Editor's Note: The 66th Annual Meeting of the American Society of Hematology (ASH) was held from December 7–10, 2024, in San Diego, USA. This prestigious gathering brought together global experts and scholars to discuss the latest advancements in hematology. At this year's conference, the Tianjin Medical University Cancer Institute and Hospital's lymphoma team presented 6 significant research studies. As part of the Hematology Frontier series, Dr. Huilai Zhang, the team leader, connected live from a domestic studio with her team on-site in the United States. Together, they delved into their findings, shared insights, and exchanged perspectives, bridging international and domestic expertise. Below is a detailed summary of their discussions, aimed at providing valuable guidance for clinical practice.
  • Dr. Huilai Zhang：“At this very moment, hematology experts and scholars from around the globe are convening to share and discuss the latest research and clinical developments in our field. We are honored that the lymphoma team from Tianjin Medical University Cancer Institute and Hospital has had six research projects selected for presentation this year—one oral presentation and five poster sessions. Today, I will connect with our researchers, currently at the ASH conference venue, to provide an in-depth overview of these studies for our colleagues. To begin, could you briefly introduce the atmosphere and highlights of the ASH meeting?”
  • Dr. Peiqi Zhao ：“Hello, everyone. Greetings from the ASH conference venue here in San Diego. The ASH Annual Meeting has always been a pivotal event in the field of hematologic malignancies. This year, the conference is more spectacular than ever, with over 30,000 experts and scholars attending from around the world. The event features more than 100 specialized sessions, focusing on the latest advancements and future trends in the field.
  • On the first day, we witnessed groundbreaking research on bispecific antibody therapies, cellular therapies, and novel drug developments. These studies have provided profound insights, significantly enhancing our understanding of treatment strategies for hematologic malignancies. Additionally, we’ve had the opportunity to engage in meaningful discussions with experts from various regions, exchanging perspectives on pressing challenges and innovations in the field.
  • Under the leadership of Dr. Huilai Zhang, our lymphoma team has prepared thoroughly for this conference, presenting both oral and poster sessions. We deeply appreciate the ASH platform for enabling such vibrant exchanges, fostering collaboration and progress.”
  • Dr. Zheng Song ：“At this year’s ASH meeting, I presented a national multicenter clinical study on the combination of zanubrutinib and lenalidomide for patients with relapsed/refractory diffuse large B-cell lymphoma (R/R DLBCL), known as the BGB-3111-110 study. Led by Dr. Huilai Zhang, this is an open-label, phase I clinical trial featuring dose-escalation and expansion cohorts.
  • The study enrolled 66 patients, the majority of whom were in advanced stages (III/IV). Over 40% were primary refractory cases, and more than half had high-risk factors. During the dose-escalation phase, three lenalidomide dosage levels—15 mg, 20 mg, and 25 mg—were tested, with no dose-limiting toxicities observed. Consequently, in the expansion phase, patients received lenalidomide 25 mg once daily in combination with zanubrutinib 160 mg twice daily.
  • From a safety perspective, 74% of patients experienced grade ≥3 treatment-emergent adverse events (TEAEs), with hematological toxicities being the most common. These were typically manageable with supportive care or temporary treatment suspension. Regarding efficacy, the overall response rate (ORR) across all patients was 50%, with a complete response (CR) rate of 35%. In the expansion cohort, the ORR increased to 58%, and the CR rate reached 42%.
  • These outcomes demonstrate promising response rates for R/R DLBCL patients, comparable to or even exceeding those achieved with internationally established regimens, such as polatuzumab vedotin plus BR or lenalidomide combined with tafasitamab. Importantly, the zanubrutinib-lenalidomide combination also showed a favorable safety profile. This suggests that it may offer an effective, convenient, and well-tolerated therapeutic option for patients with R/R DLBCL, potentially providing longer-lasting remissions.”
  • Dr. Wen Gao ：“My presentation focused on a study investigating neurological toxicities associated with blinatumomab in real-world settings. Blinatumomab, a bispecific antibody targeting CD19 and CD3, has shown remarkable potential as an anti-tumor therapy for hematologic malignancies. However, adverse events like cytokine release syndrome (CRS) and neurological toxicities have raised significant clinical concerns. Unfortunately, there has been limited research on these side effects.
  • To address this, we analyzed data from the U.S. Food and Drug Administration’s Adverse Event Reporting System (FAERS), covering reports from October 1, 2014, to September 30, 2023. Using multiple algorithms—including ROR, BCPNN, and MGPS—we conducted an in-depth analysis of 5,962 patient cases.
  • Our findings revealed a higher incidence of fatal neurological toxicities in younger patients. Additionally, co-administration of certain drugs, particularly those targeting the genitourinary or musculoskeletal systems, appeared to elevate the risk of such events. These results underscore the importance of vigilant monitoring for neurological toxicities, especially in younger patients or those receiving concomitant medications. By enhancing early detection and intervention, we can ensure safer clinical use of blinatumomab.”
  • Dr. Yaxiao Lu: “At the ASH conference, we deeply felt the vibrant academic atmosphere. I am excited to share our center’s research findings on how PIM1 gene mutations promote the membrane localization of the ANXA2 gene, thereby enhancing the molecular mechanisms underlying the pathogenesis of diffuse large B-cell lymphoma (DLBCL).
  • As we know, DLBCL is a highly heterogeneous disease, with the biological characteristics of tumor cells playing a critical role in clinical outcomes and prognosis. Previously, our center discovered that PIM1 gene mutations are relatively common in DLBCL, occurring in approximately 28.4% of cases. Through multicenter external data studies, we also found that patients with PIM1 mutations have worse prognoses, making it an independent adverse prognostic factor for overall survival (OS). This prompted us to investigate why PIM1 mutations lead to poorer outcomes and which key mutation sites are involved.
  • In a larger patient cohort study, we identified four major PIM1 mutation sites: P81S, E135K, S97N, and L184F. Among them, patients with the L184F mutation had the worst prognosis. Subsequent in vitro experiments showed that PIM1 mutations significantly enhanced tumor cell proliferation, while in vivo animal experiments demonstrated that mice carrying PIM1-mutated tumors had larger tumor volumes.
  • To explore the mechanisms behind the increased tumor aggressiveness caused by PIM1 mutations, we conducted transcriptomic sequencing, which revealed activation of the PI3K/AKT signaling pathway. To further clarify this activation mechanism, we performed proteomic analysis and discovered that PIM1 mutations interact with the ANXA2 gene, promoting its translocation from the cytoplasm to the cell membrane, thereby increasing its activity. Furthermore, activated ANXA2 binds to TLR4, triggering downstream activation of the PI3K/AKT/mTOR pathway.
  • Clinically, using a high-throughput drug screening platform, we identified multiple PI3K inhibitors with high sensitivity in PIM1-mutated patients. Notably, the combination of PIM1 inhibitors and PI3K inhibitors demonstrated synergistic effects, suggesting a promising therapeutic strategy for patients with PIM1 mutations. This concludes my introduction to our research.”
  • Dr. Peiqi Zhao: “The study I am presenting focuses on a real-world analysis of the Pola-R-CHP regimen in DLBCL, based on multicenter data from China. We screened and included data from 131 patients who received Pola-R-CHP treatment for this research.
  • The POLARIX trial previously established that compared to the traditional R-CHOP regimen, Pola-R-CHP improved two-year progression-free survival (PFS) by 6.5% and three-year PFS by 7.7%. At this year’s ASH meeting, the five-year PFS data was released, showing a 5.1% improvement. However, the POLARIX trial enrolled a relatively homogeneous patient population with few comorbidities and good overall health. In contrast, real-world data reflect more diverse and complex patient profiles.
  • In our study, with a median follow-up period of 12 months, the one-year PFS in the Pola-R-CHP group reached 90.1%, compared to 84.3% in the R-CHOP group. Although the difference did not reach statistical significance, survival curves showed a clear separation, indicating potential clinical benefits of Pola-R-CHP.
  • Subgroup analysis revealed that in high-risk groups, such as patients with advanced Ann Arbor stage III/IV disease, non-germinal center B-cell (Non-GCB) subtypes, and those with multiple extranodal involvements, Pola-R-CHP outperformed R-CHOP. Currently, no significant difference in overall survival (OS) has been observed between the two groups, and their safety profiles were comparable.
  • Additionally, we performed genetic testing on 96 patients, finding that 25% had the MCD subtype, 13% had the EZB subtype, and approximately 30% had unclassified risk types. Patients with the MCD subtype generally had poorer prognoses, while those with the EZB subtype exhibited relatively favorable outcomes, with both ORR and CRR nearing 100%.
  • We also observed a relatively high proportion of high-risk genetic mutations among the patients. Specifically, 48% had PIM1 mutations, and 36% had TP53 mutations. Notably, even among patients with TP53 mutations, Pola-R-CHP achieved an ORR of 82% and a CRR of 70%. For PIM1-mutated patients, the CRR was 76%, and the ORR was as high as 88%.
  • Overall, genetic mutations, including TP53 and PIM1, remain significant factors contributing to poor prognosis. Importantly, 8% of patients experienced disease progression despite Pola-R-CHP treatment. This finding highlights the need for more precise patient assessments before initiating treatment. For patients with suboptimal short-term outcomes, timely adjustments to the treatment regimen should be considered, such as combining bispecific antibodies, CAR-T therapy, or multidisciplinary consultations to develop more personalized treatment plans. Encouraging patient participation in new clinical trials is also a viable approach to improving outcomes for these refractory cases. Thank you for listening to my presentation.”
  • Dr. Huilai Zhang: “Thank you to our four team members for their outstanding presentations and personal insights. These studies represent some of the exploratory efforts by our team in the field of lymphoma. We hope these findings will contribute to the progress of global lymphoma research.
  • The lymphoma department at Tianjin Medical University Cancer Institute and Hospital focuses on four main research areas: follicular lymphoma, mantle cell lymphoma, extranodal lymphomas, and immune evasion. We actively promote precision diagnostics, clinical research on new drugs and technologies, and aim to achieve refined, precise, and comprehensive management of lymphoma patients. By expanding collaborations with outstanding domestic and international teams, we strive to accelerate the translation of research findings into clinical practice, achieving sustained development in clinical research. Ultimately, we aim to benefit more lymphoma patients and contribute to the implementation of health initiatives in China.

Profiles of the Tianjin Tumor Hospital Lymphoma Team

Dr. Huilai Zhang

Institution: Tianjin Medical University Cancer Institute and Hospital Title: PhD in Oncology, Chief Physician, Doctoral Supervisor, Director of the Department of Lymphoma

Research Focus:

  • Molecular diagnosis and personalized treatment of malignant lymphomas

Academic and Professional Roles:

  • Member of the National Cancer Center Lymphoma Quality Control Expert Committee
  • Council Member of the 9th Executive Committee of the Chinese Anti-Cancer Association
  • Deputy Chair of the Lymphoma Committee of the Chinese Anti-Cancer Association
  • Standing Committee Member of the CSCO Lymphoma Expert Committee
  • Member of the Lymphoma Group of the Oncology Branch of the Chinese Medical Association
  • Chair of the Tumor Clinical Chemotherapy Committee of the Tianjin Anti-Cancer Association
  • Chair of the Lymphoma Committee of the Tianjin Integrative Medicine Association
  • Deputy Chair of the Hematology Quality Control Center of Tianjin
  • Vice Chair of the Hematology Physician Branch of the Tianjin Medical Association

Recognitions and Awards:

  • Selected for Tianjin’s Second Batch of High-Level Health Industry Talent Program
  • Participant in the Tianjin Medical University “123 Clinical Talent Development Program”
  • Recipient of the 2023 Tianjin Medical University Outstanding Graduate Supervisor Award
  • Awards include the Third Prize of the Chinese Medical Science and Technology Award, a Popular Science Award from the Chinese Anti-Cancer Association, and multiple prizes for scientific and technological advancement in Tianjin.

Publications and Editorial Roles:

  • Published over 90 papers as first or corresponding author in journals such as Blood, Cancer Research, J Exp Med, Leukemia, CTM, AJH, and BJH.
  • Serves as Associate Editor of Oncology Pharmacy and Editorial Board Member for journals including Blood Research, Hematological Oncology, and Leukemia & Lymphoma.
  • Recipient of the “National Outstanding Physician” Award.
Dr. Peiqi Zhao

Institution: Tianjin Medical University Cancer Institute and Hospital Title: PhD in Medicine, Associate Chief Physician

Research Focus:

  • Medical treatment, basic, and clinical research in lymphoma

Academic and Professional Roles:

  • Principal Investigator of a National Natural Science Foundation project
  • Published over 20 SCI articles
  • Contributed as a committee member or expert writer to CSCO and CACA lymphoma diagnosis and treatment guidelines

Affiliations:

  • Member of the Tumor Internal Medicine Committee of the Chinese Medical Promotion Society
  • Member of the Lymphoma Professional Committee of the Chinese Association for Elderly Healthcare
  • Standing Committee Member of the Lymphoma Immunotherapy Committee of the Beijing Cancer Prevention Society
  • Committee Member of the Tianjin Anti-Cancer Association’s Lymphoma and Clinical Chemotherapy Committees
Dr. Zheng Song

Institution: Tianjin Medical University Cancer Institute and Hospital Title: Associate Chief Physician

Professional Roles and Affiliations:

  • Member of the Youth Committee of the National Lymphoma Quality Control Expert Committee
  • Committee Member of the Lymphoma Rehabilitation and Integration Professional Committee of the Chinese Anti-Cancer Association
  • Committee Member of the Lymphoma Professional Committee of the Chinese Association for Elderly Healthcare
  • Secretary of the Lymphoma Committee of the Tianjin Anti-Cancer Association
  • Visiting Scholar at Moffitt Cancer Center, USA
Dr. Wen Gao

Institution: Tianjin Medical University Cancer Institute and Hospital Title: PhD Candidate, Attending Physician

Research Focus:

  • Cardiac remodeling, heart failure, and toxicities of anti-tumor drugs

Academic Contributions:

  • Principal Investigator of multiple provincial and municipal research projects
  • Published over 10 SCI articles

Affiliations:

  • Deputy Chair of the Cardiovascular Disease Prevention Committee of the Jinan Preventive Medicine Association
  • Committee Member of the Cardiac Critical Care and Arrhythmia Committees in Jinan Medical Associations
Dr. Yaxiao Lu

Institution: Tianjin Medical University Title: PhD in Oncology

Research Focus:

  • Basic and clinical research in malignant lymphomas

Academic Achievements:

  • Published six papers as first or co-first author in journals including CTM, AJH, and Cancer Research
  • Recipient of National Scholarship and Tianjin Medical University Outstanding Graduate Award.
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Last updated on 2024.12.12