Effect of prognostic classification on temsirolimus efficacy and safety in patients with relapsed or refractory mantle cell lymphoma: a retrospective analysis

Abstract

Background: Temsirolimus, a selective inhibitor of the mammalian target of rapamycin, has demonstrated clinical benefit versus investigator's choice (INV) of therapy in patients with relapsed/refractory mantle cell lymphoma (MCL).

Methods: This post hoc study retrospectively assigned simplified Mantle Cell Lymphoma International Prognostic Index (MIPI) scores (ie, secondary MIPI) based on parameters at the time of randomization in patients with MCL (N = 162) who received temsirolimus 175 mg once weekly for 3 weeks followed by once-weekly 75 mg or 25 mg or the INV of active therapy. Outcomes were analyzed according to the low-, intermediate- or high-risk category.

Results: Patient distribution by MIPI risk category was 31%, 39%, and 30% in the low-, intermediate-, and high-risk groups, respectively. Among patients in all categories, objective response rate (complete response + partial response) was higher in patients in the temsirolimus 175/75-mg group versus the INV group, respectively: 42% versus 0% (low-risk); 33% versus 5% (intermediate-risk); 10% versus 0% (high-risk). Median progression-free survival was significantly longer with temsirolimus 175/75 mg versus INV, respectively, in patients with intermediate (4.3 vs 1.9 months; P = 0.035) or high (4.5 vs 1.6 months; P = 0.0025) risk, and a trend toward improvement was observed in patients with low risk (5.3 vs 2.6 months; P = 0.091). Improvement in median overall survival was observed with temsirolimus 175/75 mg versus INV in low-risk patients (18.0 vs 10.5 months, respectively; P = 0.069).

Conclusions: This analysis suggests that, compared with INV, temsirolimus demonstrated benefit in all MIPI risk categories in patients with MCL. In all treatment groups, patients with high secondary MIPI scores at baseline faced a dismal prognosis.

Trial registration: ClinicalTrials.gov NCT00117598.

Keywords: Efficacy; Mantle cell lymphoma; Prognostic; Risk; Safety; Temsirolimus.

Figures

Figure 1

Kaplan-Meier plots of progression-free survival by MIPI risk group. (A) Low-risk group, (B) intermediate-risk group, and (C) high-risk group. Log-rank P values given for temsirolimus versus investigator’s choice of therapy. Statistical analyses shown are for illustrative purposes; the phase III trial was not powered to detect differences in progression-free survival for subsets by MIPI risk categories. MIPI = Mantle Cell Lymphoma International Prognostic Index; TEMSR 25 mg = temsirolimus 25 mg administered once weekly after three weekly doses of 175 mg; TEMSR 75 mg = temsirolimus 75 mg administered once weekly after three weekly doses of 175 mg.