Randomized phase IV trial comparing efficacy and tolerability of temsirolimus with and without an elevated starting dose in patients with relapsed, refractory mantle cell lymphoma.

TPS222 Background: In a randomized phase III study (Hess et al. J Clin Oncol 2009;27:3822-9), patients with relapsed, refractory mantle cell lymphoma (MCL) who were treated with intravenous temsirolimus 175 mg for the first 3 weeks followed by 75 mg weekly (175/75) had significantly longer progression-free survival (PFS) compared with those receiving investigator’s choice of therapy (HR=0.44; P=.0009). The starting dose of 175 mg was, however, associated with a higher incidence of adverse events relative to investigator’s choice and to that observed with temsirolimus at lower doses. The aim of this study is to evaluate whether efficacy similar to that demonstrated in the phase III study can be achieved with better safety and tolerability in the absence of the 175-mg starting dose. A secondary objective is to assess the potential inhibitory effect of these doses of temsirolimus on cytochrome P450 2D6 substrate metabolism. Methods: Patients with relapsed, refractory MCL who received 2 to 7 prior therapies a...