Randomized intergroup trial of first line treatment for patients <=60 years with diffuse large B-cell non-Hodgkin's lymphoma (DLBCL) with a CHOP-like regimen with or without the anti-CD20 antibody rituximab -early stopping after the first interim analysis

Abstract

6500 Background: While rituximab improved outcome in elderly patients with DLBCL (Coiffier et al., 2002), there is no data for young low-risk patients. Methods: In a randomized study conducted in 18 countries, untreated patients (18–60 years) with low-risk DLBCL (IPI 0 or 1, stages II-IV and stage I with bulk) were randomized to 6 cycles of a CHOP-like regimen (CHEMO) or the same chemotherapy plus rituximab 375 mg/m2 given on days 1, 22, 43, 64, 85, and 106 (R-CHEMO). Radiotherapy was planned to initial bulk and/or extranodal involvement. The primary endpoint was time to treatment failure (TTF) with events defined as failure to achieve complete remission, progressive disease, relapse, or death. The trial was powered to show a 10% difference in TTF rate after 3 years. Results: Between 05/2000 and 10/2003, 824 patients were recruited. The first planned interim analysis was performed on 326 evaluable patients with confirmed CD20 positive DLBCL (median age 48 years; IPI=1: 56%, 24% stage III/IV disease, 32% elevated LDH, 50% bulk). Toxicity was not different in the two arms. R-CHEMO patients had a significantly longer TTF (p=0.00003; log rank test) and overall survival (p=0.0057; log rank test) than CHEMO pateints. At a median observation time of 15 months, TTF rates were 84.0% for R-CHEMO and 62.5% for CHEMO. R-CHEMO patients had a higher complete remission rate (84.7% vs. 66.0%; p=0.0003) and a lower rate of progressive disease (6.3% vs. 17.7%; p=0.0039). As the empirical p-value of the log rank test statistic for TTF was considerably lower than the critical value for the interim analysis (pcrit=0.00105), the formal criterion for stopping the trial was met. Therefore, the DSMB recommended the early termination of the treatment phase of the trial in 12/2003 with 45/824 patients still under chemotherapy. Conclusions: The results of the MInT trial indicate that the addition of rituximab to 6 cycles of a CHOP-like regimen significantly improves TTF, CR rates, and OS in young patients with low-risk DLBCL. Author Disclosure Employment or Leadership Consultant or Advisory Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Roche, Basel (Switzerland) Roche, Basel (Switzerland)