ASH News Flash | Professor Huanling Zhu Highlights Breakthrough Leukemia Studies

The 2025 Annual Meeting of the American Society of Hematology (ASH) was held from December 6–9 in Orlando, USA, drawing global attention as one of the most influential international conferences in hematology. To deliver first-hand updates from the meeting, Oncology Frontier – Hematology Frontier launched the special series “ASH Today: News Flash”, connecting directly with on-site experts.

On the opening day of ASH 2025, we were honored to invite Huanling Zhu, Professor at West China Hospital of Sichuan University, to share the most impactful leukemia research highlights presented on Day 1 of the conference.

Expert Perspective: Key Leukemia Advances from ASH 2025

Professor Huanling Zhu: “Two studies in the leukemia field stood out prominently today at ASH. One examined the impact of myeloid somatic mutations at diagnosis on treatment outcomes in chronic-phase chronic myeloid leukemia (CML). The other validated measurable residual disease (MRD) as a surrogate endpoint in acute myeloid leukemia (AML). I will walk you through the core findings and their clinical implications.”

Impact of Myeloid Somatic Mutations at Diagnosis in Chronic-Phase CML

First Analysis from the iCMLf Genomics Alliance

Publication Number: 75

Title: Somatic mutations at diagnosis in patients with chronic-phase CML receiving frontline imatinib are associated with a higher rate of treatment failure: First analysis from the International CML Foundation (iCMLf) Genomics Alliance on the HARMONY platform

Study Background

Increasing evidence suggests that somatic myeloid gene mutations beyond BCR::ABL1 at CML diagnosis are associated with treatment failure. Genomic analyses of unselected chronic-phase CML cohorts show mutation rates of 17–24%, with ASXL1 being the most common (7.3–9%).

Although next-generation sequencing (NGS) is widely used in hematologic malignancies, genomic profiling at CML diagnosis has not yet been incorporated into standard risk stratification. The iCMLf Genomics Alliance, leveraging the HARMONY Alliance platform, aims to address this gap by integrating large international datasets.

Methods

Data from 468 newly diagnosed chronic-phase CML patients treated with frontline imatinib were analyzed. Genomic data were collected from 12 international centers across Europe, the Middle East, Australia, Asia, and North America. Outcomes included overall survival (OS), progression-free survival (PFS), and failure-free survival (FFS), defined according to ELN 2020 criteria.

Key Results

20.5% (96/468) of patients harbored pathogenic myeloid mutations at diagnosis
ASXL1 was the most frequent mutation (11.3%)
Median follow-up: 4.2 years

Survival outcomes:

OS: no significant difference between mutation and non-mutation groups
5-year PFS: 76.3% vs 83.1% (P=0.041)
5-year FFS: 43.8% vs 65.2% (P<0.0001)

Patients with ASXL1 mutations had the lowest 5-year FFS (41.0%), significantly worse than other mutation carriers and mutation-negative patients.

Conclusion

This is the largest genomic analysis to date in frontline imatinib-treated CML. Pathogenic myeloid mutations at diagnosis—particularly ASXL1—are associated with inferior PFS and FFS, supporting the integration of genomic data into CML risk stratification and management.

Validation of MRD as a Surrogate Endpoint in AML

A Large-Scale HARMONY Alliance Study

Publication Number: 343

Title: Validation of measurable residual disease as a surrogate endpoint in acute myeloid leukemia: A HARMONY Alliance study of European randomized trials

Study Rationale

MRD before consolidation therapy is a powerful prognostic marker in AML. Beyond prognosis, MRD increasingly guides treatment decisions. Establishing MRD as a regulatory surrogate endpoint—as recently approved by the FDA in multiple myeloma—could significantly accelerate AML drug development.

Methods

This pooled analysis included 1,858 adult AML patients from seven prospective randomized phase II/III trials conducted by European cooperative groups. MRD was assessed after two chemotherapy cycles using:

Multiparameter flow cytometry (MFC)
qPCR for NPM1 mutations

Analyses evaluated MRD at:

Individual level (association with OS)
Trial level (correlation between treatment effects on MRD and OS)

Key Results

MRD positivity was strongly associated with inferior OS HR 1.66 (95% CI: 1.33–2.07; P<0.001)
Overall OS odds ratio for MRD negativity: 0.39
In non-transplanted patients, trial-level surrogate strength was very high (R² = 0.99)

Conclusion

This represents the largest MRD dataset in AML to date. Post-induction MRD is a robust predictor of OS and demonstrates strong surrogate validity—particularly in non-transplanted patients—supporting its use as an intermediate endpoint in AML clinical trials.

Summary

ASH 2025 delivered two landmark advances in leukemia precision medicine:

CML: Diagnostic myeloid somatic mutations—especially ASXL1—significantly impact long-term treatment outcomes, paving the way for genomics-based risk stratification.
AML: Large-scale validation confirms MRD as a powerful prognostic and surrogate endpoint, offering strong support for its regulatory acceptance in future drug development.

Together, these studies deepen our understanding of leukemia biology and provide actionable guidance for clinical decision-making and trial design.