Ryan K DasGupta1, Lauren Levine2, Tracy Wiczer1, Spero Cataland3. 1. 1 Department of Pharmacy, The Ohio State University James Cancer Hospital, Columbus, OH, USA. 2. 2 Department of Pharmaceutical Services, Vanderbilt-Ingram Cancer Center, Nashville, TN, USA. 3. 3 The Ohio State University James Cancer Hospital, Columbus, OH, USA Division of Hematology & Oncology.
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 × 109/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 × 109/L and ≥50 × 109/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 × 109/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 × 109/L in a median of 2 days versus 4.5 days for Cohort 1. More patients in Cohort 2 achieved a platelet ≥ 30 × 109/L (42.9% vs. 25%) and platelet ≥ 50 × 109/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.
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 × 109/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 × 109/L and ≥50 × 109/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 × 109/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 × 109/L in a median of 2 days versus 4.5 days for Cohort 1. More patients in Cohort 2 achieved a platelet ≥ 30 × 109/L (42.9% vs. 25%) and platelet ≥ 50 × 109/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.
Authors: Maria L Lozano; Maria E Mingot-Castellano; María M Perera; Isidro Jarque; Rosa M Campos-Alvarez; Tomás J González-López; Gonzalo Carreño-Tarragona; Nuria Bermejo; Maria F Lopez-Fernandez; Aurora de Andrés; David Valcarcel; Luis F Casado-Montero; Maria T Alvarez-Roman; María I Orts; Silvana Novelli; Nuria Revilla; Jose R González-Porras; Estefanía Bolaños; Manuel A Rodríguez-López; Elisa Orna-Montero; Vicente Vicente Journal: Sci Rep Date: 2019-11-13 Impact factor: 4.379