Editor’s Note: From December 7–10, 2024, the 66th Annual Meeting of the American Society of Hematology (ASH) took place in San Diego, USA, gathering leading global experts to discuss the latest advancements in hematology. At this year’s conference, Dr. Haiwen Huang’s team from The First Affiliated Hospital of Soochow University presented three impactful studies through poster sessions (P1676, P3113, P4442). Hematology Frontier invited Professor Huang to share their insights and the clinical implications of these studies directly from the ASH venue.

Key Highlights

1. A phase II clinical trial replacing doxorubicin with liposomal mitoxantrone in the CMOP±R regimen demonstrated reduced cardiac toxicity while maintaining efficacy comparable to the R-CHOP regimen for first-line NHL treatment.
2. A retrospective analysis of NK/T-cell lymphoma revealed that most tumors localized to the nasopharynx, with late-stage disease linked to worse outcomes. Combining asparaginase with novel targeted drugs shows promise for enhanced efficacy.
3. For advanced high-risk NK/T-cell lymphoma, patients achieving complete remission (CR) may benefit from autologous stem cell transplantation (ASCT), while those without CR might require allogeneic transplantation.

Hematology Frontier: At this ASH meeting, your three studies focused on first-line treatment strategies for non-Hodgkin lymphoma (NHL) and clinical features and transplant approaches for extranodal NK/T-cell lymphoma (ENKTL). To start, how does the CMOP±R regimen compare to traditional therapies, and what breakthroughs or advantages does it offer?

Dr. Haiwen Huang:This phase II clinical trial focuses on developing more effective treatment regimens for NHL patients. While the CHOP regimen remains a widely accepted standard, doxorubicin’s well-documented cardiac toxicity poses limitations. Liposomal mitoxantrone, approved for treating relapsed/refractory T-cell lymphoma, offers a potential alternative with reduced toxicity.

The trial evaluates the efficacy of replacing doxorubicin with liposomal mitoxantrone in the CMOP±R regimen for first-line NHL treatment. Preliminary findings reveal no significant cardiac toxicities among participants. The objective response rate (ORR) reached an impressive 96.8%, with a complete response (CR) rate exceeding 77%.

We also conducted a matching-adjusted indirect comparison (MAIC) with data from the POLARIX trial for the R-CHOP regimen. The analysis indicated that the CMOP±R regimen delivers comparable efficacy. Notably, 51.2% of our cohort consisted of high-risk cases (IPI scores of 3–5), and the CMOP±R regimen demonstrated similar efficacy in this subgroup compared to R-CHOP.

The primary advantage of integrating liposomal mitoxantrone into the regimen is its significantly reduced cardiac toxicity. Additionally, the efficacy metrics show that this approach is not inferior to R-CHOP.

Hematology Frontier: Your two studies on extranodal NK/T-cell lymphoma (ENKTL) examined the clinical features and treatment strategies for this rare disease. Could you elaborate on the prospects for combining novel agents with stem cell transplantation, and how treatment should be individualized to enhance efficacy while minimizing adverse effects?

Dr. Haiwen Huang: Our retrospective analysis of ENKTL cases over the past decade at our center revealed several key findings. Most tumors were localized to the nasopharynx, with later stages associated with worse outcomes. Of particular note, advanced-stage patients with bone marrow involvement exhibited significantly higher rates of EBV positivity.

In terms of treatment, asparaginase remains a cornerstone in first-line therapy. However, when combined with novel agents such as PD-1 inhibitors and HDAC inhibitors like chidamide, treatment outcomes improve significantly.

For high-risk advanced-stage patients, consolidation with transplantation is critical for improving survival. Our study found that for patients who achieved complete remission (CR), autologous stem cell transplantation (ASCT) was sufficient. While current guidelines do not provide definitive recommendations for choosing between ASCT and allogeneic stem cell transplantation (allo-HSCT), our data suggest that for patients receiving novel agents and achieving CR, ASCT may suffice. Allo-HSCT, on the other hand, showed no additional efficacy and was associated with higher toxicity. However, for patients failing to achieve CR, allo-HSCT may provide a better chance of long-term survival.

Ultimately, ENKTL treatment strategies should be stratified based on disease stage and risk. For advanced-stage patients or those with bone marrow involvement, ASCT is recommended for consolidation. For high-risk patients not achieving CR, allo-HSCT may offer superior outcomes despite its higher toxicity profile.

Hematology Frontier: These three studies provide valuable insights into lymphoma treatment, but there is often a gap between research findings and widespread clinical application. How do you think we can ensure that more patients benefit in the future?

Dr. Haiwen Huang:The two studies on NK/T-cell lymphoma relied on retrospective analysis, drawing on real-world clinical data to reveal specific characteristics and treatment patterns of the disease.

Regarding the CMOP±R regimen for first-line treatment, the results presented here come from a Phase II clinical trial. However, it is important to acknowledge the inherent limitations of Phase II data in terms of evidence strength. To address this, we have already initiated a Phase III clinical trial to further validate and strengthen the current findings. If the Phase III trial confirms the significant efficacy of the CMOP±R regimen, the evidence level for this treatment strategy will be markedly elevated. This would provide clinicians with more robust and reliable guidelines to inform clinical decisions, ultimately translating research findings into real-world benefits for patients.

First Affiliated Hospital of Soochow University

• MD, Chief Physician, Professor, and PhD Supervisor
• Head of the Lymphoma Unit, First Affiliated Hospital of Soochow University

Professional Roles and Memberships:

• Member, Lymphocyte Diseases Subgroup, Hematology Branch, Chinese Medical Association
• Member, Lymphatic Hematology Group, Oncology Branch, Chinese Medical Association
• Member, Lymphoma Quality Control Expert Committee, National Cancer Center
• Expert Reviewer for Doctoral and Master’s Theses, Ministry of Education
• Vice Chair, Lymphoma Professional Committee, Chinese Medical Education Association
• Standing Member, Integrative Medicine Lymphoma Committee, Chinese Anti-Cancer Association
• Deputy Head, Lymphoma Group, Hematology Branch, Jiangsu Medical Association
• Standing Member, Lymphoma Professional Committee, Jiangsu Anti-Cancer Association

Training and International Experience:

• 2005–2006: Research Assistant, Faculty of Medicine, University of Hong Kong
• 2006–2007: Resident Physician, University Hospital of Montpellier, France; Qualified Specialist in Hematology, France
• 2009–2010: Senior Visiting Scholar, University Hospital of Montpellier, France
• August–October 2013: Visiting Scholar, University of California, Los Angeles (UCLA), USA

Awards and Honors:

• 2023 Distinguished Contribution Award in Lymphoma Field, “People’s Good Doctor”
• Recognized under Jiangsu Province’s “Six Talent Peaks” Program

Research and Academic Contributions:

• Principal investigator or participant in multiple national and provincial natural science foundation projects
• Published over 20 SCI-indexed papers
• Peer Reviewer for Chinese Journal of Hematology, Annals of Hematology, and Hematology Oncology journals