Romiplostim, Low-Dose Rituximab and High-Dose Dexamethasone Combination in Newly Diagnosed Immune Thrombocytopenia: Another "Total Therapy" Pilot Study

Abstract

Background: Primary immune thrombocytopenia (ITP) is an acquired autoimmune disorder that results from accelerating platelet clearance, destruction, and production. Front-line therapy for newly diagnosed ITP includes corticosteroids, intravenous immune globulin, or anti-D immunoglobulin. However, after these single-agent therapies, relapses will occur in half of patients. We previously reported the safety, feasibility, and efficacy of the combination of dexamethasone, low-dose rituximab, and the thrombopoietin receptor agonist (TPO-Ra) eltrombopag as front-line treatment in newly diagnosed ITP. Romiplostim, another TPO-Ra is approved by the FDA for patients with chronic ITP. However, the safety, tolerability, and efficacy of romiplostim combined with low-dose rituximab, and high-dose dexamethasone in newly diagnosed ITP remain unknown. Objective: Our primary objectives were safety, and tolerability. Secondary objectives were initial response and relapse incidence. Methods: An open-label, single-arm study was performed in Hospital Universitario "Dr. José Eleuterio González" in Monterrey, Mexico (Clinical trials.gov NCT04588194). Eligible patients were newly diagnosed ITP patients, treatment-naïve, ≥18 years, with a platelet count ≤30×10 9/L. Patients were excluded if they had an active infection, pregnancy, or malignant disease. The treatment regimen was romiplostim (2 mcg/kg weekly, four doses), low-dose rituximab (100 mg weekly, four doses) and high-dose dexamethasone (40 mg PO, days 1-4). Dexamethasone was allowed up to 3 cycles. Partial (PR) and complete responses (CR) were defined as an increase in platelet counts ≥30×10 9/L (at least a doubling of the baseline count) and ≥100×10 9/L, respectively. Results: We included ten consecutive patients. The median age was 34.5 years (range, 17-63). Seven patients were men (70%). The median platelet account at diagnosis was 6x10 9/L (range 0-23), and median follow-up was 180 days (range 30-270). The median number of romiplostim doses was 3.5 (range 1-4), and three (30%) patients required dose adjustment due to thrombocytosis. All but one patient achieved response (CR or PR) at a median of 7 days (range 7-28). Five patients (50%) achieved CR at 28 days of treatment, and four patients (40%) PR. No significant adverse effects have occurred during treatment; one patient presented grade 1 myalgia and the other a grade 2 soft tissue infection. Five patients (50%) relapsed during follow-up. Recently, four (40%) patients remain in CR and three (30%) in PR. Conclusion: The combination of romiplostim, low-dose rituximab, and high-dose dexamethasone was safe and effective. This "total therapy" approach was associated with minimum side effects and rapid initial response. Prospective validation in a larger sample is needed. Figure 1 Figure 1. Disclosures Gomez-Almaguer: Janssen: Honoraria, Speakers Bureau; Roche: Honoraria, Speakers Bureau; Bristol-Myers-Squibb: Honoraria, Speakers Bureau; Takeda: Honoraria, Speakers Bureau. OffLabel Disclosure: Romiplostim in firs-line therapy for immune thrombocytopenia

Thrombopoietin receptor agonist and rituximab combination therapy in patients with refractory primary immune thrombocytopenia

“…It is the only TPO-RA, which is administered subcutaneously and its initial dose is 1 mg/kg per week, with dose adjustments according to platelet response [42,43]. [46]. Furthermore, Kikuchi et al [47] concluded in their study that addition of rituximab to standard therapy (romiplostim and splenectomy) decreases treatment costs and increases efficacy in ITP adults in Japan, compared with the ones in standard therapy.…”

“…Colunga-Pedraza et al in their pilot study showed that all but one patient who received rituximab (100 mg weekly, four doses) and romiplostim (2 μg/kg weekly, four times a week) and dexamethasone (40 mg p.o. days 1–4) achieved response (CR or PR) at a median of 7 days [46]. Furthermore, Kikuchi et al [47] concluded in their study that addition of rituximab to standard therapy (romiplostim and splenectomy) decreases treatment costs and increases efficacy in ITP adults in Japan, compared with the ones in standard therapy.…”

How we treat primary immune thrombocytopenia in adults

“…Several single-arm studies reported that HD-DXM in combination with eltrombopag had favorable SRR at 6 months (56.5–75%) and good tolerability in newly diagnosed treatment-naïve ITP patients [ 111 , 112 ]. In addition, more intensified strategies using the combination of eltrombopag or romiplostim, low-dose rituximab, and HD-DXM have been proposed and tested in small pilot studies [ 113 , 114 ]; however, the improvement in relapse-free survival yielded by the three-drug combination still needs validation. In a large prospective RCT, we recently showed that HD-DXM plus a limited course of recombinant human thrombopoietin (rhTPO) elicited a higher response rate at day 14 and month 6, and a slightly higher treatment-free remission rate thereafter than HD-DXM monotherapy [ 115 ].…”