PO.CL12.03 · 临床研究

Evaluating the molecular landscape of genetic mutations among Black patients with acute myeloid leukemia

编号 5301 展板 21 时间 4/21 09:00–12:00 区域 Section 44 主讲 Eno-obong Udoh, BS

分会场 Epigenetics, Cytogenetics, and Clinical Molecular Genetics

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作者与单位

Eno-obong B. Udoh¹, Xiaoying (Nicole) Chen², Sarah J. Philip³, Yazeed Sawalha⁴, Yazan F. Madanat⁵, Ameera Rose⁶, Teodora Kuzmanovic⁶, John C. Molina⁷, Moaath K. Mustafa Ali⁷, Akriti G. Jain⁷, Abhay Singh⁷, Sophia Balderman⁷, Babal Kant Jha⁸, Ronald Sobecks⁷, Betty K. Hamilton⁷, Sudipto Mukherjee⁷, Aaron Gerds⁷, Hetty Carraway⁷, Jaroslaw P. Maciejewski⁸, Mikkael Sekeres⁹, Anjali Advani⁷

¹Cleveland Clinic Lerner College of Medicine, Cleveland, OH,²Department of Quantitative Health Sciences, Cleveland Clinic Lerner Research Institute, Cleveland, OH,³Division of Medical Oncology & Malignant Hematology, Houston Methodist Hospital, Houston, TX,⁴Division of Hematology, The Ohio State University, Columbus, OH,⁵Harold C. Simmons Comprehensive Cancer Center, UT Southwestern Medical Center, Dallas, TX,⁶Cleveland Clinic Foundation, Cleveland, OH,⁷Department of Hematology and Medical Oncology, Cleveland Clinic Taussig Cancer Institute, Cleveland, OH,⁸Department of Translational Hematology and Oncology Research, Cleveland Clinic Lerner Research Institute, Cleveland, OH,⁹Sylvester Comprehensive Cancer Center, University of Miami Miller School of Medicine, Miami, FL

摘要 Abstract

Introduction: Acute myeloid leukemia (AML) is an aggressive blood cancer driven by genetic changes that disrupt hematopoiesis. It is characterized by poor survival, with two-thirds of patients dying within 5 years. Non-Hispanic Black patients with AML have higher mortality rates compared to White patients despite favorable disease factors like low-risk cytogenetics and younger age. Risk stratification in AML has been greatly improved by the inclusion of tools such as next generation sequencing (NGS) in the prognostication of AML. However, little is known about the molecular landscape and prognostic relevance of mutations in Black patients with AML. This study characterizes the genetic profiles of Black patients with AML at the Cleveland Clinic. Method: This retrospective, single-center, cohort study included patients diagnosed with AML between 2002 and 2022. Clinical data were obtained from electronic medical records and stored securely. Molecular data were obtained from NGS platforms of genes frequently mutated in AML. Overall survival (OS) was limited to patients receiving intensive induction chemotherapy and estimated using Kaplan-Meier method. Results: Overall, there were 118 (9.34%) Black patients among our cohort of 1,264 AML patients. 55% of these patients were male and the median age at diagnosis was 62 years. Karyotype analysis revealed that majority (68%) of Black patients had an abnormal karyotype driven by trisomy 8 (23.0%), -7 or del (7q) (17.6%), or -5 or del (5q) (16.2%) abnormalities, of which the latter two represent adverse risk disease. Most of these patients (65%) were treated with intensive induction chemotherapy and of these 30% (n=23) underwent a bone marrow transplant. NGS was available for 49.1% (n = 58) of Black patients and revealed a predominance of mutations in genes involved in DNA methylation: DNMT3A (24%, n=14) and TET2 (21%, n=12). Median OS was 24 months (95% CI: 14-46months) with a 5-year OS rate of 27% (95% CI:18-40%), lower than the national average of 32.9%. Older age (>60), poor risk cytogenetics, non-intensive chemotherapy, TET2 , and ASXL1 were associated with worse survival in univariable analysis (p<0.05). Upon adjusting for prognostic variables, only poor risk cytogenetics remained significant (p=0.02). Conclusion: DNMT3A and TET2 mutations were most observed in Black patients with AML in this cohort at similar frequencies compared to population studies. These genes are observed in clonal hematopoiesis indicating early events in leukemogenesis. Their prognostic significance remains undefined but may inform future studies addressing outcome disparities through better risk stratification and the development of targeted therapies. Study limitations include small sample size, NGS availability and self-reported race/ethnicity. Comparative analysis with White patients and prospective studies with genetic ancestry testing are needed.

利益披露 Disclosure

E. B. Udoh, None.. X. Chen, None.. S. J. Philip, None. Y. Sawalha, BeiGene ). Genmab ). AbbVie ). ADC Other, Consulting. Genmab Other, Consulting. Genentech Other, Honorarium. Y. F. Madanat, None.. A. Rose, None.. T. Kuzmanovic, None. J. C. Molina, Autolus g., Board of Directors, non-salaried role), Other, Consultancy, Honoraria. Jazz g., Board of Directors, non-salaried role), Other, Consultancy, Honoraria. Amgen Other, Consultancy, Honoraria. Sobi Other, Consultancy, Honoraria. AstraZeneca Other, Consultancy, Honoraria. M. K. Mustafa Ali, None. A. G. Jain, Takeda g., Board of Directors, non-salaried role). Novartis g., Board of Directors, non-salaried role), Other, Consultancy. Sobi g., Board of Directors, non-salaried role). Servier g., Board of Directors, non-salaried role). Geron Other, Speaking. Rigel Other, Speaking. A. Singh, None.. S. Balderman, None.. B. K. Jha, None. R. Sobecks, CareDx g., Board of Directors, non-salaried role). B. K. Hamilton, None.. S. Mukherjee, None.. A. Gerds, None.. H. Carraway, None.. J. P. Maciejewski, None. M. Sekeres, Bristol Myers Squibb g., Board of Directors, non-salaried role), ). Kurome g., Board of Directors, non-salaried role). Schroedinger g., Board of Directors, non-salaried role). A. Advani, Amgen ). MD Education Other, Honoraria. Pfizer ), Other, Manuscript help, honoraria/consulting. AstraZeneca Other, Honoraria, Consulting. Glycomimetics ). BEAM ). OBI ). Incyte ). Immunogen ). Seattle Genetics ). Macrogenics ). Servier ). Kura ). Novartis ), Other, Consultancy. Emmes Other, Honoraria. PER Other, Honoraria. WebMD Other, Honoraria. Wolters Kluwer Other, Honoraria. Kite ), Other, Consultancy. MJH Life Other, Honoraria.

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