News

ASH 2010: Temsirolimus for the treatment of advanced acute myeloid leukaemia

10 Dec 2010

Elderly patients with refractory or relapsed acute myeloid leukaemia (AML) have a dismal prognosis and new treatments are needed for these patients. The PI3K/AKT signalling pathway is frequently dysregulated in AML and contributes to cell proliferation and survival through activation of the mTOR kinase and its downstream effectors.

mTOR inhibition with sirolimus or its analogs, such as temsirolimus, has been associated with clinical responses in AML and may enhance the sensitivity of leukaemic cells to cytotoxics. Clofarabine is a second-generation nucleoside analog with activity in AML.

A multicentre, Phase 2, open label, two-stage study was conducted to assess the efficacy and safety of temsirolimus in combination with low-dose clofarabine as salvage therapy for older patients with AML. In an interim analysis of 52 patients, 11 (21%) achieved a complete response (n=4) or response with incomplete platelet recovery (n=7), with a median duration of remission of 3.5 months. In contrast to this, 33 patients were resistant to treatment. The median overall survival for the entire population was 4.3 months, and for responders was 7.6 months.

Adverse events were typical of those seen with these treatments. It was concluded that a regimen combining temsirolimus with low-dose clofarabine could be safely administered to elderly patients with advanced AML. Encouraging anti-leukaemic activity was recorded in this difficult-to-treat patient population, particularly in patients showing evidence of an on-target effect on mTOR signalling.

Further investigation of this novel regimen as front-line therapy in older patients with AML considered unsuitable for intensive chemotherapy is planned.

Reference

S Amadori, A Venditti, E Ammatuna et al Temsirolimus, An mTOR Inhibitor, In Combination with Low-Dose Clofarabine in Older Patients with Advanced Acute Myeloid Leukemia: Results of a Phase 2 GIMEMA Study (AML-1107) Abstract 510 presented at 52nd ASH, Orlando, FL, December 4-7, 2010