Combining an immunomodulatory drug with a TPO‐RA to treat multirefractory ITP patients: The Spanish ITP Group experience

Multirefractory immune thrombocytopenia (ITP) is difficult to manage. The simultaneous administration of an immunosuppressive/immunomodulatory drug (IS/IM) and a thrombopoietin receptor agonist (TPO-RA) is increasingly used. We present the experience of the Spanish ITP Group in this retrospective, observational study. Ninety-seven patients with ≥3 failed treatment lines were administered combination therapy (CT) with an IS/IM and a TPO-RA between January 2021 and December 2023. The IS/IMs were steroids, purine synthesis inhibitors and fostamatinib. The TPO-RAs were romiplostim, eltrombopag and avatrombopag. Seventy-five (77.3%) patients responded to treatment in a median (interquartile range [IQR]) time of 14 (7-52) days. An inverse correlation between previous failures and response was observed (Rho = -0.290, p = 0.009). After 840 (448-1054) days, relapse was reported in 35 (46.7%) of 75 responders (time to relapse: 197 [47-402] days). Relapse was more frequent in chronic ITP patients. Twenty-one patients received a second CT after failure of the first one. Eleven were administered a third CT for the same reason. Response and relapse were similar to those observed with the first CT. Three thromboembolic events and 14 infections that required hospitalization were reported, none fatal. The combination of IS/IMs and TPO-RAs arises as an alternative option of treatment in multirefractory ITP.