Addition of the mammalian target of rapamycin inhibitor, everolimus, to consolidation therapy in acute myeloid leukemia: experience from the UK NCRI AML17 trial
Alan K Burnett,
Emma Das Gupta,
Steve Knapper,
Asim Khwaja,
Marion Sweeney,
Lars Kjeldsen,
Timothy Hawkins,
Sophie E Betteridge,
Paul Cahalin,
Richard E Clark,
Robert K Hills,
Nigel H Russell
Affiliations
Alan K Burnett
Formerly Department of Haematology, Cardiff University School of Medicine, UK
Emma Das Gupta
Department of Haematology, Nottingham University Hospital NHS Trust, UK
Steve Knapper
Department of Haematology, University Hospital of Wales, Cardiff, UK
Asim Khwaja
University College, London Cancer Institute, UK
Marion Sweeney
Department of Haematology, University Hospital of Wales, Cardiff, UK
Lars Kjeldsen
Department of Haematology, Rigshospitalet, Copenhagen, Denmark
Timothy Hawkins
Department of Haematology, Auckland City Hospital, New Zealand
Sophie E Betteridge
Centre for Trials Research, Cardiff University School of Medicine, UK
Paul Cahalin
Department of Haematology, Blackpool Victoria Hospital, UK
Richard E Clark
Department of Haematology, Royal Liverpool University Hospital, UK
Robert K Hills
Department of Haematology, Royal Liverpool University Hospital, UK
Nigel H Russell
Department of Haematology, Nottingham University Hospital NHS Trust, UK
As part of the UK NCRI AML17 trial, adult patients with acute myeloid leukemia in remission could be randomized to receive the mammalian target of rapamycin inhibitor everolimus, sequentially with post-induction chemotherapy. Three hundred and thirty-nine patients were randomised (2:1) to receive everolimus or not for a maximum of 84 days between chemotherapy courses. The primary endpoint was relapse-free survival. At 5 years there was no difference in relapse-free survival [29% versus 40%; odds ratio 1.19 (0.9-1.59) P=0.2], cumulative incidence of relapse [60% versus 54%: odds ratio 1.12 (0.82-1.52): P=0.5] or overall survival [45% versus 58%: odds ratio 1.3 (0.94-1.81): P=0.11]. The independent Data Monitoring Committee advised study termination after randomization of 339 of the intended 600 patients because of excess mortality in the everolimus arm without any evidence of beneficial disease control. The delivery of the everolimus dose was variable, but there was no evidence of clinical benefit in patients with adequate dose delivery compared with no treatment. This study suggests that the addition of mammalian target of rapamycin inhibition to chemotherapy provides no benefit.
