The Short-Term Efficacy and Safety of Brentuximab Vedotin Chemotherapy Combined with Chidamide in the Treatment of CD30-Positive Peripheral T-Cell Lymphoma

Background:

CD30-expressing peripheral T-cell lymphoma (PTCL) may have a particularly poor prognosis. Post-treatment recurrence rates in PTCL are alarmingly high, reaching 75%, with short median progression-free survival (PFS) and overall survival (OS). Consequently, numerous studies now focus on optimizing and enhancing anthracycline-based regimens, particularly through the significant ECHELON-2 trial. This trial compared brentuximab vedotin(BV) combined with CHP (A+CHP) against CHOP, showing a 5-year PFS of 51% and a 5-year OS of 70%. However, these results predominantly involved patients with ALCL. Other subtypes are limited. Therefore, novel first-line treatment strategies and post-remission consolidation/maintenance regimens for PTCL are urgently required. Chidamide is a novel histone deacetylase inhibitor. Pre-clinical mouse models have shown that BV and chidamide act synergistically, increasing the efficacy of treatment of xenograft tumors derived from HH lymphoma cells. However, there are few real-world reports on the efficacy and safety of the combination of BV and chidamide in treating patients with PTCL.

Aims:

This study aimed to evaluate the safety and efficacy of the combined use of BV and chidamide in the treatment of CD30-positive PTCL.

Methods:

Patients was received BV combined with chemotherapy (first line or the second or above-line regimen) for 4 cycles, then BV combined with adjust dose of chemotherapy for 2 cycles, followed by chidamide 20mg two times per week as maintenance treatment. 41 patients between February 2021 and July 2024 in our center with histologically confirmed PTCL (CD30 was positive) were enrolled, with a median follow-up of 23.2 months (range, 5-51 months). We evaluate the efficacy and safety of this strategy.

Results:

A total of 41 patients were enrolled. Of these, 23 were male（56.0%) and 18 were female（43.9%), with a median age of 58 (35-79) years. The clinical characteristics included ALCL 7 (17%), AITL 24 (58.5), PTCL（NOS）4 (9.8%), and NK/T 6 (14.6%). Thirty-seven patients (90.2%) had advanced-stage PTCL, 31 (75.6%) were classified as high risk, 90.2% had extra-nodal involvement, and 70.7% had EB virus infection. Thirty-three patients (80.5%) received BV combined with chidamide therapy as the first-line treatment, while 8 (19.5%) were classified as relapsed/refractory and received the treatment as second or above-line therapy.

The first-line treatment group showed an ORR of 87.9% with a CRR of 75.8%. Patients receiving second or above-line treatment had an ORR of 37.5% and CRR of 12.5%. Three patients died from disease progression, one patient died from pneumonia resulting from COVID-19, and one patient died following myocardial infarction. Further analysis revealed that the two-year PFS and OS values of the first-line treatment group were significantly better (PFS 66.7% , OS 76.9%).

No differences in ORR were observed between the different patient subtypes in the first-line therapy group（100% vs. 85.6% vs. 80.0% vs. 100%, p=0.373). One patient in the ATIL subgroup achieved PR during the first four cycles of BV-chemotherapy, changing to CR after combined treatment with chidamide.

Of the five patients who were infected with EB virus infection, the viral load decreased to normal during the first three cycles, while in two patients with lymphoma progression and EB infection, the viral load remained high. No patients showed hemophagocytic syndrome.

In terms of treatment-related side effects, the incidence of any adverse event was 28 (87.5%) , of whom 9 patients (21.9%) had grade III or above disease. In terms of these side effects, 15.9% of patients had neutropenia, 9.4% had anemia, 18.8% had thrombocytopenia, and 3.1% had pneumonia. Two patients required blood transfusions. Only 1 patient delayed treatment because of the side effects.

Conclusion:

In conclusion, Brentuximab vedotin combined with chemotherapy and chidamide as a maintenance treatment is both safe and effective for the treatment of PTCL. Similar results were found in different patient subtypes. Patients who received this treatment as first-line therapy had better ORR, CRR, and PFS. The adverse effects were relatively benign and controllable. Nevertheless, further follow-up is required to determine the long-term efficacy and safety of this treatment strategy.