Immunomodulation and immune thrombocytopenia: some unmet needs, questions, and outlook

During the last two decades, new therapeutic strategies have been developed, particularly anti-CD20 agents and thrombopoietin-receptor (TPO-r) mimetics, for immune thrombocytopenia (ITP). However, although the new efficient drugs have deeply modified the therapeutic strategy and the disease prognosis, there are still unmet needs and challenges. Concerning rituximab, reassuring data concerning its safety have recently been reported. The main limitation of the treatment is its modest long-term efficacy, with frequent disease relapse. Maintenance treatment or association with other immunomodulatory drugs such as dexamethasone may achieve better long-term response. With failure of one of the available TPO-r agonists (ie, romiplostim and eltrombopag), another can be used. Switching may be beneficial, with more than 50% chance of response, and could limit the risk of platelet fluctuation occasionally observed with these treatments. According to the mechanism of action of TPO-r agonists, a rapid relapse of thrombocytopenia should be observed after they are stopped. Several recent observational studies suggested sustained responses in patients achieving complete response with TPO-r agonists and who stopped the treatments. Prospective studies to confirm these unexpected data are needed. Thrombosis in ITP is a concern, particularly with TPO-r agonists, even though the pivotal studies of eltrombopag and romiplostim did not report a higher incidence of thrombosis events with TPO-r agonists than placebo. Despite these reassuring data, the risk of thrombosis with TPO-r agonists remains unanswered, particularly with secondary ITP or in older adults.