Peripheral T-cell lymphoma (PTCL) is a heterogeneous disease with poor prognosis. Standard CHOP (cyclophosphamide, doxorubicin, vincristine, and prednisone) chemotherapy is the most widely used regimen for first-line treatment of PTCL. Combining targeted drugs with CHOP holds significant promise for improving patient outcomes.
At this year’s International Conference on Malignant Lymphoma (ICML 2023), Dr.Xu Pengpeng from Ruijin Hospital, School of Medicine, Shanghai Jiao Tong University, China, presented exciting results from the “Targeted Drug Combination with CHOP vs. CHOP as First-Line Treatment for Peripheral T-cell Lymphoma: Preliminary Results of the Phase II GUIDANCE-03 Trial.” Oncology Frontier had the privilege to interview Dr. Xu Pengpeng about this study.
Oncology Frontier: PTCL currently has poor overall efficacy and prognosis. CHOP+X is one of the research directions to improve efficacy. Can you elaborate on the targeted drug X used for treating PTCL?
Dr. Xu Pengpeng: Currently, the overall treatment efficacy for PTCL is unsatisfactory. Based on past experience, using the classic CHOP treatment regimen yields a 5-year overall survival rate of approximately 30%, meaning that the majority of PTCL patients inevitably experience disease progression or relapse within 5 years. To address this, we conducted a clinical study involving CHOP+X, where different targeted drugs were added based on the patient’s specific genetic mutations. The aim was to explore whether precise targeted therapy could enhance the efficacy of PTCL patients on the foundation of the CHOP treatment. In the study, we added idasanutlin (for p53 mutations), azacitidine (for TET2/KMT2D mutations), lenalidomide (for CREBBP/EP300 mutations), and daratumumab (for other mutations apart from the mentioned ones). Alongside these drugs, a series of targeted therapies, such as CD30 monoclonal antibodies like brentuximab vedotin, have also been applied in clinical
practice and have shown good efficacy.
Oncology Frontier: At this ICML conference, your team’s study (abstract 42) compared the efficacy difference between CHOP+X and the standard CHOP regimen in PTCL treatment. Could you provide a detailed interpretation of the study?
Dr. Xu Pengpeng: This study was a pragmatic clinical trial (PCT), focusing on adding different targeted drugs based on the molecular mutations of PTCL patients. By comparing it with the classic CHOP regimen, we aimed to see whether CHOP+X could offer further improvement in complete response rate (CRR) and survival. The study included 96 patients, with 48 in the CHOP+X group and 48 in the CHOP group. The two groups had similar demographics, including age, gender, Ann Arbor stage, physical condition, and prognostic risk. The median age of patients was 63 years, and the majority were elderly patients in advanced disease stages, categorized as high risk by the International Prognostic Index (IPI).
The results showed that compared to the CHOP group, the CHOP+X group had an approximately 30% increase in CRR. Although the median follow-up time was just over one year, a favorable trend in progression-free survival (PFS) was observed, while no significant differences were seen in overall survival (OS) between the two groups. Regarding adverse events, the CHOP+X group had a slightly increased incidence of hematologic adverse events, but there was no significant rise, including non-hematologic adverse events related to infections of grades 3-4. Therefore, we believe that the approach of CHOP+X, tailoring treatment based on the PTCL patient’s subtype, is worth further exploration.
Oncology Frontier: Discuss the current treatment status for relapsed/refractory PTCL. Additionally, what progress has been made with drugs like lenalidomide, brentuximab vedotin, etc., in its treatment?
Dr. Xu Pengpeng: For relapsed/refractory PTCL patients, there are now more treatment options than before due to the availability of several targeted therapies. Lenalidomide and brentuximab vedotin are representative choices. However, based on our center’s experience, although these two drugs are very promising and highly effective treatment options, it might be necessary to further combine them with chemotherapy or other targeted therapies to achieve a higher remission rate. This, in turn, could allow patients to proceed to additional consolidation treatments such as autologous hematopoietic stem cell transplantation. We hope to see more targeted therapies in the future that can synergize with existing treatment approaches, providing more PTCL
patients with the hope of cure.
TAG: ICML 2023, Interview, Voice of China，Hematological Malignancy, PTCL
