Intensified CHOP with Rituximab for Intermediate or High-Risk Non-Hodgkin’s Lymphoma: Interim Analysis of a Randomized Phase III Trial in Elderly Patients by the Dutch HOVON and Nordic Lymphoma Groups.

High-risk Non-Hodgkin lymphoma (NHL) in elderly patients (> 60 yrs) is associated with a relatively low complete response (CR) rate and a poor overall survival (OS). Previous studies have shown that addition of Rituximab to standard CHOP chemotherapy may improve CR and/or OS. A similar improvement has been shown for intensification of CHOP from 21 day intervals to 14 day intervals. The Dutch HOVON group and the Nordic lymphoma group have performed a multi-center, randomized phase III trial to compare 8 cycles of intensified CHOP (CHOP14) with the same regimen plus 6 administrations of Rituximab in previously untreated elderly patients with intermediate or high-risk NHL. Inclusion criteria were diffuse large B-cell lymphoma, mantle cell lymphoma or follicular lymphoma grade III; intermediate or high-risk NHL according to age adjusted IPI score; CD20-positive NHL; age 65 yrs or higher. The target number was 400 patients to be accrued in 5 years based on an expected increase in event-free survival with hazard ratio HR=0.70.

Aplanned interim analysis was performed after inclusion of 250 patients, restricted to 211 patients included from 1st September 2001 to 1st October 2004. Forty patients had to be excluded because of lack of treatment and evaluation data, leaving 171 patients for the analysis. The median time off protocol treatment was 119 days (range 4–468 days). The median age was 73 years (range 62–88 years). There was no difference between the two treatment arms regarding histology, age, WHO classification of NHL, age-adjusted IPI score, Ann Arbor stage, WHO performance status and serum LDH. There was no significant difference of toxicity or CR between the two treatment arms. However, a highly significant difference was observed for event-free survival and overall survival in favor of the treatment arm with CHOP plus Rituximab. Based on this interim analysis, the randomization was halted and patients in the control arm were further treated with CHOP plus Rituximab. Since the outcome of the interim analysis could be biased due to incomplete data, a final decision to stop the trial awaits a new analysis which is planned for 26th August 2005 after collection of missing or incomplete data. If the new analysis confirms the results of the interim analysis, i.e. that Rituximab significantly improves the outcome of treatment in elderly patients with intermediate or high-risk NHL, even when an intensified CHOP regimen is used, the study will be closed and outcomes will be presented.