In:
British Journal of Haematology, Wiley, Vol. 175, No. 5 ( 2016-12), p. 917-924
Abstract:
The mammalian‐target of rapamycin (also termed mechanistic target of rapamycin, mTOR ) pathway integrates various pro‐proliferative and anti‐apoptotic stimuli and is involved in regulatory T‐cell ( TREG ) development. As these processes contribute to the pathogenesis of myelodysplastic syndromes ( MDS ), we hypothesized that mTOR modulation with temsirolimus ( TEM ) might show activity in MDS . This prospective multicentre trial enrolled lower and higher risk MDS patients, provided that they were transfusion‐dependent/neutropenic or relapsed/refractory to 5‐azacitidine, respectively. All patients received TEM at a weekly dose of 25 mg. Of the 9 lower‐ and 11 higher‐risk patients included, only 4 (20%) reached the response assessment after 4 months of treatment and showed stable disease without haematological improvement. The remaining patients discontinued TEM prematurely due to adverse events. Median overall survival ( OS ) was not reached in the lower‐risk group and 296 days in the higher‐risk group. We observed a significant decline of bone marrow ( BM ) vascularisation ( P = 0·006) but were unable to demonstrate a significant impact of TEM on the balance between TREG and pro‐inflammatory T‐helper‐cell subsets within the peripheral blood or BM . We conclude that mTOR ‐modulation with TEM at a dose of 25 mg per week is accompanied by considerable toxicity and has no beneficial effects in elderly MDS patients.
Type of Medium:
Online Resource
ISSN:
0007-1048
,
1365-2141
DOI:
10.1111/bjh.2016.175.issue-5
Language:
English
Publisher:
Wiley
Publication Date:
2016
detail.hit.zdb_id:
1475751-5