Editor’s Note: From June 13-17, 2023, the biennial International Conference on Malignant Lymphoma (ICML), the largest global event in the field, took place in the picturesque town of Lugano, Switzerland. Gathering top lymphoma experts worldwide, the conference featured cutting-edge research in lymphoma fundamentals, clinical practices, translational medicine, and new drug development, contributing to the advancement of global lymphoma diagnosis and treatment. Particularly noteworthy was the “UCLI-ICML Joint Session” held on the afternoon of June 16 from 14:30 to 17:30. Co-hosted by Dr.Franco Cavalli, President of ICML, and Dr.Ma Jun from the Harbin Institute of Hematology and Oncology, China, the session included presentations by young scholars from China. They shared insights on building lymphoma databases, new drug development, and, notably, first-line treatment experiences using domestically developed PD-1 drugs for high-risk IIB stage and advanced classical Hodgkin lymphoma patients. Oncology Frontier had the privilege of inviting three distinguished young Chinese lymphoma scholars who delivered insightful presentations during this joint session: Dr.Liu Weiping from Peking University Cancer Hospital, Dr. Li Zhiming from Sun Yat-sen University Cancer Center, and Dr.Zhou Keshu from Henan Cancer Hospital. They graciously shared their research achievements with fellow professionals.
Dr. Liu Weiping: Establishment of the National Lymphoma Standard Database in China and Big Data Analysis
In 2021, under the leadership of the National Health Commission, we initiated the construction of the “National Health Commission Lymphoma Standard Database.” As of March 2023, the database has incorporated data from 16,000 lymphoma patients. At this ICML conference, we presented preliminary analyses based on representative data from 10,000 patients in this database. The analysis primarily reflects the epidemiological characteristics of lymphoma patients in China and the current treatment landscape, uncovering some of the challenges we currently face.
Our research indicates that the median age of all patients is 54, with approximately one-third of them being elderly individuals aged 60 and above. This highlights the aging trend among lymphoma patients in China. Additionally, we analyzed the comorbidities of the patients since, in clinical practice, comorbidities often influence treatment decisions despite standard treatment recommendations. As anticipated, 18% of all patients had a history of hypertension, 12% had a history of diabetes, and one-third of the patients were either overweight or obese. These conditions inevitably impact the patients’ adherence to standard treatment.
We initiated data entry into the database in May 2022, and as of now, it has been exactly one year. We expect that over 200 medical centers will participate in the construction of this database, and the lymphoma patient data will surpass 100,000 cases. This will become a valuable clinical sample repository, enabling us to conduct more in-depth epidemiological studies, real-world research, and prospective studies based on this extensive lymphoma database. The goal is to explore new targets for lymphoma treatment and drive new drug development. All these data will not only guide standardized diagnosis and treatment across regions but also provide robust support for the revision of China’s lymphoma diagnosis and treatment guidelines, holding significant evidence-based medical significance. Moreover, based on this data, we can provide essential data support for China’s lymphoma prevention and control policies.
Dr. Li Zhiming: First-Line Treatment of Advanced Classical Hodgkin Lymphoma with Tislelizumab Monotherapy or in Combination with AVD, A Wise Choice?
Hodgkin lymphoma (HL) is a curable disease, with current treatment primarily involving combination chemotherapy. However, for advanced or IIB stage HL patients with at least one high-risk factor, the efficacy of the conventional ABVD regimen alone is not always satisfactory. Therefore, some scholars internationally propose the use of higher-dose chemotherapy regimens. In recent years, with the gradual rise of immunotherapy in Hodgkin lymphoma, PD-1 antibody drugs have transitioned from third-line or later treatments to second-line treatments, even surpassing brentuximab vedotin (BV). At this year’s American Society of Clinical Oncology (ASCO) Annual Meeting, the notable SWOG S1826 Phase III clinical randomized controlled trial results were revealed (ASCO 2023 Abstract LBA4). The study compared the effectiveness and safety of nivolumab (N) + AVD with brentuximab vedotin (BV) + AVD in treating advanced classical Hodgkin lymphoma (cHL) and demonstrated that N+AVD significantly improved patients’ progression-free survival (PFS) compared to BV+AVD. Hence, we can observe that the combination of immunotherapy and chemotherapy has surpassed targeted therapy combined with chemotherapy.
Previous studies have shown that tislelizumab monotherapy has a high objective response rate (ORR) and complete response (CR) rate in relapsed and refractory cHL patients. Additionally, while chemotherapy has a potent anti-tumor effect in HL patients, the adverse reactions and long-term adverse effects associated with chemotherapy are enduring concerns for patients. Therefore, at this ICML conference, we reported the efficacy and safety of tislelizumab monotherapy, either alone or in combination with AVD, in the first-line treatment of cHL.
Our study included untreated advanced cHL patients. All patients initially received two cycles of tislelizumab monotherapy, followed by PET-CT evaluation (PET-2). Based on PET-2 results, patients achieving CR continued to receive four cycles of tislelizumab monotherapy, while those with partial response (PR) received a combination of four cycles of tislelizumab + AVD. Patients with progressive disease (PD)/stable disease (SD) exited the study. After six treatment cycles, patients maintaining PR, as assessed by PET-CT (PET-3), could receive an additional two cycles of tislelizumab + AVD combination therapy. The primary endpoint was the CR rate at PET-2, and secondary endpoints included ORR, PFS, overall survival (OS), and safety.
As of February 27, 2023, a total of 29 patients participated in the study, with one patient excluded due to peripheral T-cell lymphoma diagnosis. The median age was 34 years (21-68 years), with 10.7% in IIB stage, 25.0% in III stage, and 64.3% in IV stage. All 28 eligible patients received at least two cycles of tislelizumab monotherapy and PET-2 efficacy assessment. The efficacy and overall survival rate curves are shown in Figure 1. After PET-2, the CR rate was 28.6% (8/28), and the overall response rate (ORR) was 96.4% (27/28), with one patient (3.6%) experiencing PD. By PET-3, 21 patients had completed all treatments, while the remaining 7 were still undergoing treatment. During treatment, 19 patients (90.5%, 19/21) achieved CR, 1 patient (4.8%) achieved PR, and 1 had PD, resulting in a 95.2% ORR. During follow-up, among the 8 CR patients at PET-2, 6 maintained CR after six cycles of tislelizumab monotherapy, avoiding the need for chemotherapy. The study demonstrated good tolerance, with no treatment-related serious adverse events (SAEs) or deaths reported. Immunotherapy-related adverse events were mainly grades 1/2, and grade 3/4 hematologic toxicities occurred primarily during combination therapy.
Figure 1. Efficacy and Overall Survival Rate Curves Based on PET-2 Assessment
The study results indicate that tislelizumab demonstrates excellent efficacy and safety. In some advanced classical Hodgkin lymphoma (cHL) patients, chemotherapy regimens can even be reduced or omitted. Therefore, the tislelizumab in combination with AVD regimen appears to be a promising first-line treatment option for cHL.
Dr. Zhou Keshu: The Global Trend of New Drug Development for Lymphoma in China
In 2018, China contributed 7.8% of innovative drug applications and 11.6% of newly approved drugs globally, establishing itself as the largest pharmaceutical research and development hub in Asia. From statistical data, the field of oncology, especially lymphoma, is a major battleground for new drug development. Despite substantial progress in the treatment of B-cell lymphoma (BCL), there are still unmet needs for patients who cannot be cured.
Zanubrutinib, developed independently by BeiGene, is a BTK inhibitor that received accelerated approval from the U.S. FDA in November 2019 for the treatment of mantle cell lymphoma (MCL) patients who had received at least one prior therapy. It is considered a critical breakthrough for Chinese innovative drugs going global, marking a significant leap from 0 to 1. Zanubrutinib is hailed as the best BTK inhibitor in its class, exhibiting greater kinase selectivity and less off-target toxicity compared to other BTK inhibitors.
In two Phase III head-to-head trials against ibrutinib, zanubrutinib demonstrated excellent overall response rates (ORR) and progression-free survival (PFS) in relapsed/refractory CLL/SLL patients and deeper and more persistent responses in Waldenström macroglobulinemia (WM) patients. Notably, the ROSEWOOD trial showed that in relapsed/refractory follicular lymphoma (FL) patients, zanubrutinib + obinutuzumab significantly improved patient PFS compared to obinutuzumab monotherapy. Furthermore, a Phase III clinical trial is underway, comparing zanubrutinib + rituximab with bendamustine + rituximab in untreated and non-transplant eligible MCL patients. As of now, zanubrutinib has been approved in more than 60 countries for the treatment of CLL/SLL, WM, MCL, and MZL, and efforts are ongoing to seek approvals for broader indications globally.
APG-2575, developed by Ascentage Pharma, is a novel oral Bcl-2 selective small molecule inhibitor. A global multicenter Phase II clinical study showed that APG-2575, either as monotherapy or in combination with acalabrutinib and rituximab, demonstrated excellent early efficacy and manageable safety in treatment-naive, relapsed, or refractory chronic lymphocytic leukemia/small lymphocytic lymphoma (R/R CLL/SLL) patients. Additionally, BGB-11417, another domestically developed Bcl-2 inhibitor with improved structural modifications and higher activity and selectivity against Bcl-2 protein, has shown promising efficacy and safety data in clinical studies for treating R/R CLL/SLL patients and is currently undergoing global clinical research.
In summary, the emergence of these innovative drugs provides new possibilities for the clinical treatment of BCL. Beyond BCL, a Phase I/II clinical study has demonstrated that the selective JAK1 inhibitor golidocitinib has significant anti-tumor activity and manageable safety in relapsed/refractory peripheral T-cell lymphoma (PTCL) patients. Moreover, there are many other innovative drugs in clinical research in China, with the potential to go global in the future.
In conclusion, China has evolved into one of the largest global pharmaceutical research and development markets. From participation to leadership, from “best in class” to “first in class,” China possesses immense potential for innovative cancer drug development.
TAG: ICML 2023, UCLI-ICML Joint Session,Commentary, Voice of China，Hematological Malignancy, Lymphoma
