Combination therapy in relapsed or refractory chronic immune thrombocytopenia: a case report and literature review

Abstract

SUMMARYWhat is known and objective: Immune destruction and decreased platelet production are major components of immune thrombocytopenia (ITP) pathogenesis. The aim of this study was to critically evaluate the role of combination therapy in relapsed/refractory ITP and the concept of medication tapering/discontinuation. Comment: Although a number of combination regimens have been reported, little is published on combining immunosuppression with thrombopoietin receptor agonists (TPO-RAs). We report a case of refractory ITP successfully treated with combination immunosuppression added to eltrombopag. An aggressive combination approach resulted in complete remission and allowed for stepwise drug tapering. What is new and conclusion: Combination immunosuppression can potentiate the effect of TPO-RAs. This mechanistically reasonable strategy could result in a more rapid response than the more popular, sequential, single-agent strategy. Stepwise tapering can be successfully implemented. Comparing sequential single-agent therapy with early combination approach warrants a more extensive study. WHAT IS KNOWN AND OBJECTIVEThe prevailing thought about the pathogenesis of chronic immune thrombocytopenia (ITP) is that a combination of immune destruction of platelets and decreased production results in thrombocytopenia. Immune destruction is due to autoantibody production and increased clearance of platelets by the reticuloendothelial system (RES). The exact mechanism of decreased platelet production remains unclear, although indirect evidence suggests a role for autoantibodies against megakaryocytic precursors.1 Approximately 20% of patients with ITP are refractory to frontline therapy with corticosteroids and, even in patients who respond, relapses are common.2,3 Although 40-60% of patients sustain their response to corticosteroids at 6 months, only a small minority are relapsefree at 1 year.4 Second-line therapy includes, but is not limited to, splenectomy, rituximab and thrombopoietin receptor agonists (TPO-RAs: eltrombopag and romiplostim) with varying degrees of success. A popular strategy for second and later lines of therapy is sequential use of the available medications as a single agent until a response is achieved. However, the optimal sequence of medications is unknown. Furthermore, the value of combination therapy is not well defined. The rationale for using combination therapy is to use agents with non-overlapping toxicities to target different pathways involved in autoantibody production and platelet destruction. Considering that patients with refractory ITP have increased morbidity and mortality, an attractive hypothesis is whether early combination therapy using several active agents may increase response rates and shorten the time to response. If successful, this strategy may significantly decrease hospitalizations and bleeding.Another relatively unexplored area is the concept of medication tapering/discontinuation. Several of the medications used for the treatment of ITP have immunosuppressive properties or ...

A Case of Primary Refractory Immune Thrombocytopenia: Challenges in Choice of Therapies

“…The value of combination therapy for refractory ITP was not well defined. Immunosuppression therapies have been successfully added to rituximab [ 4 ] and TPO-RAs [ 5 , 6 ], respectively. Since rituximab has a relatively long time to response ( Table 1 ), TPO-RAs have been suggested as rational agents to combine with rituximab to induce a rapid increase in platelet counts.…”

Eltrombopag with i.v. immunoglobulin for safe splenectomy in refractory immune thrombocytopenia

“…Data are scarce with regard to the use of TPO‐R agonist combination therapy for refractory ITP. Recently, response to TPO‐R agonist combination therapy has been reported in some cases of adult ITP . TPO‐R agonists with IVIG may represent a possible therapeutic option for ITP refractory to second‐line treatment to increase platelet count and reduce the perioperative risk of bleeding during splenectomy or other surgical interventions.…”