The 29th Annual Meeting of the European Association of Blood (EHA) was held in Madrid, the capital of Spain, on June 13~16, 2024, as the largest international conference in the field of hematology in Europe, attracting experts and scholars from all over the world to share and discuss innovative ideas and the latest scientific and clinical research results in hematology every year. At this EHA conference, a number of studies led by Professor Zhang Huilai were selected as Poster, covering the clinical and basic research of lymphoma.
Tumor Lookout-Blood News: Tell us about your team's study on the epidemiological characteristics and prognosis of primary gastrointestinal follicular lymphoma at this EHA meeting (abstract P1136)?
Prof. Zhou Shiyong: Primary gastrointestinal follicular lymphoma (PGI-FL) is a relatively rare disease, but in recent years, with the advancement of medical technology, especially endoscopic technology and equipment, PGI-FL has been increasingly discovered and reported. Compared to intranodal FL (N-FL), PGI-FL has the same immunohistochemical profile and hallmark t(14; 18) Translocation, but PGI-FL mostly presents as local lesions and indolent behavior. In addition, histologic transformation (HT), which is associated with poor prognosis of FL, is extremely rare in PGI-FL, with only a few cases reported to date. Due to the low incidence, most of the current studies on PGI-FL are case reports and retrospective studies, with small cohort sizes and unclear long-term outcomes.
In view of the rarity of PGI-FL and the lack of data on its incidence, clinical features and survival, our team conducted a retrospective study based on the SEER database to analyze epidemiological trends and establish a prognostic nomogram to help accurately assess its prognosis. In the past 40 years, the incidence of PGI-FL has been on the rise, but the prognosis is relatively better than that of FL, and the conversion rate to large B-cell lymphoma (LBCL) is low, medium, and high, which can assist clinicians in identifying high-risk PGI-FL by developing a nomogram to further validate and predict the feasibility of this prediction model, according to the scores generated by the OS nomogram, the PGI-FL patients in the training cohort are stratified into low, intermediate, and high-risk groups, which can assist clinicians in identifying high-risk PGI-FL. Helps to select the best individualized treatment plan.
Tumor Outlook-Blood News: In the POLARIS study (abstract P1141), the application of orelabrutinib combined with lenalidomide and rituximab in the treatment of naïve mantle cell lymphoma was explored.
Prof. Shiyong Zhou: The POLARIS study is a single-arm, multicenter, open-label phase II clinical trial led by Prof. Huilai Zhang's team to explore the efficacy and safety of the combination of orelabrutinib, lenalidomide and rituximab in treatment-naïve mantle cell lymphoma (MCL). MCL is a type of non-Hodgkin lymphoma (NHL) originating from the lymph node mantle, accounting for about 2%~10% of NHL, in the past decade, based on high-dose chemotherapy, immunotherapy and combined application with targeted drugs, the treatment of MCL has made greater progress, but traditional chemotherapy is more toxic, and cannot meet the treatment needs of patients with MCL with high risk of mIPI score, high KI-67 proliferation index, TP53 gene mutation and high histological malignancy. In recent years, the continuous research and development of new drugs has brought new research directions for the treatment of MCL, orelabrutinib is a new type of BTK inhibitor with higher kinase selectivity, which has been approved for the treatment of a variety of lymphomas in China, and clinical research results have shown that orelabrutinib can accurately target BTK and can exert a synergistic anti-tumor effect when combined with CD20 monoclonal antibody. Based on this, this study explored the efficacy and safety of orelabrutinib in combination with lenalidomide and rituximab in treatment-naïve MCL, and a total of 28 treatment-naïve MCL patients were enrolled in the early stage, with an overall response rate (ORR) of 100%, a complete response rate (CR) of 76.2%, and a median duration of response (mDOR) and progression-free survival (mPFS) have not yet been reached. After the end of induction therapy, minimal residual disease (MRD) in bone marrow and peripheral blood was negative. In addition, the safety profile of this triple therapy is good, and the most common adverse effects (AEs) are hematologic toxicity. The triple regimen in this study balances excellent efficacy and good safety profile, allowing more MCL patients to have the possibility of cure in the first line of treatment.
Tumor Lookout-Blood News: In the POLARIS study, the use of NGS to detect peripheral blood ctDNA as an exploratory endpoint indicator has played an important role in the prognosis evaluation of MCL patients, is this test significantly related to the survival of MCL patients?
Prof. Zhou Shiyong: Based on the results of the POLARIS study, we summarized and exploratorily applied NGS to detect the peripheral blood ctDNA level of MCL patients as a highly operable prognostic evaluation and monitoring technology. The results of previous studies showed that higher peripheral blood ctDNA levels in MCL patients were significantly associated with poor prognosis, ctDNA positive had independent poor prognostic predictive value, and peripheral blood ctDNA detection could be conducive to earlier detection of treatment failure and disease progression, and follow-up data showed that the median PFS and overall survival (OS) of mcDNA-positive patients were significantly lower than those of ctDNA-negative patients. The POLARIS study preliminarily verified that there is a significant correlation between peripheral blood ctDNA levels measured by NGS and the survival of MCL patients, but this still needs to be further confirmed by prospective studies with larger sample sizes and longer follow-up periods. In conclusion, the POLARIS study suggests that peripheral blood ctDNA testing may be a promising biomarker in the prognostic evaluation of MCL patients, but more follow-up studies are needed to elucidate it.
Tumor Outlook-Blood News: In another study (abstract P1226), it was shown that CD58 gene mutations regulate the expression of PD-L1 and IDO through the LYN/CD22/SHP1 axis, which in turn affects the anti-tumor effect in diffuse large B-cell lymphoma.
Prof. Shiyong Zhou: This study is another major breakthrough made by our team under the leadership of Prof. Zhang Huilai, through the gene sequencing (NGS) data of our center, the CD58 gene mutation rate of patients with diffuse large B-cell lymphoma (DLBCL) reached 9.1%, and the copy number deletion was about 44.7%, and the CD58 gene mutation and low expression were significantly correlated with the reduction of response rate, progression-free survival and overall survival of R-CHOP regimen. Notably, this study by our team discovered that CD58 gene mutations affect a novel mechanism of DLBCL immune escape, and CD58 gene mutations or down-regulation of expression regulate the expression of PD-L1 and IDO through the LYN/CD22/SHP1 axis, resulting in multiple pathways-mediated immune escape and inducing tumor cells to reduce their sensitivity to CAR-T cell therapy. Therefore, this study highlights the critical role of CD58 gene mutations in DLBCL, which can affect the efficacy and immune escape of anti-tumor therapy through multiple mechanisms, and provides a potential target and therapeutic strategy for improving the treatment outcome and prognosis of patients with DLBCL.
Professor Zhang Huilai
Tianjin Medical University Cancer Hospital
Director of the Department of Lymphoma Medicine
Chief physician
Doctor of Oncology, Doctoral Supervisor, Clinical Level I PI
Member of the Lymphoma Quality Control Expert Committee of the National Cancer Center
He is a member of the 9th Council of the Chinese Anti-Cancer Association, vice chairman of the Lymphoma Professional Committee of the Chinese Anti-Cancer Association, and a member of the Standing Committee of the Lymphoma Expert Committee of the Chinese Society of Clinical Oncology (CSCO). The second batch of high-level talents in the health industry in Tianjin, the first level of talents in the "Clinical Talent Training 123 Climbing Plan" of Tianjin Medical University Hospital, and the excellent graduate tutor team of Tianjin Medical University in 2023.
He has won 1 third prize of the Chinese Medical Science and Technology Award, 1 science popularization award of the Chinese Anti-Cancer Association, 1 second prize and 3 third prizes of Tianjin Science and Technology Progress Award. As the first or corresponding author, he has published more than 90 papers in international professional journals such as Blood, Cancer Research, J Exp Med, JITC, Leukemia, CTM, AJH, BJH, Blood Adv, Int J Cancer, etc., as well as Chinese series of magazines and national core journals. Won the 4th "National Famous Doctor· Excellent Style" award.
Professor Zhou Shiyong
Doctor of Medicine, Deputy Chief Physician
Deputy Chief Physician of the Department of Lymphoma, Tianjin Medical University Cancer Hospital
Member of the Standing Committee of the Tumor Immunotherapy Professional Committee of the Chinese Geriatric Health Care Association
He is a member of the Lymphoma Professional Committee of Tianjin Anti-Cancer Association
Member of the Hematology Branch of Tianjin Medical Doctor Association
Member of the Chemotherapy Committee of Tianjin Anti-Cancer Association
He is a member of the Tianjin Professional Committee for the Treatment of Adverse Reactions in Cancer Treatment
He is a member of the Lymphatic Diseases and Lymphoma Professional Committee of the Chinese Medical Education Association
Member of the Youth Committee of the Cancer Rehabilitation Branch of the Chinese Society of Gerontology and Geriatrics