In recent years, the field of hematologic oncology has seen numerous encouraging breakthroughs, with Chinese scholars increasingly contributing to research in cell therapy, significantly advancing the development of both the discipline and clinical practice. Hematology Frontier specially invited Dr. Ou Bai from The First Bethune Hospital of Jilin University to discuss the progress in the diagnosis and treatment of peripheral T-cell lymphoma (PTCL) in 2024. Dr. Ou Bai shared the groundbreaking advancements in PTCL treatment this year, provided insights into the innovative explorations at their hospital, and offered a forward-looking perspective on new methods and drugs in PTCL therapy.

Hematology Frontier: PTCL is a rare and complex group of hematologic cancers, consistently presenting significant challenges in clinical diagnosis and treatment. Looking back on 2024, were there any breakthrough advancements in diagnosis? Could you share your team’s valuable experience in the precise diagnosis of PTCL?

Dr. Ou Bai: Firstly, in 2024, significant progress was made in circulating tumor DNA (ctDNA) testing for PTCL. ctDNA, as a tumor-specific molecular marker, plays a crucial role in tumor monitoring, minimal residual disease (MRD) assessment, and efficacy evaluation. Ongoing cutting-edge research in this area continues to deepen. At the 2024 European Hematology Association (EHA) Annual Meeting, a study on the application of ctDNA in newly diagnosed PTCL patients attracted widespread attention. The research team ingeniously used ctDNA testing to determine patient prognosis, assess the effectiveness of prognostic models, and explore the relationship between MRD negativity at the end of treatment and patient prognosis. The study focused on four key genes: TP53, TET2, DNMT3A, and RHOA, demonstrating that precise detection of these genes not only aids in accurately determining MRD negativity but, when combined with specific pathological types, can form highly effective predictive models to forecast patient treatment outcomes. This research highlights the critical role and broad prospects of ctDNA detection in PTCL.

Additionally, at the 2024 American Society of Hematology (ASH) Annual Meeting, the international Peripheral T-cell Lymphoma (PETAL) collaboration group introduced a new clinical prognostic index for relapsed/refractory T-cell lymphoma (PIRT). Compared with the previous International Prognostic Index (IPI) and the T-cell lymphoma prognostic index (PIT), the PIRT model exhibited higher predictive accuracy. Statistical tests confirmed significant differences between the PIRT and other models, offering a new perspective and strategy for diagnosing and treating PTCL, providing a more precise tool for patient prognosis assessment.

In 2024, our team at Jilin University’s First Bethune Hospital conducted extensive research in PTCL. For relapsed/refractory PTCL patients, we implemented a next-generation sequencing (NGS)-based testing strategy and molecular stratification for precise treatment selection. This included targeting cell surface characteristics with monoclonal antibody drugs like vedotin, exploring epigenetic therapies with HDAC inhibitors like vorinostat, and combining hypomethylating agents such as azacitidine. We also explored the potential of emerging drugs targeting signaling pathways, such as PI3K inhibitors, JAK inhibitors, and EZH2 inhibitors. Notably, we focused on clinically accessible drugs like PI3K inhibitor duvelisib and selective JAK2 inhibitor fedratinib, conducting exploratory studies on their combined use to provide more diversified and effective treatment options.

At the 2024 ASH Annual Meeting, our team presented a poster on PTCL, evaluating the efficacy and safety of vedotin combined with chemotherapy and vorinostat maintenance therapy in CD30-positive PTCL patients. Results showed an overall response rate (ORR) of 87.9% and a complete response (CR) rate of 75.8% in the frontline treatment group, while the relapse/refractory group had an ORR of 37.5% and a CR rate of 12.5%. The 2-year progression-free survival (PFS) rate and overall survival (OS) rate for the frontline treatment group were 66.7% and 76.9%, respectively. These results demonstrate promising efficacy for vedotin combined with chemotherapy and vorinostat maintenance therapy in treating PTCL, with long-term follow-up data expected to further validate the treatment’s effectiveness and safety.

Hematology Frontier: In 2024, many new treatment strategies and drugs for PTCL were actively explored in clinical trials. Which emerging treatments or drugs do you believe hold the most potential? Which ones should clinicians pay attention to and apply?

Dr. Ou Bai: Significant progress was made in PTCL treatment in the past year, with the most promising developments being new drugs and their combination with traditional therapies. Specifically, novel targeted therapies combined with chemotherapy are addressing a wide range of treatment needs, from initial to relapsed/refractory patients.

Antibody-drug conjugates targeting CD30, such as vedotin, have shown outstanding potential. Additionally, drugs targeting epigenetics, such as HDAC inhibitors romidepsin and vorinostat, have provided new treatment options for PTCL patients. Demethylating agents have also shown efficacy in PTCL research, further energizing the field. A particularly noteworthy advancement is the development of dual EZH1/2 inhibitors, led by Professor Song Yuqin’s team at Peking University Cancer Hospital, with clinical trials expected to complete soon and the drug likely to be launched this year. Early results are promising and could offer a new direction for PTCL treatment.

Immunomodulatory agents like lenalidomide and third-generation IMiDs such as pomalidomide show broad application prospects for PTCL treatment. These agents can be used in combination with kinase inhibitors or basic chemotherapy regimens to achieve better outcomes.

CAR-T cell therapy, targeting specific antigens like CD30, CD70, and CD30/CCR4, has demonstrated exceptional efficacy in relapsed/refractory PTCL treatment, outperforming traditional therapies. The latest progress in CAR-T therapy is certainly worth our attention and continued research. In China, we are at the forefront of CAR-T therapy research, and we hope these studies will soon translate into clinical practice, providing significant and lasting clinical benefits to patients.

Hematology Frontier: Despite the significant progress in PTCL diagnosis and treatment, many challenges and unresolved issues remain. Based on your clinical experience, what challenges and unresolved issues do you believe exist in PTCL diagnosis and treatment? What future research directions should be prioritized?

Dr. Ou Bai: Although the advent of new drugs and combination therapies has significantly improved efficacy, particularly in terms of recent response rates like ORR and CR, long-term survival outcomes such as 5-year or 10-year PFS and OS have not seen significant improvement.

The future challenge remains how to further enhance long-term outcomes for PTCL patients, particularly in improving 5-year OS and PFS rates, achieving deeper remissions, and prolonging survival.

To address this, we need to continue exploring the potential of novel drug combinations and optimize treatment regimens to provide more durable and significant efficacy. We also need to strengthen long-term survival monitoring and assessment to gain a more comprehensive understanding of treatment effects and provide robust data support for future treatment strategies.