Flow Cytometric Residual Disease Highly Prognostic in Older AML Patients
Older patients with acute myeloid leukemia (AML) have a high relapse rate after standard chemotherapy. In a study reported in Journal of Clinical Oncology, Sylvie D. Freeman, MD, PhD, of University Hospitals Birmingham National Health Service Trust, and colleagues investigated whether assessing chemotherapy sensitivity by multiparameter flow cytometric minimal residual disease detection has independent prognostic value in patients aged > 60 years. They found that early assessment of treatment response with multiparameter flow cytometry is highly prognostic in this setting.
Study Details
In the study, 892 unselected AML patients receiving intensive treatment in the United Kingdom National Cancer Research Institute AML16 Trial were assessed for multiparameter flow cytometric minimal residual disease during treatment. Of these, 833 had leukemia-associated immunophenotypes identified in pretreatment screening, and 427 entered complete remission after one or two courses of treatment and were assessable for multiparameter flow cytometric minimal residual disease by leukemia-associated immunophenotype detection in complete remission bone marrow for at least one of these time points. Minimal residual disease positivity was defined as residual disease detected by leukemia-associated immunophenotype.
Survival Analyses
Multiparameter flow cytometric minimal residual disease negativity was achieved in 51% of patients after course 1 and 64% after course 2. Compared with minimal residual disease–positive patients, minimal residual disease–negative patients had significantly greater 3-year overall survival from complete remission after course 1 (42% vs 26%, hazard ratio [HR] = 1.85, P < .001) and after course 2 (38% vs 18%, HR = 1.90, P < .001).
The prognostic significance of multiparameter flow cytometric minimal residual disease status after both course 1 and course 2 was retained in multivariable analyses adjusting for known prognostic factors, although the significance after course 2 was reduced. In multivariable analysis including minimal residual disease status after both course 1 and course 2, residual disease positivity after course 1 retained its significant prognostic value, whereas positivity after course 2 did not.
In analyses of the effect of multiparameter flow cytometric minimal residual disease status on overall survival after course 1 in specific genetic risk groups, there was no significant interaction with cytogenetic risk, with cytogenetics remaining the most significant prognostic indicator for survival, followed by minimal residual disease status and secondary disease. Minimal residual disease positivity after course 1 also retained its prognostic value after adjustment for NPM and FLT3 internal tandem duplication status.
Treatment with gemtuzumab ozogamicin (Mylotarg) in the AML16 trial improved survival primarily by reducing relapse while not increasing remission rate. More patients in the gemtuzumab ozogamicin group achieved minimal residual disease negativity than in the control arm (57% vs 48% of patients in complete remission after course 1), but the difference was not significant.
Relapse Analyses
Multiparameter flow cytometric minimal residual disease negativity was also associated with significantly reduced 3-year relapse rate after course 1 (71% vs 83%, HR = 2.05, P < .001) and course 2 (79% vs 91%, HR = 1.89, P < .001). There was a lower risk of early relapse in minimal residual disease–negative patients after course 1; median time to relapse was 8.5 vs 17.1 months, and 1- and 2-year rates were 40% vs 59% and 60% vs 79%, respectively.
The investigators concluded, “Early assessment of treatment response using flow cytometry provides powerful independent prognostic information in older adults with AML, lending support to the incorporation of [minimal residual disease] detection to refine risk stratification and inform clinical trial design in this challenging group of patients.”
The study was supported in part by Cancer Research UK.
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