The mammalian target of rapamycin (mTOR) signalling pathway has emerged as an important therapeutic target for acute myeloid leukaemia (AML). This study assessed the combination of temsirolimus, an mTOR inhibitor, and lower-dose clofarabine as salvage therapy in older patients with AML. Induction consisted of clofarabine 20mg/m(2) on days 1-5 and temsirolimus 25mg (flat dose) on days 1, 8 and 15. Patients achieving complete remission with (CR) or without (CRi) full haematological recovery could receive monthly temsirolimus maintenance. In 53 evaluable patients, the overall remission rate (ORR) was 21% (8% CR, 13% CRi). Median disease-free survival was 3·5months, and median overall survival was 4months (9·1months for responders). The most common non-haematological severe adverse events included infection (48%), febrile neutropenia (34%) and transaminitis (11%). The 30-d all-cause induction mortality was 13%. Laboratory data from 25 patients demonstrated that a >50%in vivo inhibition of S6 ribosomal protein phosphorylation was highly correlated with response rate (75% with inhibition versus 0% without inhibition; P=0·0001), suggesting that targeting the mTOR pathway is clinically relevant. The acceptable safety profile and the predictive value of target inhibition encourage further investigation of this novel regimen.

Amadori, S., Stasi, R., Martelli, A., Venditti, A., Meloni, G., Pane, F., Martinelli, G., Lunghi, M., Pagano, L., Cilloni, D., Rossetti, E., Di Raimondo, F., Fozza, C., Annino, L., Chiarini, F., Ricci, F., Ammatuna, E., La Sala, E., Fazi, P., Vignetti, M., Temsirolimus, an mTOR inhibitor, in combination with lower-dose clofarabine as salvage therapy for older patients with acute myeloid leukaemia: results of a phase II GIMEMA study (AML-1107), <<BRITISH JOURNAL OF HAEMATOLOGY>>, 2012; 156 (2): 205-212. [doi:10.1111/j.1365-2141.2011.08940.x] [http://hdl.handle.net/10807/3843]

Temsirolimus, an mTOR inhibitor, in combination with lower-dose clofarabine as salvage therapy for older patients with acute myeloid leukaemia: results of a phase II GIMEMA study (AML-1107)

Venditti, Antonella;Pagano, Livio;Ricci, Francesco;
2012

Abstract

The mammalian target of rapamycin (mTOR) signalling pathway has emerged as an important therapeutic target for acute myeloid leukaemia (AML). This study assessed the combination of temsirolimus, an mTOR inhibitor, and lower-dose clofarabine as salvage therapy in older patients with AML. Induction consisted of clofarabine 20mg/m(2) on days 1-5 and temsirolimus 25mg (flat dose) on days 1, 8 and 15. Patients achieving complete remission with (CR) or without (CRi) full haematological recovery could receive monthly temsirolimus maintenance. In 53 evaluable patients, the overall remission rate (ORR) was 21% (8% CR, 13% CRi). Median disease-free survival was 3·5months, and median overall survival was 4months (9·1months for responders). The most common non-haematological severe adverse events included infection (48%), febrile neutropenia (34%) and transaminitis (11%). The 30-d all-cause induction mortality was 13%. Laboratory data from 25 patients demonstrated that a >50%in vivo inhibition of S6 ribosomal protein phosphorylation was highly correlated with response rate (75% with inhibition versus 0% without inhibition; P=0·0001), suggesting that targeting the mTOR pathway is clinically relevant. The acceptable safety profile and the predictive value of target inhibition encourage further investigation of this novel regimen.
2012
Inglese
Amadori, S., Stasi, R., Martelli, A., Venditti, A., Meloni, G., Pane, F., Martinelli, G., Lunghi, M., Pagano, L., Cilloni, D., Rossetti, E., Di Raimondo, F., Fozza, C., Annino, L., Chiarini, F., Ricci, F., Ammatuna, E., La Sala, E., Fazi, P., Vignetti, M., Temsirolimus, an mTOR inhibitor, in combination with lower-dose clofarabine as salvage therapy for older patients with acute myeloid leukaemia: results of a phase II GIMEMA study (AML-1107), <<BRITISH JOURNAL OF HAEMATOLOGY>>, 2012; 156 (2): 205-212. [doi:10.1111/j.1365-2141.2011.08940.x] [http://hdl.handle.net/10807/3843]
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/10807/3843
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