Efficacy of Rituximab Combined in Salvage- and High Dose-Therapy (HDT) for Patients with Relapsed NHL; Interim Analysis of a Multicenter Phase II Study.

The introduction of Rituximab (R) in the treatment of B-NHL resulted in improvement in first line therapies for indolent (ind.) and aggressive (agg.) B-NHL. However, the value of R in intensive chemotherapy relapse strategies has not definitely been demonstrated. In a phase I/II clinical trial we have demonstrated safety of R as an in vivo purging agens in salvage and high dose therapy for relapsed/refractory B-NHL. This led, with promising response rates, to the initiation of a multicenter phase II trial to further prove therapeutic efficacy. Inclusion criteria were: Pt 1. rel. in 3 pts. 4 pts did not complete treatment due to death (1 sepsis, 1 unrelated reason) or mobil. failure (2), respectively. HDT (n=18 agg. NHL, 19 ind. NHL) could be performed without uncommon toxicities, one septic death occurred. In the agg. NHL group response to treatment in evaluated patients was CR in 14/18, PR in 2 and PD in 2. Corresponding figures for ind. NHL are CR in 18/19 and PR in 1/19 pts. With a median follow up of 20 months for patients undergoing HDT PFS and OS rates are 63% and 79% for agg. NHL and 65% and 100% for ind. NHL, respectively. In respect to historical data and in lack of randomized trials to test for the efficacy of R in HDT concepts, the result of this multicenter phase II study underlines the efficacy of this combined modality treatment approach in patients with chemosensitive disease. This seems to be favourable to prior experiences and probably reflects the benefit of the addition of R. However, as 1/4 of patients with agg. NHL still fail to respond to salvage therapy, the combination of R with intensive chemotherapy can not overcome chemoresistance in all patients, therefore defining a patient subgroup, for which more efficient strategies have to be developed.