Mitoxantrone Hydrochloride Liposome (Lipo-MIT) Combined with R-GDP Regimen in Relapsed/Refractory Diffuse Large B-Cell Lymphoma: A Multicenter, Single-Arm Study
Authors: Ma Li , Zhao Jin , Wang Jingrong , Zheng Meijing , Wen Xiaolian , Lang Junyuan , Yang Bin , Su Liping 
Published: December 2024

Background: DLBCL is an aggressivenon-Hodgkin lymphoma(NHL) that is commonly can be curable with frontline therapy. However, up to 30-40% of patients (pts) will experience either relapsed or refractory (R/R) disease. Coventional salvage regimens, such as R-ICE, R-GDP, and R-DHAP achieve an overall response rate (ORR) of 60% and a complete response rate (CR) of 30-40%. Rituximab, in combination with gemcitabine, dexamethasone, cisplatin (R-GDP) offers an established treatment regimen with a manageable side-effect profile, thus providing a viable backbone for innovative treatment combinations. Mitoxantrone hydrochloride liposome (PLM60) is a nano-drug that has been approved as one of the treatment options for relapsed/refractory (r/r) PTCL, and has shown certain efficacy and safety. This study aimed to investigate the efficacy and safety of combining Lipo-MIT with R-GDP in treating r/r DLBCL patients (R-GDPM).

Methods: Eligible pts were ≥ 18y, had histologically conrmed R/R DLBCL by WHO classification, measurable disease by Lugano 2014 criteria, and an ECOG performance status of 0 to 2. Pts were required to have disease progression after ≥1 prior lines of therapy. Pts received R-GDPM regimen (rituximab 375mg/m2, d0; gemcitabine 750-1000mg/m2.d1,d8; dexamethasone 20mg, d1-4; cisplatin 75mg/m2, d1 and Lipo-MIT 18-20mg/m2, d1) every three weeks for 6-8 cycles until disease progression or an intolerable toxic response. The primary endpoint was the overall response rate (ORR), and the secondary endpoints were the complete response (CR), progression free survival (PFS), duration of response (DOR), overall survival (OS) and safety.

Results: Between Aug 2023 and June 2024, the study had enrolled 16 patients. The median age was 62.5 years (range: 33-74 years), with 10 males (62.5%), and 81.3% were advanced stages disease (12.1% of stage III and 69.2% of stage IV.). 12 pts (75%) were at IPI ≥3. The median dose of Lipo-MIT in the regimen was 18mg/m2 (range, 12.5-19.4mg/m2). The cell of origin was germinal center B-cell (GCB) in 4 (25%) pts and non-GCB in 10 (62.5%) pts.The median lines of therapy were 2 (range: 2-3), and all pts had received anthracycline during prior therapy. All of these patients were eligible for efficacy evaluation. Results showed that the best ORR was 75%, CRR was 31.25%. In addition, 4 of the 8 pts with extra-nodal invasion achieved remission (4/8, 50%). Other efficacy indicators such as PFS and OS will be reported after long-term follow-up. Treatment related adverse events (TRAEs) occurred in 12 (75%) pts. The most prevalent grade 3 or higher treatment-related adverse events included neutropenia (n=8, 50.0%), leukopenia (n=8, 50.0%), and lymphopenia (n=5, 31.3%), anemia (n=3, 18.8%), hemoglobinia (n=2, 12.5%) and Infection (n=2, 12.5%). All pts were successfully recoverd from these TRAEs through the implementation of clinical supportive care. There were no treatment-related deaths, adverse cardiac events, pulmonary fibrosis and interstitial pneumonia.

Conclusions: The combination of Lipo-MIT with R-GDP exhibits a favorable safety profile and promising clinical efficacy in patients with r/r DLBCL. The study is ongoing and further results will be continuously released.