Low-dose, single-agent temsirolimus for relapsed mantle cell lymphoma: a phase 2 trial in the North Central Cancer Treatment Group

Cancer. 2008 Aug 1;113(3):508-14. doi: 10.1002/cncr.23580.


Background: The objective of this study was to test a low dose of (25 mg weekly) of the mammalian target of rapamycin kinase inhibitor temsirolimus for patients with relapsed mantle cell lymphoma (MCL).

Methods: Patients with relapsed or refractory MCL were eligible to receive temsirolimus 25 mg intravenously every week as a single agent. Patients who had a tumor response after 6 cycles were eligible to continue drug for a total of 12 cycles or 2 cycles after complete remission and then were observed without maintenance.

Results: Of 29 enrolled patients, 28 were evaluable for toxicity, and 27 were evaluable for efficacy. The median age was 69 years (range, 51-85 years), 86% of patients had stage IV disease, and 71% had > or = 2 extranodal sites. Patients had received a median of 4 prior therapies (range, 1-9 prior therapies), and 50% were refractory to the last treatment. The overall confirmed response rate was 41% (11 of 27 patients; 90% confidence interval [CI], 22%-61%) with 1 complete response (3.7%) and 10 partial responses (37%). The median time to progression in all eligible patients was 6 months (95% CI, 3-11 months), and the median duration of response for the 11 responders was 6 months (range, 1-26 months). Hematologic toxicities were the most common, with 50% (14 of 28 patients) grade 3 and 4% (1 of 28 patients) grade 4 toxicities observed. Thrombocytopenia was the most frequent cause of dose reduction.

Conclusions: Single-agent temsirolimus at a dose of 25 mg weekly is an effective new agent for the treatment of MCL. The 25-mg dose level retained the antitumor activity of the 250-mg dose with less myelosuppression. Further studies of temsirolimus in combination with other active drugs for MCL and other lymphoid malignancies are warranted.

Publication types

  • Clinical Trial, Phase II
  • Multicenter Study
  • Research Support, N.I.H., Extramural

MeSH terms

  • Aged
  • Aged, 80 and over
  • Antineoplastic Agents / administration & dosage
  • Antineoplastic Agents / adverse effects
  • Dose-Response Relationship, Drug
  • Drug Administration Routes
  • Drug Administration Schedule
  • Female
  • Humans
  • Lymphoma, Mantle-Cell / drug therapy*
  • Lymphoma, Mantle-Cell / mortality
  • Male
  • Middle Aged
  • Recurrence
  • Sirolimus / administration & dosage
  • Sirolimus / adverse effects
  • Sirolimus / analogs & derivatives*
  • Survival Analysis
  • Treatment Outcome
  • United States


  • Antineoplastic Agents
  • temsirolimus
  • Sirolimus