Real-World Efficacy of 5-Azacytidine as Salvage Chemotherapy for Angioimmunoblastic T-cell Lymphoma

Background: Based on specific epigenetic mutation in AITL such as TET2, DNMT3A, IDH2, and RHOA, hypomethylating agents are emerging as a promising treatment option for AITL. Method: The efficacy and safety of 5-azacytidine as salvage chemotherapy were retrospectively analyzed in 15 patients with RR-AITL from 2019 to 2022. Results: During the median 6.0 months of follow-up, the overall response rate (ORR) was 40% (n = 6/15) with 2 CRs and 4 PRs. The patients who previously had received ≤2 prior chemotherapies showed higher ORR than subjects with >2 prior chemotherapies (80% vs. 20%). The 10 patients who received 5-azacitidine at the late chemotherapy lines (>2 prior chemotherapy lines) usually received less dose 5-azacitidine. And these patients discontinued treatment due to disease progression (n = 6/10, 60%) or neutropenic fever (n = 4/10, 40%). The patients who received a full dose (75 mg/m² for 7 days) of 5-azacitidine seemed to show better ORR than subjects (100 mg for 7 days) who did not receive an optimal dose (60.0% vs. 30.0%). The median progression-free survival (PFS) was 1.6 months, and the patients who previously had undergone ≤2 chemotherapies had better PFS compared with subjects who previously received >2 chemotherapies (P-value = .04). Conclusion: 5-azacitidine shows reasonable efficacy and manageable toxicities for patients with RR-AITL, especially those who previously received ≤2 chemotherapy lines.