Supportive Efficacy Analyses for the Phase 3 Study of Temsirolimus Versus Investigator’s Choice Therapy for the Treatment of Patients with Relapsed or Refractory Mantle Cell Lymphoma.

Temsirolimus (Torisel®) is a specific inhibitor of the mTOR kinase with antitumor activity in patients with relapsed or refractory mantle cell lymphoma. In a phase 3, randomized, open-label study, patients treated with temsirolimus 175 mg weekly 3 times followed by 75 mg weekly (175/75-mg) had significantly longer progression-free survival (PFS) than those treated with investigator’s choice therapy (p-value temsirolimus: investigator’s choice = 0.0009; hazard ratio = 0.44; 97.5% CI = 0.25, 0.78;

1. evaluable population: those who remained on treatment for at least 8 weeks and did not discontinue early for PD or death, had no major protocol violations, and had at least 1 screening tumor assessment and at least 1 postbaseline independent tumor assessment to which an overall response was assigned

2. all deaths: those patients who had PD or died at any time during the study

3. all deaths + withdrawal from therapy + initiation of anticancer therapy: those patients who had PD, died, or stopped treatment because of withdrawal from therapy or initiation of other anticancer therapy; and

4. all deaths, excluding patients with blastoid histology. The latter analysis was performed because 0 patients in the 175/75-mg group and 4 patients in the investigator’s choice group had blastoid histology.

The characteristics of PFS for the 4 sensitivity analyses are shown (Table). In each analysis, PFS was significantly longer for the patients treated with temsirolimus 175/75-mg than for those treated with investigator’s choice therapy, consistent with the PFS results for the intent-to-treat population. Thus, based on several analyses, temsirolimus 175/75-mg benefits patients with relapsed or refractory mantle cell lymphoma. Additional exploratory analyses will be presented.