A phase III study is the first to prospectively determine that adding Rituximab ( MabThera, Rituxan ) to Dexamethasone is safe and effective in adult patients with previously untreated idiopathic thrombocytopenic purpura ( ITP ). The results of this study indicated 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, the 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 and Rituximab ) in patients not responding to Dexamethasone alone, the identification of clinical and laboratory factors predictive of response, and the pharmacokinetic parameters of Rituximab 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 and Dexamethasone. The PP group included 38 patients treated with Dexamethasone alone and 26 treated with Rituximab and Dexamethasone.
ITT and PP sustained response rates were 63 percent and 85 percent in the Rituximab and Dexamethasone combination arm as compared with 36% and 39% 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% and 59%, respectively.
No clinical or laboratory factors predictive of a sustained response were identified in the study. There was 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 ). ( Xagena )
Source: American Society of Hematology, 2008