Immune thrombocytopenia successfully treated with eltrombopag following multiple therapies including romiplostim

Dear Sir,

We read with great interest the letter by Dr Piccin et al.¹ describing the case of a patient with immune thrombocytopenia (ITP), refractory to multiple treatments (including eltrombopag, a thrombopoietin receptor agonist, TPO-RA), who was successfully cured by a switch to the other TPO-RA, romiplostim.

Refractory ITP is still a clinical challenge, because of the risk of bleeding and mortality. Here we report a case in which romiplostim failed, but that years later was resolved by eltrombopag.

An 84-year old man was admitted to our hospital in January 2008 suffering from a haemorrhagic syndrome characterised by petecchiae, ecchymoses and epistaxis. Blood tests revealed severe thrombocytopenia with a platelet count of 3×10⁹/L and a haemoglobin concentration of 12.6 g/L; the patient’s white blood cell count was normal. The bone marrow aspirate was consistent with a diagnosis of ITP, revealing an increased number of megakaryocytes. There was no platelet response to the first-line treatment with steroids and high-dose intravenous immunoglobulins. Over the following weeks the patient experienced mucocutaneous bleeding and anaemia requiring blood and platelet transfusions. Splenectomy was not considered feasible at that time because of the patient’s advanced age. The man was treated with fixed doses of rituximab of 100 mg/weekly for 4 weeks², without this producing any increase in the platelet count. Subsequently, when the patient experienced more haemorrhagic events, he was treated again with high-dose intravenous immunoglobulins and platelet transfusions. In May 2009 (14 months after diagnosis) he was enrolled in an experimental trial (AMG 531 study) and administered increasing amounts of romiplostim subcutaneosly on a weekly basis. When the maximum dose of 10 μg/kg had been reached with no platelet increase the treatment was suspended. In view of the circumstances, 19 months after being diagnosed, splenectomy was reconsidered. This was eventually performed on the patient without any serious adverse effects but, unfortunately, the ITP was not resolved.

While another major haemorrhage was in course, due to a bladder papilloma, which required blood transfusions, it was decided, 40 months after diagnosis, to start treatment with eltrombopag. After 4 weeks of treatment at a dose of 50 mg/day, a consistent increase in platelet count (>100×10⁹/L) was observed and remains stable 50 months after the diagnosis of ITP. A traumatic femoral head fracture has been successfully treated by a total hip replacement without any haemorrhagic complications. Figure 1 reports the patient’s whole clinical course.

Figure 1.

Sequential treatments and platelet count.

To our knowledge, until recently very few cases, including that reported by Piccin et al. in Blood Transfusion, had described successful switching between the two TPO-RA. However, a recently published study by the French ITP group on the outcome of TPO-RA switching in a large cohort of ITP patients (n=46) found that platelet count was affected in 50% to 80% of patients who switched from romiplostim to eltrombopag or vice versa³. Most authors comment that TPO-RA probably do not cross-react because although the two molecules bind the same receptor, they do so at different sites (romiplostim binds to the surface thrombopoietin receptor domain and eltrombopag to the thrombopoietin receptor transmembrane domain). Since the failure rate in each of the original studies on romiplostim and eltrombopag was 20–40%^4,5, the possibility of replacing the drugs with one another, with no cross-resistance and no side effects, may give ITP patients an additional chance of recovery.