Azacytidine combined with CHOP regimen for the treatment of newly diagnosed angioimmunoblastic T-cell lymphoma

Abstract

Abstract Introduction Angioimmunoblastic T-cell lymphoma (AITL) represents an aggressive malignancy derived from follicular helper T cells. Characteristic genetic mutations, including alterations in TET2, DNMT3A, IDH2, and the RHOA G17V variant, underpin the pathogenesis of this lymphoma subtype. Comprehensive investigations underscore the transformative potential of epigenetic-targeting agents in exerting pronounced anti-lymphoma activity.Methods This prospective study evaluates the therapeutic potential and safety profile of azacitidine combined with CHOP chemotherapy (ACHOP) in previously untreated AITL patients. Inclusion criteria encompassed patients aged 18–75 years with untreated AITL and an Eastern Cooperative Oncology Group (ECOG) performance status of 0–3. The therapeutic regimen administered azacitidine (75 mg/m², days 1–5) alongside CHOP chemotherapy every 21 days for four cycles. Patients achieving complete remission (CR) proceeded to an additional four ACHOP cycles, followed by recommendations for autologous stem cell transplantation (ASCT) in eligible patients aged under 65 years. Maintenance therapy with the histone deacetylase (HDAC) inhibitor chidamide was advised for two years for all participants. The study's primary endpoint assessed the CR rate, while secondary endpoints included overall response rate (ORR), progression-free survival (PFS), overall survival (OS), and safety evaluation.Results Fifty-two treatment-naïve AITL patients were sequentially enrolled, with a median age of 63 years (range: 41–75 years). Advanced disease was prevalent, with 96.2% (50 patients) classified as stage III or IV per the Ann Arbor staging system. Constitutional symptoms such as high-grade fever were present in 13 patients at baseline. Extranodal involvement was noted in 75% (39 patients), and 80.8% (42 patients) presented with an International Prognostic Index (IPI) score ≥2. Elevated Epstein-Barr virus (EBV) DNA levels (>500 copies/mL) were detected in 36 participants. All 52 participants received at least one cycle of azacitidine plus CHOP as of July 11, 2025. Of 48 evaluable patients, an ORR of 87.7% (43/49) was observed, comprising a CR rate of 73.4% (36/49) and a partial remission (PR) rate of 14.3% (7/49). Eleven patients experienced CR relapse, with seven relapsing within 12 months. The median follow-up period was 22 months. Median PFS reached 27 months, whereas median OS had not been reached at analysis time. Two-year PFS and OS rates stood at 63.2% and 83.7%, respectively. The ACHOP regimen displayed an acceptable safety profile. Common adverse events included leukopenia, anemia, and thrombocytopenia. Grade 3 or higher toxicities predominantly involved neutropenia, thrombocytopenia, infections, and pneumonia. No treatment-related deaths occurred.Conclusions The combination of azacitidine and CHOP presents a compelling therapeutic option with robust efficacy and manageable toxicity as a first-line treatment for AITL.