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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.

Publikationen: SCORING: Beitrag in Fachzeitschrift/Zeitung › SCORING: Zeitschriftenaufsatz › Forschung › Begutachtung

Harvard

Rücker, FG, Bullinger, L, Cocciardi, S, Skambraks, S, Luck, TJ, Weber, D, Krzykalla, J, Pozek, E, Schneider, IJ, Corbacioglu, A, Gaidzik, VI, Meid, A, Aicher, S, Stegelmann, F, Schrade, A, Theis, F, Fiedler, W, Salih, HR, Wulf, GG, Salwender, HJ, Schroeder, T, Götze, KS, Kühn, MWM, Lübbert, M, Schlenk, RF, Benner, A, Thol, FR, Heuser, M, Ganser, A, Döhner, H & Döhner, K 2024, 'Measurable Residual Disease Monitoring in AML With FLT3-ITD Treated With Intensive Chemotherapy Plus Midostaurin', BLOOD ADV. https://doi.org/10.1182/bloodadvances.2024013758

APA

Rücker, F. G., Bullinger, L., Cocciardi, S., Skambraks, S., Luck, T. J., Weber, D., Krzykalla, J., Pozek, E., Schneider, I. J., Corbacioglu, A., Gaidzik, V. I., Meid, A., Aicher, S., Stegelmann, F., Schrade, A., Theis, F., Fiedler, W., Salih, H. R., Wulf, G. G., ... Döhner, K. (2024). Measurable Residual Disease Monitoring in AML With FLT3-ITD Treated With Intensive Chemotherapy Plus Midostaurin. BLOOD ADV. https://doi.org/10.1182/bloodadvances.2024013758

Vancouver

Rücker FG, Bullinger L, Cocciardi S, Skambraks S, Luck TJ, Weber D et al. Measurable Residual Disease Monitoring in AML With FLT3-ITD Treated With Intensive Chemotherapy Plus Midostaurin. BLOOD ADV. 2024 Sep 30. https://doi.org/10.1182/bloodadvances.2024013758

Bibtex

@article{a0707e477ee242888c305bee051243ce,
title = "Measurable Residual Disease Monitoring in AML With FLT3-ITD Treated With Intensive Chemotherapy Plus Midostaurin",
abstract = "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.",
author = "R{\"u}cker, {Frank G} and Lars Bullinger and Sibylle Cocciardi and Sabrina Skambraks and Luck, {Tamara J} and Daniela Weber and Julia Krzykalla and Ema Pozek and Schneider, {Isabelle Janina} and Andrea Corbacioglu and Gaidzik, {Verena I} and Annika Meid and Sophia Aicher and Frank Stegelmann and Anika Schrade and Frauke Theis and Walter Fiedler and Salih, {Helmut R} and Wulf, {Gerald G} and Salwender, {Hans J} and Thomas Schroeder and G{\"o}tze, {Katharina S} and K{\"u}hn, {Michael W M} and Michael L{\"u}bbert and Schlenk, {Richard F} and Axel Benner and Thol, {Felicitas R} and Michael Heuser and Arnold Ganser and Hartmut D{\"o}hner and Konstanze D{\"o}hner",
note = "Copyright {\textcopyright} 2024 American Society of Hematology.",
year = "2024",
month = sep,
day = "30",
doi = "10.1182/bloodadvances.2024013758",
language = "English",
journal = "BLOOD ADV",
issn = "2473-9529",
publisher = "Elsevier BV",

}

RIS

TY - JOUR

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 -