Rituximab efficacy and safety in adult splenectomy candidates with chronic immune thrombocytopenic purpura: results of a prospective multicenter phase 2 study

Abstract

IntroductionImmune thrombocytopenic purpura (ITP) is an autoimmune disease characterized by low platelet counts and may be responsible for mucocutaneous bleeding of variable severity. 1 ITP is usually chronic (Ͼ 6 months) in adults and, after this time, the probability of spontaneous remission is low. Standard management is to initiate steroids, anti-Rh 0 (D) immune globulins, and/or intravenous immunoglobulins (IVIgs) for the more severe forms. [2][3][4][5] The response rate is high but most often transient. That the spleen plays a major role in the removal of damaged platelets has long been known and, to date, splenectomy is still considered the "gold standard" treatment in many countries for the management of chronic ITP with platelet counts less than 30 ϫ 10 9 /L, especially when hemorrhagic complications are present. Approximately two thirds of chronic ITP patients who undergo splenectomy achieve lasting responses. 6 As suggested in the guidelines of the American Society of Hematology (ASH) 7 and the British Committee for Standards in Hematology (BCSH), 8 splenectomy should be considered the main second-line therapy for patients who fail to respond durably to first-line therapy, with persistent platelet counts less than 30 ϫ 10 9 /L. However, increasing numbers of patients are reluctant to undergo splenectomy and physicians are hesitant to recommend it. 9,10 In addition, the risk of overwhelming postsplenectomy infections, although rare, is not predictable and represents a major concern. 11-13 Moreover, some authors reported that, despite initial good responses to splenectomy, the risk of late relapse persists during long-term follow-up 14,15 and severe morbidity resulting from surgery is associated with 11% to 30% postoperative complications requiring prolonged hospitalization or readmission. 11,16 For these reasons, an effective and safe alternative to splenectomy would improve management of chronic ITP.Rituximab is a chimeric, humanized monoclonal antibody directed against the CD20 determinant on B cells. It was initially developed for the treatment of malignant lymphoma but has also been used in autoantibody-mediated disorders, such as rheumatoid arthritis, 17 systemic lupus erythematosus, 18 autoimmune hemolytic anemia, 19 or thrombotic thrombocytopenic purpura. 20 Case reports and several uncontrolled studies described its promising results in ITP patients. Arnold et al 21 conducted a systematic review of published reports on rituximab use in adults with chronic ITP. A complete response, usually observed 3 to 8 weeks after the first infusion, was obtained in 46% of patients. The median response duration was 10.5 months (interquartile range [IQR]: 6.3-17.8 months), but long-term For personal use only. on May 10, 2018. by guest www.bloodjournal.org From responses were not mentioned in all published studies. Arnold et al 21 pointed out the heterogeneity of patients' prior rituximab use and particularly their splenectomy status. Moreover, the short follow-up in some reports and the possible bias due to th...

Long‐term follow‐up analysis after rituximab salvage therapy in adult patients with immune thrombocytopenia

“…This discrepancy could be at least partially explained by ours and Godeau's selection of patients with a lower degree of treatments received before rituximab [19].…”

“…The effect of rituximab to safely avoid splenectomy has been also prospectively investigated by Godeau et al [19] in 60 adults with chronic ITP. The authors indicated that, at 2 years, 24 (40%) patients responded to rituximab (i.e., platelet counts 30 3 10 9 /L or more off treatment) avoiding splenectomy.…”

Subcutaneous immunoglobulin in lymphoproliferative disorders and rituximab-related secondary hypogammaglobulinemia: a single-center experience in 61 patients

“…It is important to report that even in these few patients the use of SCIg was effective, safe and well tolerated. The use of the anti-CD20 monoclonal antibody rituximab is expanding in several autoimmune disorders, including rheumatoid arthritis, [31][32][33] immune thrombocy-topenic purpura, 34,35 systemic lupus erythematosus, 36 Sjogren syndrome, anti-neutrophil cytoplasmic antibodyassociated vasculitis, mixed cryoglobulinemia, solid organ transplantation, renal disease, and neurological diseases. 37 Thus, in our Clinical Immunology Unit, a further study is in progress on the putative role of SCIg in the prevention of hypogammaglobulinemia-related infections in nonneoplastic conditions after rituximab therapy.…”

Efficacy and safety of rituximab given at 1,000 mg on days 1 and 15 compared to the standard regimen to treat adult immune thrombocytopenia

“…In immune thrombocytopenia (ITP), B-cell depletion using the lymphoma-type regimen (i.e., at the standard dose, namely 375 mg/m 2 weekly for 4 weeks), is now a second-line off-label therapy in many countries and is used prior to splenectomy, or as a third-line therapy for patients not responding to a splenectomy [3]. In France, based on the findings of a single-arm prospective study [4], RTX is now commonly used in persistent or chronic cases of adult ITP prior to splenectomy. Approximately 40-50% of patients treated with RTX at a standard dose achieve a complete response (CR) by 1 year [5] and 20% have a lasting response at 5 years [6].…”