Researchers from Germany have reported that Torisel® (temsirolimus) improves progression-free survival (PFS) in patients with relapsed or refractory mantle cell lymphoma (MCL). The details of this Phase III study were published in the August, 2009 issue of the Journal of Clinical Oncology.[1]

Mantle cell lymphoma is a subset of non-Hodgkin’s lymphoma that is characterized by diffuse lymph node involvement, advanced stage of cancer at diagnosis, bone marrow involvement, and lymphoma cancer cells in the blood. More than half of patients with mantle cell lymphoma will respond to initial treatment, but the responses are typically short, and patients have an average survival of less than three years from diagnosis.

Many chemotherapy agents, and specifically Rituxan® (rituximab), have shown activity against MCL but have not improved overall average survival rates beyond three years. More recently, autologous and allogeneic stem cell transplants have emerged as a viable treatment option for these patients.

Torisel is a dihydroester of rapamycin that inhibits mTOR (mammalian target of rapamycin), a kinase enzyme. Treatment with Torisel leads to cell cycle arrest in the G1 phase and also inhibits angiogenesis by reducing synthesis of VEGF. Torisel is given intravenously and is undergoing Phase II-III testing in a variety of cancers. Currently, Torisel is only approved by the U.S. Food and Drug Administration for the treatment of renal cell carcinoma. Torisel has activity in patients with glioblastoma, breast cancer, and mantle cell lymphoma.

The Mayo Clinic and cooperating institutions reported outcomes of 35 patients with refractory MCL treated with Torisel 250 mg/week.[2] The median age for this group of patients was 70 years. Overall response rate was 35%, with one complete response. The median time to disease progression was 6.5 months. They reported that hematologic toxicities were the most frequent side effects.

A second study from the Mayo Clinic included 29 patients with relapsed or refractory MCL treated with a low-dose of Torisel (25 mg/week) for six to 12 weeks.[3] The overall response rate was 41% with one complete response. The median time to progression was six months, and the median duration of response was six months. These authors suggested that low-dose Torisel (25 mg/week) was as effective as the high dose (250 mg/week) with less hematological toxicity.

The current study included 162 patients with relapsed or refractory MCL, who were randomly allocated to treatment with one of two maintenance dose schedules of Torisel or to treatment chosen by the investigator. PFS was 4.8 months for patients receiving 175 mg of Torisel weekly for three weeks followed by 75 mg/week. PFS was 3.4 months for patients receiving 175 mg of Torisel weekly for three weeks followed by 25 mg/week. Patients in the control group had a PFS of 1.9 months. The response rate of patients receiving Torisel 175/75 mg/week was 22% compared with 2% in the control group. Median overall survival was 12.8 months for patients in the Torisel 175/75 mg/week group compared with 9.7 months in the control group. Side effects included thrombocytopenia, anemia, neutropenia, and asthenia.

Comments: These data confirm significant activity for Torisel for the treatment of patients with MCL.

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