Azacitidine for Pre-Emptive Treatment of Measurable-Residual Disease in MDS/AML Patients at High Risk of Hematological Relapse: Results of the Second Cohort of the RELAZA2 Trial

▪ Background: Measurable residual disease (MRD) can identify patients (pts) with myelodysplastic syndrome (MDS) or acute myeloid leukemia (AML) in complete hematological remission (CR) at high risk of relapse even after allogeneic hematopoietic stem cell transplantation (HSCT). We have recently show...

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Published in:Blood 2019-11, Vol.134 (Supplement_1), p.644-644
Main Authors: Platzbecker, Uwe, Middeke, Jan Moritz, Sockel, Katja, Herbst, Regina, Fransecky, Lars R., Wolf, Dominik, Martin, Schumacher, Krämer, Alwin, Noppeney, Richard, Novotny, Juergen, Bug, Gesine, Götze, Katharina, Spiekermann, Karsten, Stelljes, Matthias, Groth, Christoph, Subklewe, Marion, Schubert, Antje, Mütherig, Anke, Bochtler, Tilmann, Mende, Marika, Kubasch, Anne Sophie, Hänel, Mathias, Dührsen, Ulrich, Schetelig, Johannes, Röllig, Christoph, Baldus, Claudia D, Ehninger, Gerhard, Müller-Tidow, Carsten, Serve, Hubert, Kramer, Michael, Bornhäuser, Martin, Thiede, Christian
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Language:English
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Summary:▪ Background: Measurable residual disease (MRD) can identify patients (pts) with myelodysplastic syndrome (MDS) or acute myeloid leukemia (AML) in complete hematological remission (CR) at high risk of relapse even after allogeneic hematopoietic stem cell transplantation (HSCT). We have recently shown in 53 pts treated within the first cohort of the RELAZA2 trial that pre-emptive therapy with azacitidine (AZA) at the time of MRD-positivity (MRDpos) can successfully prevent imminent hematological relapse (Platzbecker et al. Lancet Oncol. 2018). We now report on the results of the second cohort of 41 pts undergoing MRD-guided treatment in the RELAZA2 trial (ClinicalTrials.gov NCT01462578) by the Study Alliance Leukemia (SAL). Methods: Between 2015 and 2018, 166 MDS/AML pts were screened and centrally monitored for MRD in bone marrow or peripheral blood at monthly intervals for a period of 2 years prospectively in 9 centers in Germany. Of these 166, 41 pts with either advanced MDS (n=6) or AML (n=35) in CR after either conventional chemotherapy only (n=13) or consecutive allogeneic HSCT (n=28) developed MRD above a threshold defining imminent hematological relapse. Still being in morphological CR, these pts pre-emptively received 6 cycles of AZA (75mg/m2, s.c. days 1-7), which was followed by a risk-adapted AZA-maintenance therapy based on MRD-response for up to 18 additional months. Pts developing a hematological relapse went off study. MRD was detected by either the quantification of NPM1 mutation level (n=19), leukemia-specific fusion genes DEK-NUP214 (n=1) or RUNX1/RUNX1T1 (n=2) or a sensitive donor chimerism analysis of sorted CD34(+)/CD117(+) peripheral blood cells (n=28) in pts undergoing allogeneic HSCT. Here, we report the analysis of the primary endpoint of the 41 pts in the second cohort as well as the data for the entire 94 pts who entered the treatment phase of the RELAZA-2 study. Results: At a median of 110 days (range 28-476) after start of screening, 41 (25%) out of 166 prospectively screened pts became MRDpos as defined by either a decrease of CD34(+)/CD117(+) donor chimerism to 1% (NPM1 n=18) while being still in hematological CR. All of these MRDpos pts started AZA-based pre-emptive treatment to prevent imminent hematological relapse. Six months after start of MRD-guided therapy, 25 out of 41 pts were still in CR (61%, 95%-CI 45-76%, p
ISSN:0006-4971
1528-0020
DOI:10.1182/blood-2019-129926