The Efficacy and Safty of Chidamide and Azacitidine Combined with Chemotherapy As a First-Line Treatment in T Follicular Helper Lymphomas: A Comprehensive Retrospective Study

Background: According to most guidelines the standard first-line treatment for peripheral T cell lymphoma(PTCL) remains anthracycline-based chemotherapy and clinical trials. However, evidences have emerged that epigenetic drugs may benefit for T Follicular Helper Cell (TFH) lymphomas (angioimmunoblastic T-cell lymphoma (AITL), PTCL-TfH and Follicular T cell lymphoma) more than other PTCL subtypes. Additionally, the synergistic effects of histone deacetylase inhibitors and DNA methyltransferase inhibitors in PTCL have been demonstrated. In this study we retrospectively analyzed the effectiveness of Chidamide, an oral histone deacetylase inhibitor, and azacitidine(AC) in combination with chemotherapy as first-line treatment in PTCL, focusing primarily on patients with TFH lymphoma.

Methods：We retrospectively analyzed 29 newly diagnosed PTCL patients (mainly AITL and TFH) treated at Hunan Cancer Hospital from July 2021 to July 2024 who received Chidamide and Azacitidine in combination with chemotherapy during their first-line treatment. Chidamide was orally administered 20mg biw every 2 of 3 weeks, azacitidine was administered subcutaneously 100mg on day 1-5 or day 1-7 each 3weeks, both for 6 cycles. Maintanence therapy with Chidamide was recommended. Demographics, response and survival outcomes were collected and analyzed.

Results：

A total of 29 patients were analyzed in this study. The median age of enrolled patients was 56 (34 to 67), 15 females and 14 males. Except for 2 patients diagnosed with PTCL-NOS, the others were diagnosed with AITL or TFH lymphoma. The percentage of stage I, II, III, IV were 0%, 17.2%, 24.1% and 58,7% respectively. Among these 29 patients, 24 patients have completed their AC-based treatment and 5 patients are still undergoing treatment. 25 patients received Chidamide and azacitidine from the first cycle of treatment while 4 patients added Chidamide and azacitined after 2-4 cycles of chemotherapy. The most commonly combined chemotherapy regimen was CHOP (cyclophosphamide, doxorubicin, vincristine and prednisone) (26 patients) followed by mitoxantrone liposomes (3 patients), other chemotheraputic agents included gemcitabine, oxaliplatin and doxorubicin hydrochloride liposome. 17 patients received Chidamide as maintanence therapy while 2 patients underwent auto-ASCT as consolidation therapy. The overall response rate(ORR) was 96.6%, and the complete response rate(CRR) was 69.0%. With a median follow-up of 17 months, the median progression-free survival (PFS) and overall survival (OS) were not reached. Excluding 5 patients who did not complete their first-line treatment, and 4 patients with less than 1 year of folloed-up and without disease progression, the 1-year PFS for the left 20 patients was 75%, and 1-year OS was 90%

There were 3 patients died of disease progression, among which 1 patient was diagnosed with PTCL-NOS and 1 patient discontinued therapy after two cycles for economic reason. The most common adverse effects of this regimen were leukopenia(93.1%), neutrocytopenia(82.8%) and thrombocytopenia(44.8%). Grade 3-4 adverse effects included leukopenia(55.2%), neutrocytopenia(51.7%) and thrombocytopenia(17.2%) . 1 patient with chronic hepatits B developed grade 4 elevation of alanine aminotransferase(ALT) and aspartate aminotransferase(AST) after 2cycles of AC-CHOP, but recovered and finished the rest treatment afterward. Only one patient discontinued treatment due to persistent myelosuppression.

Conclusion: The combination of Chidamide and Azacitidine with chemotherapy as a first-line treatment for TFH lymphoma patients shows high efficacy and manageable safety. Further validation in a larger, randomized controlled trial is warranted.