Chronic lymphocytic leukemia (CLL) is highly heterogeneous, with patient survival ranging from a few months to several decades. Therefore, after the diagnosis of CLL, it is particularly important to conduct an accurate and comprehensive prognostic assessment for patients. At the 2024 American Society of Hematology (ASH) Annual Meeting held from December 7th to 10th, some research results on prognostic factors of CLL were announced. "Hematology Frontier" specially invited Dr. Shenmiao Yang from the Peking University Institute of Hematology, to select key studies from the conference and provide insightful commentary, aiming to offer valuable references and insights to colleagues in the field.

01: Complex Karyotype, but Not Isolated TP53 mutation, Predicts Overall Survival in Chronic Lymphocytic Leukemia Patients in the Era of Targeted Therapy

Abstract #583

02: IGHV Unmutated Status, Low Tumor Lysis Risk Disease and BRAF Mutated Status Are Predictors for Early MRD Responders Treated with MRD Defined Ibrutinib with Venetoclax: Report of the UK NCRI FLAIR Study

Abstract #585

03: Low Variant Allele Frequency (VAF) TP53 Mutation (mut) Is Not a Poor Prognostic Marker in CLL Patients Treated with Targeted Therapy

Abstract #587

Dr. Shenmiao Yang：These three abstracts provide valuable insights into prognostic factors for CLL. The key findings are summarized as follows:

1. TP53 Mutations: Abstract #587 highlights TP53 mutations as adverse prognostic factors for time to treatment initiation, treatment duration, and overall survival. The 2023 ASH meeting introduced a 10% VAF threshold for TP53 mutations, which Abstract #587 validates, showing that low-frequency mutations (5%–10%) do not indicate high risk.
2. Complex Karyotype (CK): Abstract #583 emphasizes CK as a stronger prognostic factor than TP53 abnormalities in the era of novel therapies. The study underscores the significance of genetic instability in defining high-risk CLL.
3. IGHV and BRAF Mutations: Abstract #585 demonstrates that IGHV unmutated status is associated with faster MRD negativity in patients treated with ibrutinib and venetoclax (I+V). Additionally, the study introduces BRAF mutations as a novel predictor, with mutation carriers achieving MRD negativity over five times faster than non-carriers.

The evolving treatment landscape for CLL continues to redefine high-risk disease. Ongoing research into novel prognostic markers and tailored therapeutic strategies remains critical for improving outcomes in high-risk patients.

Professor Shenmiao Yang Chief Physician, MD Peking University Institute of Hematology

Professional Appointments:

• Member, Lymphoma Group, Oncology Branch, Chinese Medical Association
• Member, Lymphocytic Disease Group, Hematology Branch, Chinese Medical Association
• Member, China Anti-Lymphoma Alliance, Clinical Oncology Collaboration Committee (CSCO), Chinese Anti-Cancer Association
• Member, Chronic Lymphocytic Leukemia Working Group, Hematologic Oncology Committee, Chinese Anti-Cancer Association
• Deputy Secretary-General, Malignant Lymphoma Working Committee, Hematology Branch, Chinese Society of Geriatrics
• Member, Lymphatic Hematology Committee, Chinese Geriatric Oncology Society

Expertise:

• Chronic lymphocytic leukemia (CLL)
• Malignant lymphoma

Key Contributions:

• Invited by IARC/WHO to co-author chapters on “CLL Epidemiology” and “Monoclonal B-Lymphocytosis (MBL)” in the 5th edition of the WHO Classification of Haematolymphoid Tumours.
• Contributor to the development of domestic guidelines and expert consensus in related fields.
• Delivered invited lectures at the International Workshop on Chronic Lymphocytic Leukemia (iwCLL) for two consecutive sessions.
• Interviewed by ASH News regarding CLL-related topics.
• Lead investigator in CLL and lymphoma studies, publishing extensively in these areas.