeks (4-190w), respectively. Results showed that after 12 weeks and 24 weeks of treatment, the percentage of patients who reached R in the combination group was higher than in the monotherapy group (72.3% vs 54.0%, P=0.042; 70.0% vs 50.0%, P=0.041). And the OR after 12 weeks of treatment was also higher in the eltrombopag plus rituximab group (80.0% vs 64.0%, P=0.055). 17 patients (24.6%) in the combination group, and 5 patients (9.4%) in monotherapy can discontinue the eltrombopag successfully and maintain the platelet count ≥30 × 10⁹/L for more than 2 months (P=0.03). There was no significant difference in the incidence of abnormal liver function and infection between the two groups (P>0.05). 11 patients (15.9%) reported medicated alopecia and 1 patient developed deep vein thrombosis of the lower extremity.

Conclusion: The combination of eltrombopag and rituximab was safe and active in patients with immune thrombocytopenia, showing a sustained response, some patients can be successfully discontinued. This regimen provides a new possibility of drug combination therapy with different mechanisms for the long-term efficacy of ITP.

No relevant conflicts of interest to declare.