Although corticosteroids or intravenous immunoglobulin are typical first- and second-line treatments for immune thrombocytopenia (ITP), about one-third of patients do not respond to these therapies. A recent report in Blood, describes a study that uses the combination of rituximab and recombinant human thrombopoietin (rhTPO) to produce a rapid response rate in these difficult-to-treat patients.
"In this situation, the combination of two drugs with a complementary mechanism and time window might be preferable," study authors Hai Zhou, MD, and Ming Hou, MD, from Qilu Hospital at Shandong University in Jinan, China, told ASH Clinical News. The autoimmune disease ITP causes low platelet counts through platelet destruction by platelet antibodies; use of rituximab to interrupt this autoimmune-mediated destruction has been an off-label second- or third-line ITP treatment for more than a decade.
In the current study, led by Drs. Zhou and Hou, the safety and efficacy of rituximab or rituximab + rhTPO, a thrombopoietin mimetic, was evaluated in 115 relapsed or corticosteroid-resistant ITP patients.
The addition of rhTPO led to a greater complete response (CR) rate compared to monotherapy (45.4% vs. 23.7%), though there was no statistical difference between the groups in long-term responses, defined as response lasting for at least six months without any ITP-specific treatments. "In our opinion, the long-term response is mainly dependent on the effect of rituximab," Drs. Zhou and Hou said. "Recombinant human thrombopoietin showed little benefit on sustained response."
The overall response rate was 79.2 percent in the combination therapy group and 71.1 percent in the monotherapy group. Age, gender, and the presence of autoantibodies did not affect response rate or relapse, the authors noted.
Patients in the rituximab + rhTPO group also had a significantly shorter time to response: a median of seven days versus a median of 28 days in the monotherapy group.
Adverse events were generally mild in both groups, with the most common being fever related to upper respiratory, urinary tract, or gastrointestinal infection. The researchers observed an over-representation of rash, headache, stomachache, and chest congestion in the combination therapy group, but no significant difference was seen between the two groups.
One patient (aged >70 years) died of myocardial infarction (MI) at eight months after rhTPO was stopped. Although the investigators said they were uncertain as to the relationship of rhTPO and the case of MI, thrombosis has been previously reported as an adverse event for TPO receptor agonist therapy in ITP patients.
"Patients at risk of thrombosis should be excluded from future clinical trials," they stated, which should also focus on enrolling more patients. "We have a plan to expand the sample size and extend the follow-up time to further evaluate the efficacy and safety of the combination of rituximab and recombinant human thrombopoietin or romiplostim," wrote Drs. Zhou and Hou. "What's more, we intend to carry out some multicenter studies on the combination of other drugs."
Zhou H, Xu M, Qin P, et al. A multicenter randomized open-label study of rituximab plus rhTPO vs. rituximab in corticosteroid-resistant or relapsed ITP. Blood. 2015 January 9. [Epub ahead of print]