Initial romiplostim dosing and time to platelet response in patients with treatment refractory immune thrombocytopenia

Abstract

Background/rationale Romiplostim is a thrombopoietin receptor agonist recommended as a second-line therapy for immune thrombocytopenia. An initial dose of 1 mcg/kg/week subcutaneously with weekly 1 mcg/kg dose escalation is recommended per package labeling. Optimizing romiplostim dosing for hospitalized, corticosteroid- and intravenous immunoglobulin-refractory patients with severe thrombocytopenia secondary to immune thrombocytopenia may be critical for improving platelet responses, reducing the risk of bleeding, and decreasing hospital length of stay. Limited data are available evaluating the efficacy and safety of higher initial doses. Objective The primary objective of this study was to compare the time to platelet ≥ 10 × 10/L between patients who received an initial romiplostim dose of ≥2 mcg/kg/week compared to the standard initial dose of 1 mcg/kg/week. Secondary objectives included time to platelet response ≥ 30 × 10/L and ≥50 × 10/L, percentage of patients achieving platelet responses, hospital length of stay, and incidence of adverse events and bleeding complications. Methods This was a retrospective, single-center, cohort study including hospitalized adults with corticosteroid- and intravenous immunoglobulin-refractory immune thrombocytopenia. A baseline platelet < 10 × 10/L was required. Patients were stratified by their initial romiplostim dose into Cohort 1 (1 mcg/kg/week) and Cohort 2 (≥2 mcg/kg/week). A review of electronic medical records and descriptive statistics generated findings. Results A total of 18 patients were included, 4 in Cohort 1 and 14 in Cohort 2. Patients in Cohort 2 had a median initial dose of 4.5 mcg/kg/week. Patients in Cohort 2 achieved a platelet ≥ 10 × 10/L in a median of 2 days versus 4.5 days for Cohort 1. More patients in Cohort 2 achieved a platelet ≥ 30 × 10/L (42.9% vs. 25%) and platelet ≥ 50 × 10/L (28.6% vs. 25%). The median hospital length of stay was shorter in Cohort 2 (13.5 vs. 20 days). Clinically relevant nonmajor bleeding was noted less frequently in Cohort 2 (28.6% vs. 75%), while major bleeding was more frequent in Cohort 2 (14.3% vs. 0%). No thrombotic events occurred. Conclusion Our study suggests that higher initial romiplostim doses may be safe for hospitalized patients with treatment-refractory immune thrombocytopenia. Compared to Food and Drug Administration-approved dosing, higher initial doses may shorten time to platelet responses and hospital length of stay. Further large-scale studies are needed to confirm these findings.

Deciphering predictive factors for choice of thrombopoietin receptor agonist, treatment free responses, and thrombotic events in immune thrombocytopenia

“…This suggests that the prescription of the TPO-RA could be related to some extent with the risk of bleeding before initiating treatment. In these situations, romiplostim is given preferentially to patients, probably based on the wider dosage range of the drug that may allow earlier responses with higher doses, as suggested in a small sample size study 21 . Additionally, the subcutaneous administration avoids potential dietary interferences, and adherence to treatment is secured.…”

The role of romiplostim for pediatric patients with immune thrombocytopenia

“…25 In a small study of hospitalized adult ITP patients, relative to patients initiated at romiplostim at 1 µg/kg/week, patients initiated on romiplostim at a median starting dose of 4.5 µg/kg/week had fewer bleeding events, a shorter hospital length of stay, and improved rates of achieving a platelet count ⩾ 50 × 10 9 /l with no thrombotic events. 26 For these reasons, the authors routinely start most adult and pediatric patients at 3-5 µg/kg/ week. Similarly, we do not hesitate to titrate the dose by greater than the 1 µg/kg/week instructed by the prescribing information to minimize the total duration of profound thrombocytopenia, the bleeding risk, and the time until an effective dose is achieved.…”

“…25 In a small study of hospitalized adult ITP patients, relative to patients initiated at romiplostim at 1 µg/kg/week, patients initiated on romiplostim at a median starting dose of 4.5 µg/kg/week had fewer bleeding events, a shorter hospital length of stay, and improved rates of achieving a platelet count ⩾ 50 × 10 9 /l with no thrombotic events. 26…”

Romiplostim in adults with newly diagnosed or persistent immune thrombocytopenia

“…Likewise, in a Spanish observational study of patients receiving TPO-RAs, 16% were newly diagnosed and 17% had persistent disease [64]. We identified six real-world studies that specifically examined outcomes in patients with newly diagnosed or persistent ITP [65][66][67][68]73,75]. The results are summarized in Table 2 and support the ability of romiplostim to lead to sustained platelet responses in most patients with newly diagnosed or persistent ITP.…”