ASH Roundtable | Prof. Zhang Huilai’s Team: New Frontiers and Clinical Breakthroughs in Lymphoma Therapy

The 67th Annual Meeting of the American Society of Hematology (ASH) was held grandly in Orlando from December 6 to 9, 2025, bringing together the latest research and clinical advances from the global hematology community. At this year’s meeting, multiple studies from the team led by Professor Zhang Huilai of Tianjin Medical University Cancer Institute and Hospital were selected for presentation, including one oral presentation. These studies comprehensively showcased the latest progress in lymphoma treatment, spanning aggressive and indolent lymphomas, dual-target allogeneic CAR-T cell therapies, and several innovative combination strategies. On site, Hematology Frontier invited Dr. Yu Jingwei, Dr. Li Wei, and Professor Zhao Peiqi to participate in a roundtable discussion to provide in-depth interpretation of these studies, explore the clinical value of novel therapeutic strategies, discuss key considerations in patient selection and management, and outline future treatment trends, offering valuable insights and practical references for clinicians and researchers in the lymphoma field.

Hematology Frontier: At this ASH meeting, you reported a phase I study of Lucar-G39D, a novel anti-CD19/CD20 dual-target allogeneic γδ T-cell therapy. Could you introduce the innovative aspects of this platform and its potential advantages in relapsed/refractory B-cell non-Hodgkin lymphoma (B-NHL)?

Dr. Yu Jingwei: This product is the world’s first dual-target universal CAR-T cell therapy developed on a γδ T-cell platform. It is designed to address key challenges associated with conventional autologous CAR-T therapy, including long manufacturing times, high costs, and disease progression in some patients during cell preparation. Universal CAR-T products are off-the-shelf and amenable to large-scale manufacturing, which can significantly reduce treatment costs and may enable broader and more accessible clinical application in the future.

In the phase I dose-escalation study reported at this meeting, the overall response rate reached 75%, with a complete response rate of approximately 40%. With further dose expansion and eventual determination of the optimal dosing regimen, overall efficacy is expected to improve further, potentially achieving higher complete response rates.

Hematology Frontier: You also shared real-world Chinese data on the Pola-Hi-CHP regimen in newly diagnosed diffuse large B-cell lymphoma (DLBCL). How do its efficacy and safety in real-world practice compare with clinical trial results?

Dr. Li Wei: Currently, Pola-R-CHP is the standard treatment for patients with intermediate- to high-risk newly diagnosed DLBCL, yet some patients still have poor outcomes, highlighting the need to further improve efficacy. In this context, we replaced the imported CD20 antibody rituximab with the domestically developed, first-in-class innovative antibody zanubrutinib-based antibody Hi. In a phase III registration study, the Hi-CHOP regimen significantly improved complete response rates compared with R-CHOP, demonstrating clear therapeutic potential.

In our study, more than half of the enrolled patients had stage III–IV disease, indicating a relatively poor prognosis. The Pola-Hi-CHP regimen achieved a complete response rate of 83.3% and an objective response rate of 100% in the overall population. Subgroup analyses showed a complete response rate of 84.6% in patients with stage III–IV disease, 89.1% in patients with an IPI score of 0–3, and 88.2% in patients with double-expressor lymphoma. These results suggest that this combination of international and domestic innovation may compensate for limitations of existing therapies and provide better treatment options for a broad DLBCL population.

Hematology Frontier: In the ZAP trial, zanubrutinib combined with G-CHOP demonstrated encouraging efficacy in high-risk follicular lymphoma (FL), particularly among early molecular responders. Could you describe the study design and key findings?

Professor Zhao Peiqi: Follicular lymphoma generally has a favorable prognosis, with a median survival of 14 to 18 years. However, a substantial proportion of intermediate- to high-risk patients experience disease progression within two years. We therefore explored an intensified treatment strategy based on standard G-CHOP to further improve outcomes in this population. Previous studies showed that obinutuzumab combined with zanubrutinib achieved an overall response rate of 69% and a complete response rate of 39%, providing the rationale for incorporating zanubrutinib into induction therapy.

Early data indicated that patients achieving MRD negativity at cycle 2 almost universally became PET-CT negative by cycle 4. Our goal was to achieve early molecular remission to shorten treatment duration and maintenance therapy. MRD, as a microscopic indicator of disease response, can detect relapse or progression earlier than imaging modalities such as PET-CT and thus served as a key guiding strategy in this study.

Results showed a one-year progression-free survival rate of 97%, with only one progression event among 32 patients within the first year. These findings suggest that intensified induction therapy combined with response-adapted de-escalated maintenance can improve prognosis while maintaining safety. Given the small sample size and limited follow-up, larger studies with longer follow-up are needed for further validation.

Hematology Frontier: In the Compass phase II study, you evaluated the novel CMOEP regimen, based on liposomal mitoxantrone, as first-line therapy for peripheral T-cell lymphoma (PTCL). Could you share the preliminary efficacy and safety results and its advantages over traditional regimens?

Dr. Yu Jingwei: PTCL is a highly aggressive and heterogeneous disease, and standard first-line treatment with CHOP or CHOP-like regimens yields suboptimal outcomes. Based on favorable data from earlier studies of liposomal mitoxantrone monotherapy in relapsed/refractory PTCL, we designed a phase I study replacing doxorubicin with liposomal mitoxantrone to create the CMOEP regimen. This study demonstrated remarkable efficacy, with an overall response rate of 100% and a complete response rate of approximately 70%.

Building on these results, we initiated a multicenter phase II study across 16 centers nationwide, aiming to enroll 78 patients. Nearly 40 patients have been enrolled to date. At ASH, we reported preliminary data from approximately 20 patients, which reproduced the favorable safety and tolerability observed in phase I. The overall response rate was 94.7%, with a complete response rate of 68.4%. Among patients evaluated by PET-CT, the overall response rate was 100% and the complete response rate was 87.5%. As enrollment continues, we expect to further confirm the efficacy and safety observed in phase I, with the goal of improving both short-term response and long-term survival in PTCL, particularly in poor-prognosis subtypes.

Hematology Frontier: In Chinese clinical practice, what are the most critical management strategies or challenges when using polatuzumab vedotin–based regimens for newly diagnosed DLBCL, particularly regarding patient selection and adverse event management?

Dr. Li Wei: Current studies on polatuzumab vedotin in first-line DLBCL mainly focus on patients with an International Prognostic Index score of 0 to 1. The key issue is whether polatuzumab vedotin should be used in this group and which patients are most suitable. An IPI score of 0 to 1 does not exclude adverse prognostic factors such as double expression or TP53 mutations.

Therefore, further risk stratification is required in these patients. For those with an IPI score of 0 to 1 and no additional adverse factors, standard R-CHOP remains the preferred option, and polatuzumab vedotin may not be necessary. However, in the presence of adverse prognostic features, multicenter data from Chinese studies suggest that Pola-R-CHP can be considered as initial therapy. The extent of its benefit over standard R-CHOP still requires validation in larger cohorts.

Hematology Frontier: Based on the Trium study and real-world data in elderly Hodgkin lymphoma, what insights do MRD-guided triple regimens or BV/PD-1 inhibitor combinations offer for clinical practice? Could these approaches change future treatment standards?

Professor Zhao Peiqi: Mantle cell lymphoma is relatively rare and biologically indolent yet aggressive. Current treatment strategies include CD20 monoclonal antibodies combined with autologous stem cell transplantation and maintenance therapy, but many patients cannot tolerate high-intensity regimens. In the earlier POLARIS study, we evaluated a regimen combining a CD20 monoclonal antibody with a BTK inhibitor and lenalidomide, achieving a two-year progression-free survival rate of 85%. However, many enrolled patients were low- or intermediate-risk.

The Trium study further optimized this strategy by evaluating a combination of a CD20 monoclonal antibody, a BTK inhibitor, and Sonrotoclax, a BCL-2 inhibitor, in a population enriched with high-risk features such as intermediate- to high-risk MIPI scores, Ki-67 ≥30%, or TP53 mutations. Current results are highly encouraging. Among ten patients who completed six cycles of therapy, eight achieved complete response and one achieved partial response, with favorable safety. All evaluable patients achieved MRD negativity, indicating deep remission. Sonrotoclax appears to offer improved tolerability and efficacy compared with venetoclax, although longer follow-up is needed.

In elderly Hodgkin lymphoma, we conducted a retrospective analysis of 493 patients treated at 13 centers nationwide between 2008 and 2023. Despite its low incidence, elderly HL has a five-year survival rate of only 50%, far lower than in younger patients, largely due to comorbidities and lack of standardized treatment. Our analysis showed that combining PD-1 inhibitors or brentuximab vedotin with traditional chemotherapy significantly improved outcomes. Elderly HL patients also had a higher proportion of mixed cellularity subtype, which contributes to poorer prognosis. Through this large retrospective study, we aim to clarify subtype distribution, historical treatment patterns, and survival outcomes in Chinese elderly HL patients and plan prospective studies to further improve outcomes in this population.