Rituximab and three dexamethasone cycles provide responses similar to splenectomy in women and those with immune thrombocytopenia of less than two years duration

Abstract

Adults with newly diagnosed or persistent immunothrombocytopenia frequently relapse upon tapering steroids; adults and children with chronic disease have an even lower likelihood of lasting response. In adults with newlydiagnosed immunothrombocytopenia, two studies showed that dexamethasone 40 mg/day x four days and 4 rituximab infusions were superior to dexamethasone alone. Studies have also shown three cycles of dexamethasone are better than one and patients with persistent/chronic immunothrombocytopenia respond less well to either dexamethasone or rituximab. Therefore, 375 mg/m 2 x 4 rituximab was combined with three 4-day cycles of 28 mg/m 2 (max. 40 mg) dexamethasone at 2-week intervals and explored in 67 ITP patients. Best long-term response was assessed as complete (platelet count ≥100x10 9 /L) or partial (50-99x10 9 /L). Only 5 patients had not been previously treated. Fifty achieved complete (n=43, 64%) or partial (n=7, 10%) responses. Thirty-five of 50 responders maintained treatment-free platelet counts over 50x10 9 /L at a median 17 months (range 4-67) projecting 44% eventfree survival. Duration of immunothrombocytopenia less than 24 months, achieving complete responses, and being female were associated with better long-term response (P<0.01). Adverse events were generally mild-moderate, but 3 patients developed serum sickness and 2 colitis; there were no sequelae. Dexamethasone could be difficult to tolerate. Fourteen patients became hypogammaglobulinemic and half had increased frequency of minor infections; 9 of 12 evaluable patients recovered their IgG levels. Rituximab combined with three cycles of dexamethasone provides apparently better results to reported findings with rituximab alone, dexamethasone alone, or the combination with one cycle of dexamethasone. The results suggest medical cure may be achievable in immunothrombocytopenia, especially in women and in patients within two years of diagnosis. (clinicaltrials.gov identifier:02050581) Rituximab and three dexamethasone cycles provide responses similar to splenectomy in women and those with immune thrombocytopenia of less than two years duration

A novel triple therapy for ITP using high-dose dexamethasone, low-dose rituximab, and cyclosporine (TT4)

“…The improved outcome for men in our study has not been reported in studies previously using rituximab either alone 19 or in combination with dexamethasone. 10 Our study suggests that male ITP patients may benefit from T-cell suppression, but this requires confirmation by further studies.…”

“…7,8 Recent studies combining dexamethasone and rituximab in short courses have reported encouraging results. [9][10][11][12][13] We postulate that adding cyclosporine to this combination may induce a more enduring remission by also targeting T cells and thereby briefly suppressing all 3 immune cell types implicated in sustaining the pathogenic loop.…”

A multicenter randomized open-label study of rituximab plus rhTPO vs rituximab in corticosteroid-resistant or relapsed ITP

“…27,28 Later on, the combination of RTX and 3 cycles of dexamethasone showed apparently better efficacy than RTX alone or dexamethasone alone. 29 These conflicting findings indicate that the efficacy and safety of the combination of RTX with other drugs in the treatment of ITP needs further study. We hereby performed a multicenter prospective randomized controlled study in corticosteroid-resistant or relapsed ITP patients treated with either RTX 1 rhTPO or RTX alone, and we found that the combination yielded a significantly higher CR rate and shortened TTR compared with RTX alone but failed to show beneficial effect on the long-lasting response.…”

“…11,24,[29][30][31] In this study, the overall response rate in both groups was fairly high, which might be due to the generally short duration of ITP from diagnosis to enrollment. Age, gender, and the presence of autoantibodies were not associated with response rate or relapse in our study.…”

Splenectomy for immune thrombocytopenia: down but not out

“…82 However, a randomized study that enrolled corticosteroid-resistant ITP patients with a median ITP duration of 37 weeks failed to demonstrate a higher rate of long-term responses with rituximab. 83 Thus, whether rituximab is able to induce long-term remissions of ITP, or whether studies suggesting that it may do so reflect the natural history of the disease, remains unresolved.…”