Federico Stella, Annalisa Chiappella, Beatrice Casadei, Stefania Bramanti, Silva Ljevar, Patrizia Chiusolo, Alice Di Rocco, Maria C Tisi, Matteo G Carrabba, Ilaria Cutini, Massimo Martino, Anna Dodero, Francesca Bonifazi, Armando Santoro, Federica Sorà, Barbara Botto, Anna M Barbui, Domenico Russo, Maurizio Musso, Giovanni Grillo, Mauro Krampera, Jacopo Olivieri, Marco Ladetto, Federica Cavallo, Massimo Massaia, Luca Arcaini, Martina Pennisi, Pier L Zinzani, Rosalba Miceli, Paolo Corradini
{"title":"A Multicenter Real-life Prospective Study of Axicabtagene Ciloleucel versus Tisagenlecleucel Toxicity and Outcomes in Large B-cell Lymphomas.","authors":"Federico Stella, Annalisa Chiappella, Beatrice Casadei, Stefania Bramanti, Silva Ljevar, Patrizia Chiusolo, Alice Di Rocco, Maria C Tisi, Matteo G Carrabba, Ilaria Cutini, Massimo Martino, Anna Dodero, Francesca Bonifazi, Armando Santoro, Federica Sorà, Barbara Botto, Anna M Barbui, Domenico Russo, Maurizio Musso, Giovanni Grillo, Mauro Krampera, Jacopo Olivieri, Marco Ladetto, Federica Cavallo, Massimo Massaia, Luca Arcaini, Martina Pennisi, Pier L Zinzani, Rosalba Miceli, Paolo Corradini","doi":"10.1158/2643-3230.BCD-24-0052","DOIUrl":null,"url":null,"abstract":"<p><p>This real-world prospective observational study across 21 Italian centers (CART-SIE) compares axicabtagene ciloleucel (axi-cel) and tisagenlecleucel (tisa-cel) outcomes in 485 patients with relapsed/refractory large B-cell lymphoma with baseline characteristics matched by stabilized inverse propensity score weighting. Axi-cel versus tisa-cel had higher all-grade cytokine release syndrome (78.6% vs. 89.3%, P = 0.0017) and neurotoxicity (9.9% vs. 32.2%, P < 0.0001) but also superior progression-free survival (PFS) at 1 year (46.5% vs. 34.1%, P = 0.0009). Even among patients who failed bridging therapy, axi-cel PFS was superior to tisa-cel (37.5% vs. 22.7%, P = 0.0059). Differences in overall survival and high-grade immune toxicities were not significant. The CAR-HEMATOTOX score not only predicted hematologic toxicity but also 1-year survival outcomes (51.5% in CAR-HEMATOTOX high vs. 77.2% in CAR-HEMATOTOX low, P < 0.0001). Twenty patients developed second primary malignancies, including two cases of T-cell neoplasms. These findings enable more informed selection of anti-CD19 CAR T-cell therapy, balancing bridging, safety, and efficacy considerations for individual patients. Significance: The findings of this study on 485 patients with relapsed/refractory large B-cell lymphoma treated with commercial axi-cel and tisa-cel indicate axi-cel's superior PFS after propensity score weighting. The predictive utility of CAR-HEMATOTOX in assessing not only toxicity but also outcomes across both CAR T-cell products may guide future risk-stratified management strategies.</p>","PeriodicalId":29944,"journal":{"name":"Blood Cancer Discovery","volume":null,"pages":null},"PeriodicalIF":11.5000,"publicationDate":"2024-09-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11369587/pdf/","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Blood Cancer Discovery","FirstCategoryId":"1085","ListUrlMain":"https://doi.org/10.1158/2643-3230.BCD-24-0052","RegionNum":0,"RegionCategory":null,"ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"HEMATOLOGY","Score":null,"Total":0}
引用次数: 0
Abstract
This real-world prospective observational study across 21 Italian centers (CART-SIE) compares axicabtagene ciloleucel (axi-cel) and tisagenlecleucel (tisa-cel) outcomes in 485 patients with relapsed/refractory large B-cell lymphoma with baseline characteristics matched by stabilized inverse propensity score weighting. Axi-cel versus tisa-cel had higher all-grade cytokine release syndrome (78.6% vs. 89.3%, P = 0.0017) and neurotoxicity (9.9% vs. 32.2%, P < 0.0001) but also superior progression-free survival (PFS) at 1 year (46.5% vs. 34.1%, P = 0.0009). Even among patients who failed bridging therapy, axi-cel PFS was superior to tisa-cel (37.5% vs. 22.7%, P = 0.0059). Differences in overall survival and high-grade immune toxicities were not significant. The CAR-HEMATOTOX score not only predicted hematologic toxicity but also 1-year survival outcomes (51.5% in CAR-HEMATOTOX high vs. 77.2% in CAR-HEMATOTOX low, P < 0.0001). Twenty patients developed second primary malignancies, including two cases of T-cell neoplasms. These findings enable more informed selection of anti-CD19 CAR T-cell therapy, balancing bridging, safety, and efficacy considerations for individual patients. Significance: The findings of this study on 485 patients with relapsed/refractory large B-cell lymphoma treated with commercial axi-cel and tisa-cel indicate axi-cel's superior PFS after propensity score weighting. The predictive utility of CAR-HEMATOTOX in assessing not only toxicity but also outcomes across both CAR T-cell products may guide future risk-stratified management strategies.
这项跨越 21 个意大利中心的真实世界前瞻性观察研究(CART-SIE)比较了 485 例复发-难治性大 B 细胞淋巴瘤患者的 axicabtagene ciloleucel(axi-cel)和 tisagenlecleucel(tisa-cel)疗效,这些患者的基线特征通过稳定反倾向分数加权法匹配。Axi-cel与tisa-cel相比,具有更高的细胞因子释放综合征(78.6% vs 89.3%,p=0.0017)和神经毒性(9.9% vs 32.2%,p=0.0017)。
期刊介绍:
The journal Blood Cancer Discovery publishes high-quality Research Articles and Briefs that focus on major advances in basic, translational, and clinical research of leukemia, lymphoma, myeloma, and associated diseases. The topics covered include molecular and cellular features of pathogenesis, therapy response and relapse, transcriptional circuits, stem cells, differentiation, microenvironment, metabolism, immunity, mutagenesis, and clonal evolution. These subjects are investigated in both animal disease models and high-dimensional clinical data landscapes.
The journal also welcomes submissions on new pharmacological, biological, and living cell therapies, as well as new diagnostic tools. They are interested in prognostic, diagnostic, and pharmacodynamic biomarkers, and computational and machine learning approaches to personalized medicine. The scope of submissions ranges from preclinical proof of concept to clinical trials and real-world evidence.
Blood Cancer Discovery serves as a forum for diverse ideas that shape future research directions in hematooncology. In addition to Research Articles and Briefs, the journal also publishes Reviews, Perspectives, and Commentaries on topics of broad interest in the field.