Postinduction MRD Predicts Outcome From Transplantation in NPM1-Mutant AML

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In an analysis of a French trial reported in the Journal of Clinical Oncology, Balsat et al found that postinduction minimal residual disease was predictive of outcome and benefit from allogeneic stem cell transplantation (ASCT) in patients with NPM1-mutant acute myeloid leukemia (AML). Nicolas Boissel, MD, PhD, of Saint-Louis University Hospital, Paris, is the corresponding author of the Journal of Clinical Oncology article.

The study involved 229 patients aged 18 to 60 years with NPM1-mutant disease in the Acute Leukemia French Association 0702 (ALFA-0702) trial. Among them, minimal residual disease evaluation was available for 152 patients in first remission. Patients with nonfavorable AML, according to the European LeukemiaNet classification, were eligible for ASCT in first remission.

Minimal Residual Disease and Outcome

Failure to achieve a 4-log reduction in NPM1-mutant peripheral blood–minimal residual disease after induction therapy was associated with a higher cumulative incidence of relapse (subhazard ratio [SHR] = 5.83, P < .001) and poorer overall survival (hazard ratio [HR] = 10.99, P < .001). For example, 3-year overall survival was 40.8% in those with < 4 log reduction, 91.2% with a 4- to 5-log reduction, and 93.1% with > 5 log reduction.

In multivariable analysis, abnormal karyotype, presence of FLT3–internal tandem duplication, and a < 4-log reduction in peripheral blood–minimal residual disease were significantly associated with a higher relapse incidence and shorter overall survival (HR for overall survival = 5.10, P < .001, for < 4-log reduction in peripheral blood–minimal residual disease).

Among patients with FLT3–internal tandem duplication, only age, white blood cell count, and < 4-log reduction in peripheral blood–minimal residual disease (SHR = 3.29, P = .02) were significantly associated with a higher cumulative incidence of relapse.

Effect of ASCT

In patients with nonfavorable AML, disease-free survival (HR = 0.25, P = .047) and overall survival (HR = 0.25, P = .047) were significantly improved by ASCT in those with a < 4-log reduction in peripheral blood–minimal residual disease. No such benefit was observed in those patients with a > 4-log reduction, with the interaction between peripheral blood–minimal residual disease response and ASCT effect being significant for both disease-free (P = .024) and overall survival (P = .027).

The investigators concluded: “Our study supports the strong prognostic significance of early NPM1 [mutant] [peripheral blood–minimal residual disease], independent of the cytogenetic and molecular context. Moreover, NPM1 [mutant] [peripheral blood–minimal residual disease] may be used as a predictive factor for ASCT indication.” ■

Balsat M, et al: J Clin Oncol 35:185-193, 2017.




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