Mitoxantrone hydrochloride liposome (Lipo-MIT) combined with azacitidine and  Chidamide can be an effective chemotherapy regimen for patients with angioimmunoblastic T-cell lymphoma (AITL)

Abstract Background: Angioimmunoblastic T-cell lymphoma (AITL) originates from follicular helper T-cell (THF), is the second most common subtype of peripheral T-cell lymphoma (PTCL), accounting for 19% of all T-cell lymphoma cases, which are characterized by a high degree of malignancy, rapid progression and poor prognosis. Currently, cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP) is the most common first-line chemotherapy regimen. But previous studies have reported the 5-year PFS of AITL is 13%-23%, and overall survival (OS) of <40%, effective treatment is urgently needed in the clinic. With the popularization of high-throughput sequencing, AITL epigenetic (DNA methylation modification, histone modification) mutations are prevalent, providing powerful targets for targeted therapy. Previous studies have showed 64% ORR for mitoxantrone hydrochloride liposome (Lipo-MIT) monotherapy in AITL. This study aimed to evaluate the efficacy and safety of mitoxantrone hydrochloride liposome (Lipo-MIT) in combination with azacitidine and chidamide (MAC) in newly diagnosed (ND) and relapsed/refractory AITL (ChiCTR2300075418). Methods: Patients with newly diagnosed and relapsed/refractory AITL were treated with up to 6 cycles of the MAC regimen, administered every 4 weeks. Lipo-MIT was intravenously administered on Day 1 at a dose of 15-20 mg/m2 in combination with azacitidine (75 mg/day, Days 1-7) and chidamide (20 mg, twice a week). Imaging examinations were performed every two cycles to evaluate therapeutic efficacy. The primary endpoint of the study was the overall response rate (ORR). The secondary endpoints included progression-free survival (PFS), complete response rate (CRR), overall survival (OS), and adverse events (AEs). Results: Between Nov 2022 and June 2025, 8 pts with newly-diagnosed and 9 pts with relapsed/refractory AITL (8 pts were refractory) were enrolled. The median dose of Lipo-MIT in the regimen was 17.3mg/m2 (range, 11.7-19mg/m2). Among the 9 pts with R/R AITL, 5 (55.6%) pts had received 1st-line chemotherapy, 4 (33.3%) patients had received more than 2nd-line chemotherapy, 1 (11.1%) patient had received 5th-line chemotherapy. The median age was 67 years (range 39-74) and 9 (52.3%) patients were male. All patients had stage III/IV disease, and 13 (76.5%) had IPI score ≥3. All patients completed at least one cycle of the MAC regimen treatment, and 14 pts were evaluable (7 pts were ND AITL and 7 pts were R/R AITL). Among 7 ND pts, the best ORR rate was 100% (7/7) and CRR was 100% (7/7). For the 7 R/R pts, the best ORR rate was 100% (7/7) and CRR was 71.4% (5/7). 10 pts achieved CR within 2 cycles of treatment. Median follow-up of 13 months (3-33) , one year PFS was 100% in ND pts and 85.7% in the R/R pts. Treatment related adverse events (TRAEs) occurred 6 (35.3%) pts. The most prevalent grade 3 or higher treatment-related adverse events included neutropenia (n=6, 35.3%), lymphopenia (n=4, 23.5%), and Infection (n=3, 17.6%). Patients all successfully recoverd from these TRAEs through the implementation of clinical supportive care. There were no treatment-related deaths and adverse cardiac events. Conclusion This study showed that the Lipo-MIT combined with azacitidine and chidamide (MAC) regimen is associated with high response rate and manageable toxicity in patients with newly diagnosed and relapsed/refractory AITL. It deserves further large-sample studies to confirm efficacy and safety.