Corticosteroids are the guideline-recommended firstline therapy for adult patients with immune thrombocytopenia (ITP), but a recent clinical trial suggests that regulating thrombopoiesis with recombinant human thrombopoietin (rhTPO) could improve platelet production and restore immune tolerance in this population.
In a prospective, multicenter, randomized, controlled trial, investigators questioned whether high-dose dexamethasone and rhTPO would work synergistically to improve platelet response in adults with treatment-naïve ITP. At the 2017 ASH Annual Meeting, Miaomiao Wang, from the Department of Hematology at Qilu Hospital of Shandong University in Jinan, China, and colleagues reported that frontline combination treatment led to higher rates of platelet count restoration, compared with corticosteroids alone.
The study enrolled 245 newly diagnosed, treatment-naïve patients with ITP (age range = 18-75 years) between July 2013 and December 2016 from 25 centers in China. At the time of presentation, 196 patients had undergone randomization. One hundred people were assigned to receive high-dose dexamethasone with rhTPO and 96 to receive high-dose dexamethasone alone.
In both study arms, dexamethasone was given orally at 40 mg a day for four consecutive days. In patients whose disease did not respond, the four-day course of dexamethasone was repeated on days 11 to 14.
In the experimental arm, patients received concomitant 300 U/kg rhTPO subcutaneously daily during the first 14 days. Treatment could be discontinued for patients with platelet counts that recovered to >100×109/L or who experienced an increase of >50×109/L from baseline platelet count.
If participants had platelet counts drop to <10×109/L with active bleeding, use of rescue treatments such as platelet transfusion and hemostatic agents were allowed, at the discretion of the investigator.
Patients were assessed for early response at day 14 (primary endpoint), and study visits were scheduled monthly through the end of month six or until disease relapse. Response was defined as achieving a platelet count ≥30×109/L and at least a two-fold increase of baseline platelet count and absence of bleeding; complete response (CR) was defined as platelet count ≥100×109/L.
At day 14, patients in the combination group had a higher incidence of early response, including CRs, than patients in the high-dose dexamethasone monotherapy arm:
- any response: 89 vs. 64 (89.0% vs. 66.7%; p<0.001)
- CR: 75 vs. 41 (75% vs. 42.7%; p<0.001)
The responses were maintained through six months, the authors reported, and remained higher in the combination group:
- any response: 51 vs. 35 (51% vs. 36.5%; p=0.022)
- CRs: 46 vs. 31 (46.0% vs. 32.3%; p=0.043)
Though high-dose dexamethasone and rhTPO also outperformed high-dose dexamethasone monotherapy on the secondary endpoint of response duration (p=0.04), there were no differences between the groups for time in therapeutic range, bleeding scores, and use of rescue treatments.
There were also no significant differences in the incidence of treatment-related adverse events (AEs) between the two groups, the researchers observed. No patient tested positive for neutralizing antibodies against TPO. Three patients had grade ≥4 AEs in the combination group, including early cerebral hemorrhage (n=2) and cerebral infarction (n=1). One patient died because of early cerebral hemorrhage; none of these events were deemed treatment-related. No patient tested positive for neutralizing antibodies against TPO.
“Our findings suggest that the addition of rhTPO to high-dose dexamethasone is superior to high-dose dexamethasone monotherapy in the treatment of newly diagnosed treatment-naïve adult [patients with] ITP,” the researchers concluded. “Thus, this combination can be a feasible frontline therapy in [this patient population].”
The use of investigator’s decision to guide rescue treatment may have introduced bias and limited the study’s findings.
The authors report no financial conflicts.
Wang M, Qin P, Zhou F, et al. Recombinant human thrombopoietin (rhTPO) and high-dose dexamethasone (HD-DXM) versus high-dose dexamethasone monotherapy as frontline treatment in newly diagnosed adult immune thrombocytopenia (ITO): a prospective, multicenter, randomized controlled trial. Abstract #13. Presented at the 2017 American Society of Hematology Annual Meeting, December 9, 2017; Atlanta, GA.