Chidamide in combination with brentuximab vedotin for CD30+ peripheral T-cell lymphoma in patients ineligible for chemotherapy: a prospective phase II study

Abstract Background: The prognosis for patients with peripheral T-cell lymphoma (PTCL) remains extremely poor, posing significant challenges in clinical management. With traditional anthracycline-based chemotherapy regimens such as CHOP (cyclophosphamide + doxorubicin + vincristine + prednisolone), approximately 70% of PTCL patients develop refractory or relapsed disease. Additionally, elderly, unfit, or frail patients often cannot tolerate chemotherapy, resulting in substantial unmet medical needs. Brentuximab vedotin (Bv), an antibody-drug conjugate (ADC) targeting CD30, has demonstrated superior efficacy compared to the traditional CHOP regimen when combined with chemotherapy in CD30-positive PTCL patients. Chidamide (C), the first selective histone deacetylase inhibitor (HDACi) independently developed in China, has shown favorable efficacy and safety profiles in both untreated and relapsed/refractory PTCL patients, whether used as monotherapy or in combination with chemotherapy. Given the mild toxicities of both agents and the proven synergistic effects between epigenetic and targeted therapies, the BvC (brentuximab vedotin plus chidamide) regimen is hypothesized to be effective in CD30-positive PTCL patients who are intolerant to chemotherapy. Aims:This study aims to evaluate the efficacy and safety of BvC regimen in CD30-positive PTCL patients who are unfit for chemotherapy. Methods:This is an ongoing, prospective, multicenter, open-label phase II study (NCT07074457) enrolling CD30-positive PTCL patients ineligible for conventional chemotherapy. Participants will undergo induction therapy with 3 cycles of the BvC regimen: brentuximab vedotin at 1.8 mg/kg on day 1, and chidamide at 20 mg twice weekly for 2 weeks, repeated every 3 weeks. Patients with disease progression (PD) or stable disease (SD) will be discontinued from the study. Those achieving complete remission (CR) or partial remission (PR) will receive 3 or 6 additional cycles of BvC consolidation therapy, respectively. Following consolidation, responding patients (CR/PR) will receive chidamide maintenance therapy (20 mg twice weekly for 2 weeks every 3 weeks) for at least 2 years. The primary endpoint is the complete response rate (CRR) after 3 cycles of BvC. Secondary endpoints include the objective response rate (ORR) after 3 cycles of BvC, 2-year overall survival (OS), 2-year progression-free survival (PFS), and safety profiles in all participants. Results: As of August 1, 2025, a total of 8 patients had been enrolled, comprising 6 males and 2 females, with a median age of 77 years (range: 74-86 years). The baseline characteristics of the enrolled patients were as follows: All (100%) patients had advanced-stage disease with an Eastern Cooperative Oncology Group (ECOG) performance status score of ≥2. Seven patients (87.5%) had elevated lactate dehydrogenase (LDH) levels, and four (50%) presented with extranodal involvement. All patients were classified as high-risk, including five (62.5%) with an International Prognostic Index (IPI) score of 4 and three (37.5%) with an IPI score of 5. Four patients completed at least 3 cycles of BvC therapy, among whom 3 achieved a response: 1 with complete response (CR) and 2 with partial response (PR). This yielded a complete response rate (CRR) of 25% and an overall response rate (ORR) of 75.0%. Adverse events (AEs) were reported in 6 patients (75%), with no cases of grade ≥3 AEs observed. The most common AEs included anemia (62.5%), thrombocytopenia (50%), nausea (37.5%), neutropenia (25%), elevated alanine aminotransferase/aspartate aminotransferase (25%) and elevated creatinine (12.5%). All toxicities were transient and reversible. Conclusions: This preliminary study demonstrates the favorable efficacy and significantly lower hematological toxicities of the BvC regimen in CD30-positive PTCL patients, offering a promising therapeutic option for this challenging population. Further updated clinical data will be shared as the study progresses.