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796 Allogeneic Hematopoietic Cell Transplantation Can Overcome the Adverse Prognosis of Secondary-Type Mutation Positive De Novo Acute Myeloid Leukemia

Program: Oral and Poster Abstracts
Type: Oral
Session: 613. Acute Myeloid Leukemia: Clinical and Epidemiological: Practice-changing studies
Hematology Disease Topics & Pathways:
Clinical Research, Health Outcomes Research
Monday, December 13, 2021: 5:15 PM

Ga-Young Song1*, Taehyung Kim, MSc2,3, Seo-Yeon Ahn, MD1*, Sung-Hoon Jung, MD1*, Mihee Kim, MD1,4*, Deok-Hwan Yang, MD, PhD1*, Je-Jung Lee, MD, PhD1, Seunghyun Choi, PhD5*, MiYeon Kim5*, Chul Won Jung, MD, PhD6*, Jun-Ho Jang, MD6*, Hee-Je Kim, M.D., Ph.D.7, Joon Ho Moon, MD8, Sang Kyun Sohn, MD, PhD8*, Jong Ho Won9, Seong Kyu Park, MD9*, Sung-Hyun Kim, MD, PhD10, Zhaolei Zhang, PhD2,11,12*, Jae-Sook Ahn, MD, PhD1,5*, Hyeoung-Joon Kim, MD, PhD1,5 and Dennis Dong Hwan Kim Sr., MD13

1Department of Hematology-Oncology, Chonnam National University Hwasun Hospital, Jeollanam-do, Korea, Republic of (South)
2Department of Computer Science, University of Toronto, Toronto, ON, Canada
3The Donnelly Centre for Cellular and Biomolecular Research, Donnelly Centre For Cellular & Biomolecular Research, Toronto, ON, Canada
4Department of Hematology-Oncology, Chonnam National University Hwasun Hospital, Chonnam National University, Hwasun-Gun, Jeollanam-Do,, AL, Korea, Republic of (South)
5Genomic Research Center for Hematopoietic Diseases, Chonnam National University Hwasun Hospital, Jeollanam-do, Korea, Republic of (South)
6Division of Hematology-Oncology, Samsung Medical Center, Seoul, Korea, Republic of (South)
7Department of Hematology, Catholic Hematology Hospital, Seoul St. Mary's Hospital, College of Medicine, The Catholic University of Korea, Seoul, Korea, Republic of (South)
8Department of Hematology-Oncology, Kyungpook National University Hospital, Daegu, Korea, Republic of (South)
9Department of Hematology-Oncology, Soonchunhyang University Hospital, Seoul, Korea, Republic of (South)
10Department of Hematology-Oncology, Dong-A University College of Medicine, Dong-A University Hospital, Busan, Korea, Republic of (South)
11Department of Molecular Genetics, University of Toronto, Toronto, ON, Canada
12The Donnelly Centre for Cellular and Biomolecular Research, University of Toronto, Toronto, ON, Canada
13Department of Medical Oncology and Hematology, Princess Margaret Hospital, Toronto, ON, Canada

Secondary-type mutation (STM) in 8 genes including SRSF2, SF3B1, U2AF1, ZRSR2, ASXL1, EZH2, BCOR, and STAG2, is more frequently detected in secondary acute myeloid leukemia (AML) compared to de novo AML. However, it is still not clear whether de novo AML with STM is to be managed differently. Also, the role of allogeneic hematopoietic cell transplantation (HCT) is not fully defined in de novo AML patients with STM. Therefore, we evaluated the clinical significance of STM in de novo AML analyzing 393 patients diagnosed with de novo AML who had normal karyotype and received intensive induction therapy. Through the genetic profiling including the targeted deep sequencing of 35 genes, 60 patients (15.3%) carried secondary-type mutations (STM+) and 333 patients did not (STM-). The complete response (CR) rate was lower in the STM+ group (68.3% vs. 87.4%, p<0.001). The STM+ group showed significantly shorter overall survival (OS) than the STM- group (5-year 15.0% vs. 31.2%) (HR;1.983, 95% CI;1.454-2.704, p<0.001). Among the 332 patients who achieved CR, RFS was also worse in the STM+ group (5-year RFS 19.5% vs. 31.3%) (HR; 1.574, 95% CI; 1.076-2.301, p=0.019). The CIR and cumulative incidence of NRM tended to be higher in STM+ group than STM- group but with borderline significance (CIR, 5-year CIR 51.2% vs. 40.5%, HR 1.430, 95% CI 0.946-2.161, p=0.090; NRM, 5-year NRM 18.3% vs. 12.9%, HR 1.774, 95% CI 0.908-3.465, p=0.093). Among the 41 STM+ patients who achieved CR, those who received allogeneic HCT (n=15) showed better OS (5-year 40.0% vs. 11.5%) (HR;0.410, 95% CI;0.179-0.940, p=0.035), and relapse-free survival (5-year 40.0% vs. 7.7%) (HR;0.426, 95% CI;0.185-0.982, p=0.045) compared to those received consolidation chemotherapy only. Cumulative incidence of relapse was lower in the patients who received allogeneic HCT than who did not (5-year 33.3% vs. 61.5%) (HR;0.276, 95% CI;0108-0.708, p=0.007) while non-relapse mortality was similar between the two groups (HR;0.910, 95% CI;0.326-3.537, p=0.910) (Figure 1). In conclusion, the presence of STM is an independent adverse prognostic factor for AML, which can be overcome by allogeneic HCT.

Figure 1. Comparison of Overall survival (OS) (A), relapse-free survival (B), cumulative incidence of relapse (C), and cumulative incidence of non-relapse mortality (NRM) (D) according to the allogeneic hematopoietic cell transplantation (allogeneic HCT) in the secondary-type mutation positive (STM+) group patients. The effects of allogeneic HCT on OS and RFS are represented as Simon-Makuch plots.

Disclosures: Kim: AbbVie: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; AIMS Biosciense: Consultancy, Honoraria; Amgen: Consultancy, Honoraria; AML-Hub: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Astellas: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; BL & H: Research Funding; BMS & Celgene: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Boryung Pharm Co.: Consultancy; Daiichi Sankyo: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Janssen: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Handok: Consultancy, Honoraria; LG Chem: Consultancy, Honoraria; Novartis: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Pfizer: Consultancy, Honoraria; Pintherapeutics: Consultancy, Membership on an entity's Board of Directors or advisory committees; Sanofi Genzyme: Honoraria, Speakers Bureau; SL VaxiGen: Consultancy, Honoraria; VigenCell: Consultancy, Honoraria. Kim: Paladin: Consultancy, Honoraria, Research Funding; Pfizer: Honoraria; Novartis: Consultancy, Honoraria, Research Funding; Bristol-Meier Squibb: Research Funding.

*signifies non-member of ASH