TY - JOUR
T1 - Midostaurin in combination with chemotherapy is most effective in patients with acute myeloid leukemia presenting with high FLT3-ITD allelic ratio who proceed to allogeneic stem cell transplantation while in first complete remission
AU - Ofran, Yishai
AU - Leiba, Ronit
AU - Frisch, Avraham
AU - Horesh, Nurit
AU - Henig, Israel
AU - Yehudai-Ofir, Dana
AU - Moshe, Yakir
AU - Neaman, Miriam
AU - Ganzel, Chezi
AU - Gal-Rabinovich, Kinneret
AU - Hellmann, Ilana
AU - Weinstein, Vladimir
AU - Berger, Tamar
AU - Wolach, Ofir
N1 - Publisher Copyright:
© 2020 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd
PY - 2021/1
Y1 - 2021/1
N2 - Objectives: Midostaurin, a multikinase and FLT3 inhibitor, is the first non-chemotherapy agent approved and widely adopted for the treatment of FLT3-ITD acute myeloid leukemia (AML). Yet, its role in improving survival of patients referred to allogeneic stem cell transplantation (allo-SCT) in first complete remission (CR1) needs to be defined. Methods: This multicenter study retrospectively evaluated the outcome of 119 FLT3-ITD AML patients [59 (49.6%) males and 60 females] intensively treated between 2015 and 2019 at five Israeli centers. In our cohort, allo-SCT in CR1 was widely implemented (47%) and patient stratification was based on the current allelic ratio (AR) cutoff of 0.5. Results: Ninety-eight patients (82.3%) achieved CR1/CR with incomplete count recovery (CRi). Death during induction was reported in 7 (5.9%) patients. In multivariate analysis, midostaurin use and allo-SCT in CR1 were the most significant factors affecting overall survival (OS). Midostaurin incorporation in chemotherapy regimens significantly improved CR + CRi rates (P =.002), reduced relapse rates (P =.02), and was remarkably advantageous for high-AR patients (2-year OS 82%). In low-AR patients, the midostaurin effect was much less prominent. Conclusions: Our results demonstrate benefits of midostaurin incorporation in intensive chemotherapy regimens, particularly for high-AR AML patients to whom it should be offered along with allo-SCT in CR1.
AB - Objectives: Midostaurin, a multikinase and FLT3 inhibitor, is the first non-chemotherapy agent approved and widely adopted for the treatment of FLT3-ITD acute myeloid leukemia (AML). Yet, its role in improving survival of patients referred to allogeneic stem cell transplantation (allo-SCT) in first complete remission (CR1) needs to be defined. Methods: This multicenter study retrospectively evaluated the outcome of 119 FLT3-ITD AML patients [59 (49.6%) males and 60 females] intensively treated between 2015 and 2019 at five Israeli centers. In our cohort, allo-SCT in CR1 was widely implemented (47%) and patient stratification was based on the current allelic ratio (AR) cutoff of 0.5. Results: Ninety-eight patients (82.3%) achieved CR1/CR with incomplete count recovery (CRi). Death during induction was reported in 7 (5.9%) patients. In multivariate analysis, midostaurin use and allo-SCT in CR1 were the most significant factors affecting overall survival (OS). Midostaurin incorporation in chemotherapy regimens significantly improved CR + CRi rates (P =.002), reduced relapse rates (P =.02), and was remarkably advantageous for high-AR patients (2-year OS 82%). In low-AR patients, the midostaurin effect was much less prominent. Conclusions: Our results demonstrate benefits of midostaurin incorporation in intensive chemotherapy regimens, particularly for high-AR AML patients to whom it should be offered along with allo-SCT in CR1.
KW - acute myeloid leukemia
KW - allogeneic stem cell transplantation
KW - fms-like tyrosine kinase 3-internal tandem duplication
KW - midostaurin
UR - http://www.scopus.com/inward/record.url?scp=85092089515&partnerID=8YFLogxK
U2 - 10.1111/ejh.13518
DO - 10.1111/ejh.13518
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C2 - 32949053
AN - SCOPUS:85092089515
SN - 0902-4441
VL - 106
SP - 64
EP - 71
JO - European Journal of Haematology
JF - European Journal of Haematology
IS - 1
ER -