Measurable Residual Disease Monitoring in AML With FLT3-ITD Treated With Intensive Chemotherapy Plus Midostaurin
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Measurable Residual Disease Monitoring in AML With FLT3-ITD Treated With Intensive Chemotherapy Plus Midostaurin. / Rücker, Frank G; Bullinger, Lars; Cocciardi, Sibylle; Skambraks, Sabrina; Luck, Tamara J; Weber, Daniela; Krzykalla, Julia; Pozek, Ema; Schneider, Isabelle Janina; Corbacioglu, Andrea; Gaidzik, Verena I; Meid, Annika; Aicher, Sophia; Stegelmann, Frank; Schrade, Anika; Theis, Frauke; Fiedler, Walter; Salih, Helmut R; Wulf, Gerald G; Salwender, Hans J; Schroeder, Thomas; Götze, Katharina S; Kühn, Michael W M; Lübbert, Michael; Schlenk, Richard F; Benner, Axel; Thol, Felicitas R; Heuser, Michael; Ganser, Arnold; Döhner, Hartmut; Döhner, Konstanze.
In: BLOOD ADV, 30.09.2024.Research output: SCORING: Contribution to journal › SCORING: Journal article › Research › peer-review
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T1 - Measurable Residual Disease Monitoring in AML With FLT3-ITD Treated With Intensive Chemotherapy Plus Midostaurin
AU - Rücker, Frank G
AU - Bullinger, Lars
AU - Cocciardi, Sibylle
AU - Skambraks, Sabrina
AU - Luck, Tamara J
AU - Weber, Daniela
AU - Krzykalla, Julia
AU - Pozek, Ema
AU - Schneider, Isabelle Janina
AU - Corbacioglu, Andrea
AU - Gaidzik, Verena I
AU - Meid, Annika
AU - Aicher, Sophia
AU - Stegelmann, Frank
AU - Schrade, Anika
AU - Theis, Frauke
AU - Fiedler, Walter
AU - Salih, Helmut R
AU - Wulf, Gerald G
AU - Salwender, Hans J
AU - Schroeder, Thomas
AU - Götze, Katharina S
AU - Kühn, Michael W M
AU - Lübbert, Michael
AU - Schlenk, Richard F
AU - Benner, Axel
AU - Thol, Felicitas R
AU - Heuser, Michael
AU - Ganser, Arnold
AU - Döhner, Hartmut
AU - Döhner, Konstanze
N1 - Copyright © 2024 American Society of Hematology.
PY - 2024/9/30
Y1 - 2024/9/30
N2 - Measurable residual disease (MRD) monitoring in acute myeloid leukemia (AML) with FLT3 internal tandem duplication (FLT3-ITDpos) was hampered by the broad heterogeneity of ITD mutations. Using our recently developed FLT3-ITD paired-end next-generation sequencing (NGS)-based MRD assay with a limit of detection of 10-4 to 10-5, we evaluated the prognostic impact of MRD at different time-points in 157 FLT3-ITDpos AML patients enrolled in the AMLSG16-10 trial (NCT01477606) combining intensive chemotherapy with midostaurin followed by midostaurin maintenance. Achievement of MRD negativity (MRDneg) after two cycles of chemotherapy (Cy2) observed in 111/142 (78%) patients predicted for superior 4-year rates of cumulative incidence of relapse (CIR) (4y-CIR, 26% vs 46%; P=.001) and overall survival (OS) (4y-OS, 70% vs 44%; P=.012). This survival advantage was also seen for patients undergoing allogeneic hematopoietic-cell transplantation in first complete remission (4y-CIR, 14% vs 39%; P=.001; 4y-OS, 71% vs 49%; P=.029). Multivariate models for CIR and OS after Cy2 revealed FLT3-ITD MRDneg as the only consistent favorable variable for CIR (HR, 0.29; P=.006) and OS (HR, 0.39; P=.018). NPM1 co-mutation correlated with deeper molecular response as reflected by stronger MRD reduction and higher rate of FLT3-ITD MRDneg after Cy2. During follow-up, conversion from MRDneg to MRDpos was a strong, independent factor for inferior CIR (HR, 16.64; P<.001) and OS (HR, 4.05; P<.001). NGS-based FLT3-ITD MRD monitoring allows for the identification of patients at high risk of relapse and death following intensive chemotherapy plus midostaurin. Using NGS-based technology, FLT3-ITD emerges as a novel, clinically highly relevant target for MRD monitoring.
AB - Measurable residual disease (MRD) monitoring in acute myeloid leukemia (AML) with FLT3 internal tandem duplication (FLT3-ITDpos) was hampered by the broad heterogeneity of ITD mutations. Using our recently developed FLT3-ITD paired-end next-generation sequencing (NGS)-based MRD assay with a limit of detection of 10-4 to 10-5, we evaluated the prognostic impact of MRD at different time-points in 157 FLT3-ITDpos AML patients enrolled in the AMLSG16-10 trial (NCT01477606) combining intensive chemotherapy with midostaurin followed by midostaurin maintenance. Achievement of MRD negativity (MRDneg) after two cycles of chemotherapy (Cy2) observed in 111/142 (78%) patients predicted for superior 4-year rates of cumulative incidence of relapse (CIR) (4y-CIR, 26% vs 46%; P=.001) and overall survival (OS) (4y-OS, 70% vs 44%; P=.012). This survival advantage was also seen for patients undergoing allogeneic hematopoietic-cell transplantation in first complete remission (4y-CIR, 14% vs 39%; P=.001; 4y-OS, 71% vs 49%; P=.029). Multivariate models for CIR and OS after Cy2 revealed FLT3-ITD MRDneg as the only consistent favorable variable for CIR (HR, 0.29; P=.006) and OS (HR, 0.39; P=.018). NPM1 co-mutation correlated with deeper molecular response as reflected by stronger MRD reduction and higher rate of FLT3-ITD MRDneg after Cy2. During follow-up, conversion from MRDneg to MRDpos was a strong, independent factor for inferior CIR (HR, 16.64; P<.001) and OS (HR, 4.05; P<.001). NGS-based FLT3-ITD MRD monitoring allows for the identification of patients at high risk of relapse and death following intensive chemotherapy plus midostaurin. Using NGS-based technology, FLT3-ITD emerges as a novel, clinically highly relevant target for MRD monitoring.
U2 - 10.1182/bloodadvances.2024013758
DO - 10.1182/bloodadvances.2024013758
M3 - SCORING: Journal article
C2 - 39348668
JO - BLOOD ADV
JF - BLOOD ADV
SN - 2473-9529
ER -