Combination Therapy with Romiplostim, Danazol, and a Thrombopoietin Receptor Agonist for Immune Restoration in Chronic Refractory Immune Thrombocytopenia: A Case Series

Shi-Xuan Wang,1– 3,* Gen-Mei Tan,1– 3,* Zhi-Ming Zou,1– 3 Li-Fang Zou,1– 3 Ye-Chao Tu,1– 3 Fan-Cong Kong,1– 3 Xing Xie,1 Fei Li1– 3 1Center of Hematology, The First Affiliated Hospital of Nanchang University, Nanchang, People’s Republic of China; 2Jiangxi Clinical Research Center for Hematologic Disease, Nanchang, People’s Republic of China; 3Institute of Lymphoma and Myeloma, Nanchang University, Nanchang, People’s Republic of China*These authors contributed equally to this workCorrespondence: Fei Li, Center of Hematology, The First Affiliated Hospital of Nanchang University, 17 Yongwai Road, Nanchang, Jiangxi Province, 330000, People’s Republic of China, Email [email protected]: Chronic refractory primary immune thrombocytopenia is defined as thrombocytopenia refractory to multiple therapies using second-line agents with or without splenectomy. Patients face the threat of severe bleeding, and it is challenging to achieve effective treatment. Although thrombopoietin receptor agonists (TPO-RAs) and immunomodulators have been established as second-line options, their efficacy as monotherapy remains suboptimal.Methods: Here, we report the early and durable response to a novel triple regimen combining romiplostim, danazol, and either hetrombopag or eltrombopag in two patients with chronic refractory primary immune thrombocytopenia at our center, with a follow-up exceeding 4 months.Results: The bleeding score decreased from grade 3/4 to grade 0 during the follow-up. No significant treatment-related adverse events were observed during the follow-up.Conclusion: Romiplostim in combination with danazol and hetrombopag or eltrombopag may be a safe and efficacious therapy for chronic refractory primary immune thrombocytopenia; however, this needs to be further explored.Keywords: chronic refractory immune thrombocytopenia, TPO receptor agonists, romiplostim, danazol, combination therapy