Efficacy and Safety of Mitoxantrone Hydrochloride Liposome Injection Combined with Carmustine, Etoposide and Cytarabine As Conditioning Regimen for Autologous Hematopoietic Stem Cell Transplantation in Non-Hodgkin Lymphoma Patients
Authors: Wang Xiaoning , Wang Yuqi , Ren Juan , Zhu Huachao , He Pengcheng 
Published: December 2024

Background: High-dose chemotherapy followed by autologous hematopoietic stem cell transplantation (ASCT) is the standard of care for patients with relapsed/refractory non-Hodgkin lymphoma (NHL). BEAM (carmustine, cytarabine, etoposide and melphalan) and BEAC (carmustine, cytarabine, etoposide and cyclophosphamide) are the most widely used conditioning regimens for NHL, which is limited by dose-limiting toxicities. Therefore, it is necessary to explore effective conditioning regimens with low toxicity. Mitoxantrone hydrochloride liposome (Lipo-MIT) is a pegylated liposomal mitoxantrone formulation with promising efficacy and an acceptable safety profile in multiple subtypes of NHL. Our study aims to evaluate the efficacy and safety of mitoxantrone liposome (PLM) combined with camustine, etoposide, and cytarabine (BEA-PLM) as a conditioning regimen for ASCT in patients with NHL (NCT05681403).

Methods: This isa prospective, single-arm, exploratory study for NHL patients undergoing ASCT following conditioning with BEA-PLM regimen, consisting of PLM 24 mg/m2 on day -7, camustine 300 mg/m2 on day -6, cytarabine 200 mg/m2 (q12h) on day -5~-2 and etoposide 200 mg/m2 on day-5~-2. The primary endpoint was the 1-year cumulative incidence of relapse. Secondary endpoints included 1-year progression-free survival (PFS), 1-year overall survival (OS), times to neutrophil engraftment and platelet engraftment, and non-hematological toxicity. The historic cohort of BEAM/BEAC used for the comparative analysis was collected from an electronic health record between January 2018 and February 2022.

Results: From March 2022 to December 2023, a total of 38 patients with NHL who conditioning with BEA-PLM regimen were enrolled in our center, all of whom successfully achieved hematopoietic reconstruction, while 49 patients was collected in the BEAM/BEAC group. Compare with the historical cohort, no significant differences were observed in the 1-year cumulative incidence of relapse (12.6% vs. 24.9%), 1-year PFS (87.4% vs. 75.1%), and 1-year OS (100% vs. 83.7%) (all p &gt; 0.05), but there was a trend of decreased incidence of relapse and improved survival in the BEA-PLM group. Besides, the median time to platelet engraftment did not show a significant difference between the BEA-PLM and BEAM/BEAC groups (11.0 vs. 10.0 days, p = 0.093), whereas there was a significant delay in neutrophil engraftment in the modified BEAM group (10.5 vs. 9.0 days, p &lt; 0.001). Oral mucositis (18.4% vs. 14.3%), nausea (7.9% vs. 8.2%), diarrhea (5.3% vs. 8.2%) and vomiting (2.6% vs. 0.0%) were the most common grade 3-4 non-hematologic toxicities in both groups. No treatment-related death was reported.

Conclusions: The BEA-PLM conditioning regimen demonstrated comparable efficacy and safety to the BEAM/BEAC regimen in treating patients with NHL.

Keywords: autologous hematopoietic stem cell transplantation; BEAM/BEAC; conditioning regimen; mitoxantrone hydrochloride liposome; non-Hodgkin lymphoma