Triple treatment option

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).

Submitted March 3, 2015.
Accepted May 11, 2015.

© 2015 by The American Society of Hematology

www.bloodjournal.org/content/126/4/500.abstract?ct=

Nice find. Full text of the article is freely available on the "Blood Journal" web site. I read through the article once, and though I've still got to look up some things and see if I can find their "Data Supplement," the results are promising. Combination therapies are becoming more common in oncology in general, and the trick seems to be finding the precise combination of agents and protocols to get maximize the benefits with respect to side effects and risks.

I'd like to see them do a broader trial that more fully characterizes the ITP patient pool as well as giving longer-term outcomes.

These cocktails seem to have pretty good results for remissions. I'd much rather go through this first than go through a year of other failed treatments and then try this. Would definitely cut down on toxicities.

I saw an earlier version of this when it came out in March. I am still unimpressed. You have to be very careful when they talk of "% of responders"

When the article refers to 92% enjoyed relapse free survival at 12 months they are referring only to the responders. The 6 month response rate was 60% (12/20), and 92% (11/12) of them - 55% of the total, or 11/20 - were treatment-free after a year. Similarly, 45% or 9/20, were treatment free after 24 months.

These results appear comparable to studies I have seen on low-dose Rituxan alone. They nearly match the results from one of the Zaja studies:

Low-dose rituximab in adult patients with primary immune thrombocytopenia.
Zaja F, et al Eur J Haematol. 2010 Oct
www.ncbi.nlm.nih.gov/pubmed/20546023
Results: Overall and complete responses (CR) (platelet level ≥ 50 and 100 × 10(9) /L) were 60.5% and 39.5%, respectively. In responders, the median time to response was 35 d (range: 7-112 d). The median time of observation was 18 months (range 3-49 months). Sixteen of 29 responding patients (55%) relapsed and 14 needed further treatments. The 12- and 24-month cumulative relapse-free survival was 61% and 45%, respectively. In univariate analysis, CR rate was in inverse relation with weight OR=0.95, CI(95%) [0.91; 0.99] (P=0.019) and age OR=0.96, CI(95%) [0.93; 0.99] (P=0.047). Cox regression model showed that relapse probability increases as weight (HR=1.06, CI(95%) [1.0031; 1.111]) and period between diagnosis and rituximab therapy (HR=1.01, CI(95%) [1.002; 1.017]) increase. One patient developed an interstitial pneumonia 1 month after the end of rituximab treatment. No other infectious, hematologic or extra-hematologic complications were documented during follow-up.