Session: 617. Acute Myeloid Leukemias: Biomarkers, Molecular Markers and Minimal Residual Disease in Diagnosis and Prognosis: Poster III
Hematology Disease Topics & Pathways:
Research, adult, Translational Research, assays, Technology and Procedures, Study Population, Human, Minimal Residual Disease
In the current study, we prospectively validated the prognostic value of LSC burden at the following time points, i.e. at diagnosis (764/905 patients) and after two cycles of chemotherapy (C2; 357/706 patients). The median WBC acquired was 2x106 (range: 3x104- 6x106) at diagnosis and 3x106 (range: 4x105-5x106) after C2. Median percentages of LSC at diagnosis and after C2 were respectively 0.004% (range: 0.0000%-26.85%) and 0.00002% (range: 0.0000%-1.36%). Similar to the HOVON-SAKK102 study, three prognostic groups based on the presence or absence of CD34 and/or LSC, showed significant associations between LSC burden at diagnosis and overall survival (OS) or relapse- free survival (RFS) (Figure 1A): 1. CD34negative patients without any measurable LSCs and Leukemia Associated Immunophenotypes on the CD34+ blasts fraction (CD34negLSC=0 3 years (yrs) OS: 76.4% standard error (SE) 5; median OS not reached). 2. Patients with low percentages of CD34+CD38-LSCs < 0.03% (LSClow; 3 yrs OS 62.8% SE 2; median OS not reached) 3. Patients with high percentages of CD34+CD38-LSCs ≥0.03% (LSChigh, 3 yrs OS 44.5% SE 3; median 25.6 months; 95% confidence interval (CI): 18.7-49.1). Multivariate analysis adjusted for age, WBC at diagnosis, AML type, ELN2017 risk group and -only for RFS- the number of chemotherapy cycles to attain complete remission, showed that LSC burden at diagnosis is a strong independent prognostic factor for OS and RFS (Figure 1B). After C2, before the consolidation treatment, a cut-off value of 0.000075% of LSC showed the best prognostic value of LSC (univariate, LSCneg versus LSCpos: OS, HR 1.79 95% CI: 1.25-2.56, P < 0.01; RFS, HR 1.55, 95% CI: 1.12-2.13, P < 0.01). This cut-off appeared also highly significant as a prognostic factor in former trials (Terwijn et al. PLoS One 2014; Zeijlemaker et al. Leukemia 2018). Multivariate analysis showed that also LSC status after C2 was an independent prognostic factor for OS and RFS (Figure 1B). By combining the LSC status after C2 (≥0.000075%) together with the MRD status as used in the HOVON-SAKK 132 (based on ≥0.1% MFC-MRD and/or NPM1-MRD), MRDpos patients who are LSCpos have worse prognosis in OS and RFS (univariate: MRDnegLSCneg vs MRDposLSCpos; OS HR 3.2, 95% CI: 1.94-5.28, P < 0.01, RFS: HR 2.61 95% CI: 1.65-4.12, P < 0.01, multivariate: Figure 1B). Further analyses of the data are now directed towards potential influences of the cell amount of acquisition, ELN risk groups and MRD guidance in this trial. In conclusion, this prospective validation confirmed that assessing LSC burden, at diagnosis and after C2, remains to have additional prognostic value to MRD.
Disclosures: Gjertsen: Novartis: Consultancy; KinN Therapeutics: Current holder of stock options in a privately-held company; Alden Cancer Therapy: Current holder of stock options in a privately-held company; Pfizer Inc: Consultancy; BerGenBio: Consultancy. Griškevičius: Miltenyi Biomedicine: Membership on an entity's Board of Directors or advisory committees. Manz: University of Zurich: Patents & Royalties: CD117xCD3 TEA; CDR-Life Inc: Consultancy, Current holder of stock options in a privately-held company. Porkka: Pfizer: Honoraria; Celgene/Bristol-Myers Squibb: Research Funding; Incyte: Research Funding; Pfizer: Research Funding; Novartis: Research Funding; Novartis: Honoraria; Incyte: Honoraria; Bristol-Myers Squibb: Honoraria; Astellas: Honoraria; AbbVie: Honoraria. Lowenberg: Clear Creek Bio: Consultancy, Honoraria; Celgene: Membership on an entity's Board of Directors or advisory committees; Bristol Myers Squibb: Membership on an entity's Board of Directors or advisory committees; Catamaran Bio Inc: Membership on an entity's Board of Directors or advisory committees; Astellas: Membership on an entity's Board of Directors or advisory committees; AbbVie: Membership on an entity's Board of Directors or advisory committees; F. Hoffmann La Roche: Membership on an entity's Board of Directors or advisory committees. de Leeuw: Roche: Honoraria; Servier: Honoraria, Membership on an entity's Board of Directors or advisory committees; AbbVie: Consultancy, Honoraria; Takeda: Membership on an entity's Board of Directors or advisory committees. Janssen: Incyte Biosciences Benelux BV: Research Funding, Speakers Bureau; Pfizer: Consultancy; Uppsala County Council: Research Funding; Glycomimetics: Research Funding; Avillion: Research Funding; Ellipses Pharma: Research Funding; Roche: Speakers Bureau; Celgene: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Novartis: Consultancy, Research Funding; Bristol-Myers Squibb: Consultancy, Research Funding. Ossenkoppele: Jazz Pharmaceuticals: Consultancy; Roche: Consultancy, Membership on an entity's Board of Directors or advisory committees; Astellas: Consultancy, Honoraria; Gilead: Consultancy, Honoraria; Amgen: Consultancy; AGIOS: Consultancy, Honoraria; Janssen: Consultancy; BMS/Celgene: Consultancy, Honoraria; Pfizer: Consultancy; Novartis: Consultancy, Honoraria, Research Funding; Merus: Consultancy. Cloos: Navigate: Patents & Royalties: Royalties for MRD analyses; DC-One: Other: MRD assessments, Research Funding; Genentech: Research Funding; Janssen: Research Funding; Novartis: Consultancy, Other: MRD assessments, Research Funding; Astellas: Speakers Bureau; Merus: Other: MRD assessments, Research Funding; Helsinn: Other: MRD assessments; Takeda: Research Funding.