Mitoxantrone Hydrochloride Liposome (Lipo-MIT) Combined with Azacitidine and Chidamide Can be an Effective Chemotherapy Regimen for Patients with Angioimmunoblastic T-Cell Lymphoma (AITL)

Introduction: 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. Mitoxantrone hydrochloride liposome (PLM60) is a nano-drug that has been approved as one of the treatment options for relapsed/refractory R/R AITL (ORR 64%) in previous. 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 2024, 5 pts with newly-diagnosed and 6 pts with relapsed/refractory AITL (6 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 6 pts with R/R AITL, 3 (50%) pts had received 1st-line chemotherapy, 1 (35.7%) patients had received 2nd-line chemotherapy, 1 (7.1%) patient had received 5th-line chemotherapy. The median age was 66 years (range 39-74) and 7 (63.6%) patients were male. All patients had stage III/IV disease, and 8 (72.7%) had IPI score ≥3. All patients completed at least one cycle of the MAC regimen treatment, and 8 pts were evaluable (3 pts were ND AITL and 5 pts were R/R AITL). Among 3 ND pts, the best ORR rate was 100% (3/3) and CRR was 66.7% (2/3). For the 5 R/R pts, the best ORR rate was 100% (5/5) and CRR was 60% (3/5). 4 pts achieved CR within 2 cycles of treatment. Other efficacy indicators such as PFS (progression-free survival) and OS (overall survival) will be reported after long-term follow-up. Treatment related adverse events (TRAEs) occurred 5 (45.5%) pts. The most prevalent grade 3 or higher treatment-related adverse events included neutropenia (n=4, 36.4%), lymphopenia (n=4, 36.4%), and Infection (n=2, 18.2%). All pts were successfully recoverd from these TRAEs through the implementation of clinical supportive care. There were no treatment-related deaths, adverse cardiac eventsadverse cardiac events, pulmonary fibrosis and interstitial pneumonia.

Conclusions: 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.

No relevant conflicts of interest to declare.