Safety and efficacy study of mitoxantrone hydrochloride liposome for pre-treatment bridging of CAR-T therapy in lymphoma
Objective:Chimeric antigen receptor-T(CAR-T)cell therapy has made a breakthrough in the treat-ment of patients with relapsed/refractory lymphoma,and bridging therapy as a regimen for controlling primary disease prior to CAR-T therapy is closely related to the successful infusion and treatment response.This study aimed to evaluate the efficacy and safety of using mitoxantrone hydrochloride liposome to bridge to CAR-T in a retrospective study,providing more options and rationale for clinical practice.Methods:The clinical data of pa-tients who were treated with bridging therapy containing mitoxantrone hydrochloride liposome for CAR-T infusion from March 2022 to April 2024 were retrospectively collected and analyzed.The efficacy evaluation and safety grading was performed with reference to the revised Lugano 2014 criteria,the 2018 ASTCT consensus and the common terminology criteria for adverse events(CTCAE)version 5.0.The transgene copies per microgram of ge-nomic DNA,determined by real-time quantitative polymerase chain reaction,were used as a parameter to assess CAR-T cellular kinetics.Results:A total of 12 patients with relapsed/refractory lymphoma were eventually en-rolled in this study.The median age was 48.5(25.0-67.0)years.Nine cases(75.0％)were diagnosed with re-lapsed/refractory diffuse large B-cell lymphoma,one case was diagnosed Hodgkin lymphoma,one case was diag-nosed Burkitt lymphoma,and one case was diagnosed T-lymphoblastic lymphoma.Eleven patients(91.7％)had advanced-stage Ⅲ-Ⅳ;8 patients(66.7％)had a lymphoma 1PI score of more than 3;7 patients(58.3％)had 2 or more extranodal lesions;and 5 patients(41.7％)had received 3 or more previous treatment lines;8 patients(66.7％)had a bulky disease(≥7.5 cm)or high tumor burden(MTV＞147.5 mL).Among the 11 evaluable pa-tients after CAR-T cell infusion,the objective response rate was 81.8％(9/11),with a complete remission rate of 54.5％(6/11)and a partial remission rate of 27.3％(3/11).Up to April 30,2024,the 1-year progression-free survival rate was 50.0％,with a median progression-free survival of 10.42 months;the 1-year overall survival rate was 61.4％,with a median overall survival not reached.None of the patients in the cohort suffered from im-mune effector cell related neurotoxicity syndrome and≥grade 3 cytokine release syndrome,and the incidence of≥grade 3 hematologic toxicity was 100.0％(neutropenia),91.7％(thrombocytopenia),and 91.7％(anemia),respectively,while the majority of patients(81.8％)recovered to lower than grade 3 hematologic toxicity within 1 month.Conclusion:It indicates that mitoxantrone hydrochloride liposome for bridging to CAR-T therapy shows favorable clinical response and manageable adverse events,suggesting it is a safe and effective option for bridging to CAR-T therapy for a wide range of lymphomas(diffuse large B-cell lymphoma,Hodgkin lymphoma,Burkitt lymphoma,and T-lymphoblastic lymphoma),especially for patients with bulky diseases and/or high tumor burden.
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