Results from a multicenter phase III study conducted by a team of researchers from Clinica Ematologica DIRM AOUD, Udine, Italy, were presented by Francesco Zaja, MD.This study is the first trial to prospectively determine that adding the immunotherapy drug rituximab, an anti-CD20 monoclonal antibody, to dexamethasone, a steroid that is a standard therapy for idiopathic thrombocytopenic purpura (ITP), is safe and effective in adult patients with previously untreated ITP, an autoimmune disorder characterized by low platelet counts. Primary ITP, which typically occurs in an otherwise healthy individuals, has an unknown etiology.
After analyzing the data, the researchers concluded that this treatment regimen could be an effective option prior to splenectomy for some patients as well as a possible cure for others.In this study, patients were randomized to one of two treatment regimens: oral dexamethasone alone (40 mg) given on the first four days of treatment or the same regimen of dexamethasone plus rituximab given as an intravenous infusion (375 mg/m2) once a week for four weeks. Some patients in the dexamethasone-only arm who failed to achieve a sustained response and had platelet counts of less than or equal to 20 x 109/L following 30 days of therapy up to the end of six months received a salvage (rescue) treatment of rituximab plus dexamethasone.
The primary objective of the study was to compare the sustained response (platelet counts greater than or equal to 50 x 109/L from one month to six months from the beginning of therapy) between the two treatment groups. Secondary objectives included overall safety, initial response (platelet count of 50 x 109/L after 30 days of treatment), activity of the salvage therapy (dexamethasone/rituximab) in patients not responding to dexamethasone alone, the identification of clinical and laboratory factors predictive of response, and the pharmacokinetic parameters of rituximab (the level of ritixumab circulating in the blood of patients during the study period) and their potential relation to response.
The researchers examined the results for all enrolled patients, regardless of whether or not they completed the study (intention-to-treat basis, ITT), and on a per-protocol (PP) basis, examining those who had completed the treatment regimen. The ITT group included 52 patients treated with dexamethasone alone and 49 treated with rituximab/dexamethasone. The PP group included 38 patients treated with dexamethasone alone and 26 treated with rituximab/dexamethasone. ITT and PP sustained response rates were 63 percent and 85 percent in the rituximab/dexamethasone combination arm as compared with 36 percent and 39 percent in the dexamethasone-alone arm.
A total of 27 patients who failed to achieve an initial or sustained response in the dexamethasone-alone arm received the salvage treatment. In this group, ITT and PP sustained response rates were 56 percent and 59 percent, respectively.While were no clinical or laboratory factors predictive of a sustained response identified in the study, the researchers did report a mild increase in the incidence of severe adverse events in the dexamethasone-plus-rituximab arm (2 percent in dexamethasone arm versus 6 percent in dexamethasone-plus-rituximab arm).
Last editorial review: December 9, 2008.
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