NIGEL RUSSELL (NOTTINGHAM)
NUCLEOSIDE ANALOGUES IN HIGH-RISK AML
Nottingham University Hospital, Nottingham, United Kingdom
Gradual but definite progress has been made in the treatment of younger adults with acute myeloid
leukaemia (AML) but less so in the 30% with high-risk disease. For them the best approach is an
allogeneic transplant (SCT). These patients represent an important unmet therapeutic need for
which there is no specific standard of care. The challenge is three-fold. First, for those who will go
forward to transplant improving the pre-transplant chemotherapy could reduce the post-transplant
relapse rate. Second, better treatment could deliver more patients to transplant who otherwise
might relapse before reaching transplant. Third, better treatment is needed for patients for whom a
transplant is not available.
For relapsed patients the FLAG-Ida (fludarabine/cytosine arabinoside (ara-C)/granulocyte-colony
stimulating factor (G-CSF) and idarubicin) is widely used. In our MRC AML15 Trial, FLAG-Ida given for
the first two treatment courses had a significantly superior anti-leukaemia effect. It therefore
appeared logical to continue with FLAG-Ida as consolidation for patients who were identified as high
risk. We chose as the comparative treatment Clofarabine to replace Ara-C, in a daunorubicin/Ara-C
combination. Clofarabine has demonstrated activity in adverse risk patients and recent studies have
shown a benefit for clofarabine combined with araC in consolidation or by its addition to DA in
induction where it improved EFS but not OS.
In our AML17 trial, 311 patients were randomised after having received the first induction course
consisting of chemotherapy was DA+GO or DA+/- etoposide or DA90. The patients were designated
as high risk by our validated weighted score (based on cytogenetics, gender, white count, secondary
disease, older age, and failure to achieve at least a reduction in marrow blasts to <15%, or to 50% of
blasts at diagnosis). Overall 84% of high-risk patients achieved CR or CRi as the best response with no
differences between the arms. The artes of MRD negativity was higher in the FLAG-Ida arm.
Although FLAG-Ida did not deliver more patients to SCT, OS was significantly better than with DClo,
partly because of the better relapse free survival after transplant (69% vs. 39%). This study
concluded that the FLAG-Ida was superior in high-risk patients, despite not delivering more patients
to transplant than the clofarabine regimen.
Reference. Burnett, A. K., Hills, R. K., Nielsen, O. J., Freeman, S., Ali, A., Cahalin, P., Hunter, A., Thomas, I. F., &
Russell, N. H. (2018). A comparison of FLAG-Ida and daunorubicin combined with clofarabine in high-risk acute
myeloid leukaemia: data from the UK NCRI AML17 Trial. Leukemia, 32(12), 2693–2697.
SCIENTIFIC
PROGRAMME
RARE SUBSETS OF
ACUTE LEUKAEMIA
TRACKING LEUKAEMIC
STEM CELLS (LSCs)
ROUTINE DIAGNOSIS
GENE EXPRESSION
AND MUTATIONAL
PROFILING
DEBATE 1 – ALL
PATIENTS WITH
INTERMEDIATE-RISK
AML MUST BE
TRANSPLANTED
INTERACTIVE
CASES 1 – MUTATION-BASED
THERAPY
OFF-LABEL
ROUNDTABLE –
SHOULD WE REALLY
USE NEW TARGETED
INHIBITORS AS SINGLE
AGENTS ?
ADDITION OF A 3RD
AGENT TO FRONTLINE
7+3
ROUNDTABLE –
CURATIVE OPTIONS
FOR OLDER AML
INTERACTIVE CASES 2
DEBATE 2 - BEST
TREATMENT FOR
NPM1-MUTATED AML IN
THE NEXT FUTURE ?
ALLOGENEIC
HAEMATOPOIETIC
STEM CELL
TRANSPLANTATION
(HSCT)
IMMUNOTHERAPY FOR
ACUTE LEUKAEMIA
DEBATE 3 - T-ALL:
WHERE ARE WE GOING
NOW?
SELECTED ABSTRACTS
AND CLINICAL
CASES FOR AN ORAL
PRESENTATION
SELECTED ABSTRACTS
FOR A POSTER
PRESENTATION
DISCLOSURES