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

Abstract

Promising reports of combination immunosuppression with high-dose dexamethasone and rituximab for the treatment of primary immune thrombocytopenia (ITP) have recently emerged. They suggest a potential to further optimize the efficacy of therapy. We investigate the use of a novel combination of conventional therapies in ITP given over 4 weeks. From 2011 to 2014, 20 patients were prospectively enrolled onto a single-arm phase 2b study to describe the safety, efficacy, and tolerability of oral dexamethasone 40 mg for days 1 to 4, oral cyclosporine 2.5 to 3 mg/kg daily for day 1 to 28, and intravenous low-dose rituximab 100 mg for days 7, 14, 21, and 28. There were no therapy-related serious adverse side effects, 6-month response rate was 60%, and treatment was well tolerated. Responders enjoyed relapse-free survivals of 92% and 76%, respectively, at 12 and 24 months. This study highlights the possibility of achieving an enduring remission from 4 weeks of therapy. This study is registered at www.anzctr.org.au (#ANZCTRN12611000015943).

© 2015 by The American Society of Hematology.

Figures

Figure 1

Platelet response, Kaplan Meier analyses and CD4+ lymphocyte depletion. (A) Whisker plots of platelet counts during the first 12 months from responders. The central horizontal bold line is the median; the cross is the mean; the lower and upper box limits are the first and third quartiles, respectively; and the whiskers include all data points. One patient relapsed at month 7. (B) Kaplan-Meier analysis of all patients treated with TT4. Vertical marks indicate the last follow-up of an ongoing response; 47% of the 20 treated patients were estimated to have a long-term response of >46 months from treatment. (C) Kaplan-Meier TFS curve for all patients. Median undefined, 75% treatment free at 12 months (95% CI, 49-88%). (D) Whisker plots of CD4+ T cells during the first 7 months: responders vs nonresponders. Median 0.62 vs 0.91 (P < .0001). The central horizontal line is the median; the lower and upper box limits are the first and third quartiles, respectively; and the whiskers include all data points. CD4+ counts were not significantly lower in men compared with women (P = .1639).