AML-440 Prognosis of Molecularly-Defined Secondary Acute Myeloid Leukemia Patients

TY - JOUR

T1 - AML-440 Prognosis of Molecularly-Defined Secondary Acute Myeloid Leukemia Patients

AU - Mecklenbrauck, Rabea

AU - Borchert, Nora

AU - Klement, Piroska

AU - Funke, Carolin

AU - Brandes, Maximilian

AU - Dallmann, Louisa-Kristin

AU - Fiedler, Walter

AU - Krauter, Jürgen

AU - Trummer, Arne

AU - Hertenstein, Bernd

AU - Voβ, Andreas

AU - Lübbert, Michael

AU - Gaidzik, Verena

AU - Döhner, Konstanze

AU - Döhner, Hartmut

AU - Ganser, Arnold

AU - Thol, Felicitas

AU - Heuser, Michael

N1 - Copyright © 2022 Elsevier Inc. All rights reserved.

PY - 2022/10/1

Y1 - 2022/10/1

N2 - INTRODUCTION: Mutations in ASXL1, BCOR, EZH2, SF3B1, SRSF2, STAG2, U2AF1 and ZRSR2 were proposed as secondary AML (sAML) defining mutations independent from the patients' history. We evaluated the prognostic impact of molecularly-defined sAML (msAML) patients in the context of the European LeukemiaNet (ELN) risk categories.METHODS: 459 adult newly-diagnosed AML patients (median age 54) with available genetic and follow-up data were included. Patients received standard induction and consolidation chemotherapy or underwent allogeneic hematopoietic cell transplantation (alloHCT). Patients were classified as de-novo AML (dnAML), msAML carrying ≥ 1 sAML-defining mutations, and clinically-defined secondary AML (csAML) based on previous medical history and cytogenetics.RESULTS: 208 (45%) patients had dnAML, 155 (34%) msAML, and 96 (21%) csAML. 62 msAML patients overlapped with csAML. Of msAML patients, 104 (67%) had 1, 39 (25%) 2, and 12 (8%) 3 or more msAML-defining mutations. The most frequently mutated msAML-defining genes were ASXL1 (n=48, 31%) and SRSF2 (n=44, 28%). The likelihood to reach complete remission (CR) was higher for dnAML compared to msAML patients (92% vs 79%, P =.003), but there was no difference between csAML and msAML patients. The median follow-up of all patients was 5.56 years. The transplantation rate in first CR was similar in dnAML, msAML and csAML patients (33%, 37%, 44%, respectively). Overall survival (OS) was significantly worse in msAML compared to dnAML patients (median OS 3.3 years vs not reached, HR = 1.7, 95%CI 1.2-2.2, P<.001), also when ASXL1 mutated patients were excluded (HR = 1.7, 95%CI 1.2-2.4, P<.001). OS was similar in csAML vs dnAML and in msAML vs csAML patients. In the ELN favorable and intermediate risk groups msAML patients (n=19 and n=52) had a significantly worse OS compared to dnAML patients (n=66 and n=80) (HR=3.1 95%CI 1.5-6.3, P=.001 and HR=2, 95%CI 1.2-3.2, P=.008, respectively). OS was similar in the ELN adverse risk group between msAML (n=79) and dnAML patients (n=31). Accordingly, the ELN risk groups did not stratify OS in msAML patients.CONCLUSIONS: msAML-defining mutations identify a subgroup of dnAML patients with poor prognosis and reclassify 10% of all patients in our cohort from favorable/intermediate to the adverse risk group.

AB - INTRODUCTION: Mutations in ASXL1, BCOR, EZH2, SF3B1, SRSF2, STAG2, U2AF1 and ZRSR2 were proposed as secondary AML (sAML) defining mutations independent from the patients' history. We evaluated the prognostic impact of molecularly-defined sAML (msAML) patients in the context of the European LeukemiaNet (ELN) risk categories.METHODS: 459 adult newly-diagnosed AML patients (median age 54) with available genetic and follow-up data were included. Patients received standard induction and consolidation chemotherapy or underwent allogeneic hematopoietic cell transplantation (alloHCT). Patients were classified as de-novo AML (dnAML), msAML carrying ≥ 1 sAML-defining mutations, and clinically-defined secondary AML (csAML) based on previous medical history and cytogenetics.RESULTS: 208 (45%) patients had dnAML, 155 (34%) msAML, and 96 (21%) csAML. 62 msAML patients overlapped with csAML. Of msAML patients, 104 (67%) had 1, 39 (25%) 2, and 12 (8%) 3 or more msAML-defining mutations. The most frequently mutated msAML-defining genes were ASXL1 (n=48, 31%) and SRSF2 (n=44, 28%). The likelihood to reach complete remission (CR) was higher for dnAML compared to msAML patients (92% vs 79%, P =.003), but there was no difference between csAML and msAML patients. The median follow-up of all patients was 5.56 years. The transplantation rate in first CR was similar in dnAML, msAML and csAML patients (33%, 37%, 44%, respectively). Overall survival (OS) was significantly worse in msAML compared to dnAML patients (median OS 3.3 years vs not reached, HR = 1.7, 95%CI 1.2-2.2, P<.001), also when ASXL1 mutated patients were excluded (HR = 1.7, 95%CI 1.2-2.4, P<.001). OS was similar in csAML vs dnAML and in msAML vs csAML patients. In the ELN favorable and intermediate risk groups msAML patients (n=19 and n=52) had a significantly worse OS compared to dnAML patients (n=66 and n=80) (HR=3.1 95%CI 1.5-6.3, P=.001 and HR=2, 95%CI 1.2-3.2, P=.008, respectively). OS was similar in the ELN adverse risk group between msAML (n=79) and dnAML patients (n=31). Accordingly, the ELN risk groups did not stratify OS in msAML patients.CONCLUSIONS: msAML-defining mutations identify a subgroup of dnAML patients with poor prognosis and reclassify 10% of all patients in our cohort from favorable/intermediate to the adverse risk group.

KW - Adult

KW - Humans

KW - Leukemia, Myeloid, Acute/diagnosis

KW - Middle Aged

KW - Mutation

KW - Neoplasms, Second Primary

KW - Prognosis

KW - Remission Induction

KW - Splicing Factor U2AF/genetics

U2 - 10.1016/S2152-2650(22)01297-6

DO - 10.1016/S2152-2650(22)01297-6

M3 - Other (editorial matter etc.)

C2 - 36163842

VL - 22

SP - S251-S252

JO - CL LYMPH MYELOM LEUK

JF - CL LYMPH MYELOM LEUK

SN - 2152-2650

IS - Suppl 2

ER -