Temsirolimus and mantle cell lymphoma. Highly toxic, limited efficacy.

Mantle cell lymphoma is a highly malignant non-Hodgkin's lymphoma. There is no consensus on chemotherapy regimens for patients who do not qualify for haematopoietic stem cell transplantation. Temsirolimus, a metabolic precursor of sirolimus, already marketed in the European Union for metastatic kidney cancer, recently received an extension of indications to include relapsed or refractory mantle cell lymphoma. In this setting, one trial involving 162 patients in whom 2 or 3 chemotherapy regimens had failed compared two doses of temsirolimus (175 mg per week for 3 weeks, followed by 75 mg or 25 mg per week) versus a control group receiving various other treatments. The median overall survival time was about 11 months, regardless of the treatment.The median survival time before radiological or clinical progression was slightly longer with the higher dose of temsirolimus than in the control group (4.8 versus 1.9 months). Both of the temsirolimus dose regimens were highly toxic: 5 deaths, haematological disorders in more than 90% of patients, and haemorrhage or severe thrombocytopenia in about 50% of cases. Reactions during the infusion, infections, mucositis, fatigue and diarrhoea were also frequent.The cytochrome P450 isoenzyme CYP 3A4 is involved in temsirolimus metabolism, hence a high risk of pharmacokinetic interactions. The packaging is inappropriate and represents a potential source of dosing errors. In practice, temsirolimus shows only limited efficacy but is highly toxic in patients with relapsed or refractory mantle cell lymphoma after several prior chemotherapy regimens. It is better to avoid using this drug.