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.
| Original language | English |
|---|---|
| Pages (from-to) | 205-212 |
| Number of pages | 8 |
| Journal | British Journal of Haematology |
| Volume | 156 |
| Issue number | 2 |
| DOIs | |
| Publication status | Published - Jan 2012 |
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Keywords
- Acute myeloid leukaemia
- Clofarabine
- Elderly patients
- Mammalian target of rapamycin
- Temsirolimus
ASJC Scopus subject areas
- Hematology
Cite this
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). / Amadori, Sergio; Stasi, Roberto; Martelli, Alberto M.; Venditti, Adriano; Meloni, Giovanna; Pane, Fabrizio; Martinelli, Giovanni; Lunghi, Monia; Pagano, Livio; Cilloni, Daniela; Rossetti, Elena; Di Raimondo, Francesco; Fozza, Claudio; Annino, Luciana; Chiarini, Francesca; Ricci, Francesca; Ammatuna, Emanuele; La Sala, Edoardo; Fazi, Paola; Vignetti, Marco.
In: British Journal of Haematology, Vol. 156, No. 2, 01.2012, p. 205-212.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Temsirolimus, an mTOR inhibitor, in combination with lower-dose clofarabine as salvage therapy for older patients with acute myeloid leukaemia
T2 - Results of a phase II GIMEMA study (AML-1107)
AU - Amadori, Sergio
AU - Stasi, Roberto
AU - Martelli, Alberto M.
AU - Venditti, Adriano
AU - Meloni, Giovanna
AU - Pane, Fabrizio
AU - Martinelli, Giovanni
AU - Lunghi, Monia
AU - Pagano, Livio
AU - Cilloni, Daniela
AU - Rossetti, Elena
AU - Di Raimondo, Francesco
AU - Fozza, Claudio
AU - Annino, Luciana
AU - Chiarini, Francesca
AU - Ricci, Francesca
AU - Ammatuna, Emanuele
AU - La Sala, Edoardo
AU - Fazi, Paola
AU - Vignetti, Marco
PY - 2012/1
Y1 - 2012/1
N2 - 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.
AB - 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.
KW - Acute myeloid leukaemia
KW - Clofarabine
KW - Elderly patients
KW - Mammalian target of rapamycin
KW - Temsirolimus
UR - http://www.scopus.com/inward/record.url?scp=84155180788&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84155180788&partnerID=8YFLogxK
U2 - 10.1111/j.1365-2141.2011.08940.x
DO - 10.1111/j.1365-2141.2011.08940.x
M3 - Article
VL - 156
SP - 205
EP - 212
JO - British Journal of Haematology
JF - British Journal of Haematology
SN - 0007-1048
IS - 2
ER -