Dexamethasone, rituximab combo improved response in adult ITP

50th ASH Annual Meeting

The combination of dexamethasone plus rituximab may be a safe and effective treatment option for patients with previously untreated idiopathic thrombocytopenic purpura, according to the results of a phase-3 study presented at the 50th Annual Meeting of the American Society of Hematology.

“The results of this study indicate that the addition of rituximab to dexamethasone improved the initial response, improved the sustained response rate and the active rescue of patients initially treated only with dexamethasone,” Francesco Zaja, MD, from the department of hematology DIRM, University of Udine, Italy, said during a press briefing on Saturday. “On the basis of these results we think that rituximab plus dexamethasone can be performed before splenectomy in patients that are refractory to steroids.”

One hundred one patients were randomly assigned to treatment with dexamethasone alone or dexamethasone plus rituximab (Rituxan, Genentech). The primary objective was to compare sustained response at six months between the two arms.

The researchers examined response in intent-to-treat and per-protocol populations.

Sixty-eight percent of patients in the intent-to-treat population and 85% of patients in the per-protocol population had a sustained response in the dexamethasone/rituximab arm compared with 36% of the intent-to-treat population and 39% of the per-protocol population assigned to dexamethasone alone.

Twenty-seven patients assigned to dexamethasone alone received salvage therapy with the combination treatment. Fifty-six percent of these patients had a sustained response.

Patients in the combination arm experienced an increase in any adverse events but not in serious adverse events (6% vs. 2%). – by Leah L. Lawrence

For more information:
Zaja F. #1. Presented at: 50^th Annual Meeting of the American Society of Hematology; December 5-9, 2008; San Francisco.

Over the past several years, numerous case reports and uncontrolled studies have suggested a beneficial effect of rituximab, an anti-CD20 monoclonal antibody, in patients with chronic ITP. However, information from controlled studies in adult ITP patients has been limited and most patients in published studies have been previously treated with other approaches. The study by Zaja and colleagues provides an important piece of information in this regard. They report the results of a prospective randomized trial comparing dexamethasone alone with a combination of rituximab plus dexamethasone in adult patients with chronic ITP. A particular strength of the study is that these patients were previously untreated. Both the initial response at 30 days and the sustained response at 6 months (platelet count of at least 50,000/uL) were impressively higher in patients receiving the two-drug regimen, which was well tolerated and associated with some longer-term remissions. This study extends the evidence regarding the beneficial effect of rituximab in chronic ITP. It is supported by convincing information from other studies that ITP patients have defective T-regulatory cell (Treg) mechanisms and that rituximab reverses these abnormalities. These lines of evidence and the burgeoning role of thrombopoiesis-stimulating agents lay the groundwork to rethink the current treatment algorithms in chronic ITP and design future trials to delineate the specific roles of these agents.

– A. Koneti Rao, MD

HemOnc Today Editorial Board member

The context of this study is an important one; practicing hematologists see many patients with ITP, many of whom are at significant risk for bleeding. Until now, dexamethasone or other glucocorticoids have been the standard of care, but they display many complications and are thus only used for short-term therapy. The addition of rituximab to glucocorticoids has been used in small case studies, but Dr. Zaja reported a randomized study in which the overall response rate was improved by adding rituximab, and the combination provided a prolonged response duration of therapy, compared to dexamethasone alone. I believe this represents an important advance, and is likely to change the way we treat patients with ITP.

– Kenneth Kaushansky, MD

President of the American Society of Hematology,

Helen M. Ranney Professor and Chair of the Department of Medicine,
University of California, San Diego School of Medicine