TY - JOUR
T1 - AML-513 The Role of FLT3 Inhibitors in Patients With Acute Myeloid Leukemia (AML) and T(6;9)(P22;Q34)
AU - Ong, Faustine
AU - Kadia, Tapan
AU - Short, Nicholas J.
AU - Yilmaz, Musa
AU - Alvarado, Yesid
AU - Sasaki, Koji
AU - Pierce, Sherry A.
AU - Garcia-Manero, Guillermo
AU - DiNardo, Courtney
AU - Borthakur, Gautam
AU - Konopleva, Marina
AU - Daver, Naval
AU - Kantarjian, Hagop
AU - Ravandi, Farhad
N1 - Publisher Copyright:
© 2022 Elsevier Inc.
PY - 2022/10
Y1 - 2022/10
N2 - Context: Efficacy of FLT3 inhibitors (FLT3-i) in patients with AML and t(6;9)(p22;q34)/DEK-NUP214 is not well-established. Objective: We compared overall survival (OS) and event-free survival (EFS) of AML patients with t(6;9) who received frontline FLT3-i, regardless of their FLT3 mutation status. Design: We evaluated patients with AML or high-risk myelodysplastic syndrome (HR-MDS) seen in our center between 1995-2021. Among 9936 patients, 55 patients (0.5%) had t(6;9) (48 AML, 7 HR-MDS). Patients were divided according to their induction regimen with (n:5) or without FLT3-i (n:48). Results: Among 47 patients, 35 were FLT3-ITD+, 5 had both ITD and TKD mutations. ITD allelic ratio (AR) was known for 28 (80%) patients (AR range: 0.01-0.95) with 11 (31%) patients having an AR ≥0.5. Age was well-balanced across both groups with median of 41 years. Ninety-two percent had ECOG performance status of 0-1 on presentation. Most patients in FLT3-i group (80%) and non-FLT3-i group (77%) received intensive chemotherapy. Sorafenib was used in 62% and quizartinib in 24% of cases. All patients in FLT3-i group and 71% in non-FLT3-i group were FLT3-ITD+. All patients in FLT3-i group achieved CR/CRi (60% MRD negative) as compared to 52% of non-FLT3-i group, and 60% of FLT3-i group had transplantation in CR1 (vs. 21% of non-FLT3-i). All groups received 1 cycle of therapy to reach CR/CRi. With median follow up of 47 months, 2-year OS and EFS were higher in FLT3-i than non-FLT3-i cohort (80% and 60% vs. 41% and 20%, respectively, p=0.2 for OS and 0.1 for EFS). Addition of FLT3-i improved 2-year EFS in FLT3-ITD+ patients (60% vs. 15% in non-FLT3-i regimen, p=0.07). Two-year OS and EFS were lower in FLT3-ITD+ patients than wild-type FLT3 patients (44% and 22% vs. 58% and 42%, respectively; p=0.4 for OS and 0.3 for EFS), regardless of FLT3-i therapy during induction. CR/CRi rate was similar between FLT3-ITD+ and wild-type FLT3 patients (57%) but more wild-type FLT3 patients received transplantation in CR1 (42%) than FLT3-ITD+ (23%). Conclusions: FLT3 mutation status does not impact survival in patients with t(6;9). Addition of FLT3-i in subset of patients with FLT3-ITD mutation is beneficial and should be further evaluated.
AB - Context: Efficacy of FLT3 inhibitors (FLT3-i) in patients with AML and t(6;9)(p22;q34)/DEK-NUP214 is not well-established. Objective: We compared overall survival (OS) and event-free survival (EFS) of AML patients with t(6;9) who received frontline FLT3-i, regardless of their FLT3 mutation status. Design: We evaluated patients with AML or high-risk myelodysplastic syndrome (HR-MDS) seen in our center between 1995-2021. Among 9936 patients, 55 patients (0.5%) had t(6;9) (48 AML, 7 HR-MDS). Patients were divided according to their induction regimen with (n:5) or without FLT3-i (n:48). Results: Among 47 patients, 35 were FLT3-ITD+, 5 had both ITD and TKD mutations. ITD allelic ratio (AR) was known for 28 (80%) patients (AR range: 0.01-0.95) with 11 (31%) patients having an AR ≥0.5. Age was well-balanced across both groups with median of 41 years. Ninety-two percent had ECOG performance status of 0-1 on presentation. Most patients in FLT3-i group (80%) and non-FLT3-i group (77%) received intensive chemotherapy. Sorafenib was used in 62% and quizartinib in 24% of cases. All patients in FLT3-i group and 71% in non-FLT3-i group were FLT3-ITD+. All patients in FLT3-i group achieved CR/CRi (60% MRD negative) as compared to 52% of non-FLT3-i group, and 60% of FLT3-i group had transplantation in CR1 (vs. 21% of non-FLT3-i). All groups received 1 cycle of therapy to reach CR/CRi. With median follow up of 47 months, 2-year OS and EFS were higher in FLT3-i than non-FLT3-i cohort (80% and 60% vs. 41% and 20%, respectively, p=0.2 for OS and 0.1 for EFS). Addition of FLT3-i improved 2-year EFS in FLT3-ITD+ patients (60% vs. 15% in non-FLT3-i regimen, p=0.07). Two-year OS and EFS were lower in FLT3-ITD+ patients than wild-type FLT3 patients (44% and 22% vs. 58% and 42%, respectively; p=0.4 for OS and 0.3 for EFS), regardless of FLT3-i therapy during induction. CR/CRi rate was similar between FLT3-ITD+ and wild-type FLT3 patients (57%) but more wild-type FLT3 patients received transplantation in CR1 (42%) than FLT3-ITD+ (23%). Conclusions: FLT3 mutation status does not impact survival in patients with t(6;9). Addition of FLT3-i in subset of patients with FLT3-ITD mutation is beneficial and should be further evaluated.
KW - acute myeloid leukemia
KW - AML
KW - chromosomal translocation
KW - FLT3 inhibitor
KW - FLT3-ITD
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U2 - 10.1016/S2152-2650(22)01309-X
DO - 10.1016/S2152-2650(22)01309-X
M3 - Article
C2 - 36163855
AN - SCOPUS:85138148387
SN - 2152-2650
VL - 22
SP - S258
JO - Clinical Lymphoma, Myeloma and Leukemia
JF - Clinical Lymphoma, Myeloma and Leukemia
ER -