Phase III study to evaluate temsirolimus compared with investigator's choice therapy for the treatment of relapsed or refractory mantle cell lymphoma.

Temsirolimus, a specific inhibitor of the mammalian target of rapamycin kinase, has shown clinical activity in mantle cell lymphoma (MCL). We evaluated two dose regimens of temsirolimus in comparison with investigator's choice single-agent therapy in relapsed or refractory disease. In this multicenter, open-label, phase III study, 162 patients with relapsed or refractory MCL were randomly assigned (1:1:1) to receive one of two temsirolimus regimens: 175 mg weekly for 3 weeks followed by either 75 mg (175/75-mg) or 25 mg (175/25-mg) weekly, or investigator's choice therapy from prospectively approved options. The primary end point was progression-free survival (PFS) by independent assessment. Median PFS was 4.8, 3.4, and 1.9 months for the temsirolimus 175/75-mg, 175/25-mg, and investigator's choice groups, respectively. Patients treated with temsirolimus 175/75-mg had significantly longer PFS than those treated with investigator's choice therapy (P = .0009; hazard ratio = 0.44); those treated with temsirolimus 175/25-mg showed a trend toward longer PFS (P = .0618; hazard ratio = 0.65). Objective response rate was significantly higher in the 175/75-mg group (22%) compared with the investigator's choice group (2%; P = .0019). Median overall survival for the temsirolimus 175/75-mg group and the investigator's choice group was 12.8 months and 9.7 months, respectively (P = .3519). The most frequent grade 3 or 4 adverse events in the temsirolimus groups were thrombocytopenia, anemia, neutropenia, and asthenia. Temsirolimus 175 mg weekly for 3 weeks followed by 75 mg weekly significantly improved PFS and objective response rate compared with investigator's choice therapy in patients with relapsed or refractory MCL.