Temsirolimus: In relapsed and/or refractory mantle cell lymphoma.

Temsirolimus selectively inhibits the mammalian target of rapamycin (mTOR) kinase, with subsequent inhibition of the translation of cell cycle regulatory proteins. Therapy with intravenous temsirolimus 175 mg once weekly for 3 weeks followed by 75 mg once weekly (higher temsirolimus dosage), but not 25 mg once weekly (lower temsirolimus dosage), was significantly more effective than single-agent chemotherapy of the investigator's choice in terms of the primary endpoint of progression-free survival (PFS), as assessed by independent review, in the treatment of adult patients with relapsed and/or refractory mantle cell lymphoma in a phase III study. Both dosage regimens of temsirolimus achieved significantly better outcomes with regard to PFS, as assessed by the investigator (secondary endpoint), than the investigator's choice therapy. Patients receiving the higher temsirolimus dosage achieved a significantly better outcome with regard to the objective response rate (ORR) than those receiving the investigator's choice therapy; however, no significant difference in terms of ORR was observed between patients receiving the lower temsirolimus dosage and those receiving the investigator's choice therapy. The differences between the two temsirolimus treatment groups and the investigator's choice treatment group with regard to the endpoint of overall survival did not reach statistical significance. The tolerability profile of temsirolimus in this patient population was mostly consistent with the known toxicities of the agent. The incidence of thrombocytopenia was significantly higher and that of leukopenia significantly lower in patients receiving the higher temsirolimus dosage compared with those receiving the investigator's choice therapy. Adverse events were often managed with dose modifications.