Azacitidine and Chidamide Added to CHOP Improves OS but Not ORR in PTCL

In a multicenter phase 3 trial, the addition of the epigenetic agents azacitidine and chidamide to CHOP chemotherapy (AC-CHOP) in previously untreated peripheral T-cell lymphoma (PTCL) did not significantly improve overall response rate (ORR) or progression-free survival (PFS), but a significant overall survival (OS) benefit was observed. The study enrolled 128 patients from 9 centers in China, who were assigned to receive AC-CHOP (n=84) or CHOP alone (n=44). Azacitidine was administered at 200 mg on days 1-2 and 100 mg on day 3, with chidamide 20 mg twice weekly. The AC-CHOP arm achieved an ORR of 60.7% and complete response (CR) rate of 47.6%, compared to 54.6% and 36.4% in the CHOP arm, although these differences were not statistically significant. Median PFS was 10.2 months versus 8.4 months (P=0.093). Median OS was significantly longer at 46.2 months versus 24.1 months (P=0.023). The authors noted, however, that the OS improvement should be interpreted cautiously due to imbalances in post-protocol treatments between the arms. Safety profiles were comparable, with hematologic toxicity and infection as the most common adverse events. Genomic profiling revealed that DNMT3A mutations were associated with lower response rates, while IDH2 and TP53 mutations were linked to inferior survival outcomes. The researchers concluded that integration of molecular profiling may improve risk stratification and inform future biomarker-driven strategies in PTCL.