Measurable residual disease by flow cytometry in acute myeloid leukemia is prognostic, independent of genomic profiling.

Measurable residual disease (MRD) assessment provides a potent indicator of the efficacy of anti-leukemic therapy. It is unknown, however, whether integrating MRD with molecular profiling better identifies patients at risk of relapse. To investigate the clinical relevance of MRD in relation to a molecular-based prognostic schema, we measured MRD by flow cytometry in 189 AML patients enrolled in ECOG-ACRIN E1900 trial (NCT00049517) in morphologic complete remission (CR) (28.8 % of the original cohort) representing 44.4 % of CR patients. MRD positivity was defined as ≥ 0.1 % of leukemic bone marrow cells. Risk classification was based on standard cytogenetics, fluorescence-in-situ-hybridization, somatic gene analysis, and sparse whole genome sequencing for copy number ascertainment. At 84.6 months median follow-up of patients still alive at the time of analysis (range 47.0-120 months), multivariate analysis demonstrated that MRD status at CR (p = 0.001) and integrated molecular risk (p = 0.0004) independently predicted overall survival (OS). Among risk classes, MRD status significantly affected OS only in the favorable risk group (p = 0.002). Expression of CD25 (α-chain of the interleukin-2 receptor) by leukemic myeloblasts at diagnosis negatively affected OS independent of post-treatment MRD levels. These data suggest that integrating MRD with genetic profiling and pre-treatment CD25 expression may improve prognostication in AML.

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Conflict-of-interest disclosure E.P. does consulting work with Supertechs Inc. and the ECOG-ACRIN Cancer Research Group; R.L.L. is on the supervisory board of Qiagen and is a scientific advisor for Imago, Mission Bio, Zentalis, Ajax, Auron, Prelude, C4 Therapeutics and Isoplexis; he receives research support from and consulted for Celgene and Roche and has consulted for Incyte, Janssen, Astellas, Morphosys and Novartis; he has received honoraria from Roche, Lilly and Amgen for invited lectures and from Gilead for grant reviews. O.I.A.-W. has served as a consultant for H3B Biomedicine, Foundation Medicine Inc, Merck, Prelude Therapeutics and Janssen and is on the scientific advisory board of Envisagenics Inc, Pfizer Boulder and AlChemy Inc; he has received prior research funding from Loxo Oncology and H3B Biomedicine. M.S.T. receives research funding from Abbvie, Cellerant, Orsenix, ADC Therapeutics, Biosight, Glycomimetics, Rafael Pharmaceuticals and Amgen, is on the advisory boards of Abbvie, BioLineRx, Daiichi-Sankyo, Orsenix, KAHR, Rigel, Nohla, Delta Fly Pharma, Tetraphase, Oncolyze, Jazz Pharmaceuticals, Roche, Biosight, Novartis, and receives royalties from UpToDate. H.F.F. serves on the advisory board of Jazz Pharmaceuticals and Incyte. S.W.L. is founder and member of the scientific advisory board of Blueprint Medicines, Mirimus, ORIC Pharmaceuticals and Faeth Therapeutics, and is on the scientific advisory board of Constellation Pharmaceuticals and PMV Pharmaceuticals. H.M.L. is a promotional speaker and consultant for Jazz Pharmaceuticals. The remaining authors declare no competing financial interests.