Session: 617. Acute Myeloid Leukemias: Biomarkers, Molecular Markers and Minimal Residual Disease in Diagnosis and Prognosis: Poster I
Hematology Disease Topics & Pathways:
Research, Acute Myeloid Malignancies, AML, Translational Research, Diseases, Myeloid Malignancies, Minimal Residual Disease
The original LAIP approach encompasses determining the percentages of the LAIPs in the follow-up sample, which were also identified at diagnosis. For the LAIP-based-DfN approach, we followed the same approach, but determined the percentages of all possible LAIPs in the MFC-MRD panel at diagnosis and after C2. An emerging LAIP is defined as a LAIP that is present in the follow-up but was not found at diagnosis. MRD positivity was defined as ≥ 0.1% LAIP cells of white blood cells. Patients with an emerging LAIP < 0.1% or no LAIPs in follow-up would result in MRD negativity for LAIP-based-DfN, but was only possible when at least 500,000 cells were acquired in all four tubes.
At diagnosis, we received 884 samples of 905 patients (98%), in which we found a LAIP ≥ 10% of CD45dim blasts in 83% of the samples (Figure 1A). After C2, we received 615 samples, for which we had MFC-MRD results for 79% (487/615) by the LAIP approach. When we applied the LAIP-based-DfN approach, we scored 69 of 615 extra MRD results: an emerging LAIP ≥ 0.1% (MRDpos, N = 14), no LAIPs (MRDneg, N = 25) or an emerging LAIP < 0.1% (MRDneg, N = 30). When including these results in the data of the LAIP approach, the percentage of patients with an MRD result increased from 79% (487/615) to 90% (556/615), and the MRD positive percentage increased from 13% (81/615) to 19% (118/615)(Figure 1B). The LAIPs of emerging clones most often included CD56, CD15, and CD22. To assess the prognostic value in the HO132, we combined the reanalyzed LAIP-based-DfN MFC-MRD with the NPM1-MRD (N = 567). In these analyses, overall survival (OS) hazard ratio (HR) 95% confidence interval (CI) 1.92 (1.44-2.56) and relapse-free survival (RFS) HR 95% CI 1.7 (1.31-2.19) were similar to the original LAIP based/NPM1 approach: OS HR: 95%CI 2.02 (1.48-2.76) and RFS HR: 95%CI 1.78 (1.34-2.35), respectively.
In conclusion, the LAIP-based-DfN approach adds additional MRD results while retaining the prognostic value. Since HOVON-SAKK centers are highly compliant with the protocol and 98% of diagnosis samples were available, the LAIP-based-DfN approach can offer additional value for studies with limited access to diagnosis samples.
Disclosures: Gjertsen: BerGenBio: Consultancy; GreinDX: Consultancy; Immedica: Consultancy; InCyte: Consultancy; Mendus AB: Consultancy, Research Funding; Novartis: Consultancy, Research Funding; Otsuka: Consultancy; Pfizer: Consultancy, Research Funding; Sanofi: Consultancy; in Alden Cancer Therapy AS: Current holder of stock options in a privately-held company; KinN Therapeutics AS: Current holder of stock options in a privately-held company; Coegin: Consultancy. Griškevičius: Miltenyi Biomedicine: Membership on an entity's Board of Directors or advisory committees. Juliusson: AbbVie: Honoraria; Jazz: Honoraria; Laboratoire Delbert: Other: Research cooperation; Novartis: Honoraria; Servier: Honoraria. Löwenberg: F.Hoffmann La Roche: Membership on an entity's Board of Directors or advisory committees; 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. de Leeuw: Takeda: Membership on an entity's Board of Directors or advisory committees; Abbvie: Consultancy; Roche: Consultancy; Servier: Consultancy, Membership on an entity's Board of Directors or advisory committees; Ellipses Pharma: Research Funding. van de Loosdrecht: BMS: Membership on an entity's Board of Directors or advisory committees, Research Funding; Celgene: Membership on an entity's Board of Directors or advisory committees, Research Funding; Roche: Research Funding. Ossenkoppele: Servier: Consultancy; Abbvie: Consultancy; Roche: Consultancy, Membership on an entity's Board of Directors or advisory committees; Astellas: Consultancy, Honoraria; Gilead: Consultancy; Amgen: Consultancy; AGIOS: Consultancy, Honoraria; Janssen: Consultancy; BMS/Celgene: Consultancy, Honoraria; Pfizer: Research Funding; Novartis: Consultancy, Honoraria, Research Funding; JazzPharmaceuticals: Consultancy. Cloos: Navigate: Consultancy, Patents & Royalties: Royalties MRD assay; BD Biosciences: Patents & Royalties: Royalties LSC tube; Takeda: Research Funding; Astellas: Speakers Bureau; Novartis: Consultancy, Research Funding.