Prognostic relevance of treatment response measured by flow cytometric residual disease detection in older patients with acute myeloid leukemia.
OBJECTIVE
Older patients with acute myeloid leukemia (AML) have a high relapse rate after standard chemotherapy. We investigated whether measuring chemotherapy sensitivity by multiparameter flow cytometric minimal residual disease (MFC-MRD) detection has prognostic value in patients older than age 60 years or is simply a surrogate for known age-related risk factors.


METHODS
Eight hundred ninety-two unselected patients treated intensively in the United Kingdom National Cancer Research Institute AML16 Trial were assessed prospectively for MFC-MRD during treatment. Eight hundred thirty-three patients had leukemia-associated immunophenotypes (LAIPs) identified by pretreatment screening. Four hundred twenty-seven patients entered complete remission (CR) after one or two courses (designated C1 and C2, respectively) and were MFC-MRD assessable by LAIP detection in CR bone marrow for at least one of these time points. MRD positivity was defined as residual disease detectable by LAIP.


RESULTS
MFC-MRD negativity, which was achieved in 51% of patients after C1 (n = 286) and 64% of patients after C2 (n = 279), conferred significantly better 3-year survival from CR (C1: 42% v 26% in MRD-positive patients, P < .001; C2: 38% v 18%, respectively; P < .001) and reduced relapse (C1: 71% v 83% in MRD-positive patients, P < .001; C2: 79% v 91%, respectively; P < .001), with higher risk of early relapse in MRD-positive patients (median time to relapse, 8.5 v 17.1 months, respectively). In multivariable analysis, MRD status at the post-C1 time point independently predicted survival, identifying a subgroup of intermediate-risk patients with particularly poor outcome. However, survival benefit from gemtuzumab ozogamicin was not associated with MFC-MRD chemotherapy sensitivity.


CONCLUSIONS
Early assessment of treatment response using flow cytometry provides powerful independent prognostic information in older adults with AML, lending support to the incorporation of MRD detection to refine risk stratification and inform clinical trial design in this challenging group of patients.
Sylvie D. Freeman, University of Birmingham and University Hospitals Birmingham National Health Service (NHS) Trust, Birmingham; Paul Virgo, North Bristol NHS Trust, Bristol; Steve Couzens, University Hospital of Wales; Robert K. Hills and Alan K. Burnett, Cardiff University, Heath Park, Cardiff; David Grimwade, King's College London School of Medicine and Guy's and St Thomas' NHS Foundation Trust, London; and Nigel Russell, Nottingham University Hospital NHS Trust, Nottingham, United Kingdom.
Sylvie D
SD
Freeman
Paul
P
Virgo
Steve
S
Couzens
David
D
Grimwade
Nigel
N
Russell
Robert K
RK
Hills
Alan K
AK
Burnett
D000368:Aged; D000369:Aged, 80 and over; D000617:Aminoglycosides / Q000627:therapeutic use; D061067:Antibodies, Monoclonal, Humanized / Q000627:therapeutic use; D000970:Antineoplastic Agents / Q000627:therapeutic use; D018572:Disease-Free Survival; D005260:Female; D005434:Flow Cytometry; D000079982:Gemtuzumab; D006801:Humans; D016130:Immunophenotyping; D053208:Kaplan-Meier Estimate; D015470:Leukemia, Myeloid, Acute / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology; D008297:Male; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local / Q000453:epidemiology / Q000401:mortality; D018365:Neoplasm, Residual / Q000175:diagnosis*; D011379:Prognosis; D016016:Proportional Hazards Models; D012307:Risk Factors
D000617:Aminoglycosides; D061067:Antibodies, Monoclonal, Humanized; D000970:Antineoplastic Agents; D000079982:Gemtuzumab