Comparison of two doses of intravenous temsirolimus in patients with relapsed/refractory mantle cell lymphoma.

Temsirolimus 175mg once-weekly for 3 weeks, followed by 75mg once-weekly intravenously dosed (175/75mg) is approved in the European Union for treatment of relapsed/refractory mantle cell lymphoma (MCL). A phase IV study explored whether similar efficacy, but improved safety could be achieved with 75mg without 175mg loading doses (ClinicaTrials.gov: NCT01180049). Patients with relapsed/refractory MCL were randomized to once-weekly temsirolimus 175/75mg (n=47) or 75mg (n=42). Treatment continued until objective disease progression. Primary endpoint: progression-free survival (PFS). Secondary endpoints included overall survival (OS) and adverse events (AEs). Median PFS was 4.3 versus 4.5 months (hazard ratio [HR] 0.731; 80% confidence interval [CI], 0.520-1.027), and median OS 18.7 versus 11.0 months (HR 0.681; 80% CI, 0.472-0.982) with 175/75mg versus 75mg. There were fewer patients with serious AEs, dose reduction, or death with 175/75mg (57.4%, 48.9%, and 48.9%) versus 75mg (73.8%, 64.3%, and 65.1%). Temsirolimus 175/75mg remains the preferred dosing regimen for relapsed/refractory MCL.