Brexucabtagene autoleucel in-vivo expansion and BTKi refractoriness have a negative influence on progression-free survival in mantle cell lymphoma: Results from CART-SIE study

IF 5.1 2区 医学 Q1 HEMATOLOGY
Federico Stella, Annalisa Chiappella, Martina Magni, Francesca Bonifazi, Chiara De Philippis, Maurizio Musso, Ilaria Cutini, Silva Ljevar, Anna Maria Barbui, Mirko Farina, Massimo Martino, Massimo Massaia, Giovanni Grillo, Piera Angelillo, Barbara Botto, Francesca Patriarca, Mauro Krampera, Luca Arcaini, Maria Chiara Tisi, Pierluigi Zinzani, Federica Sorà, Stefania Bramanti, Martina Pennisi, Cristiana Carniti, Paolo Corradini
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Abstract

Brexucabtagene autoleucel (brexu-cel) has revolutionized the treatment of patients affected by mantle cell lymphomas. In this prospective, observational multicentre study, we evaluated 106 patients, with longitudinal brexu-cel kinetics in peripheral blood monitored in 61 of them. Clinical outcomes and toxicities are consistent with previous real-world evidence studies. Notably, beyond established poor prognostic factors—such as blastoid variant and elevated lactate dehydrogenase—Bruton tyrosine-kinase inhibitors (BTKi) refractoriness and platelet count emerged as significant predictors of survival. Specifically, the 1-year overall survival was 56% in BTKi-refractory patients compared to 92% in BTKi-relapsed patients (p = 0.0001). Our study also demonstrated that in-vivo monitoring of brexu-cel expansion is feasible and correlates with progression-free survival and toxicities. Progression-free survival at 1 year was 74% in patients categorized as strong expanders, based on brexu-cel peak concentration, versus 54% in poor expanders (p = 0.02). Furthermore, in-vivo expansion helped identify a high-risk group of non-responders, those with progressive or stable disease at the 90-day post-infusion evaluation (OR = 4.7, 95% CI = 1.1–34, p = 0.04) characterized by dismal outcomes. When integrated with other clinical factors, monitoring brexu-cel expansion could assist in recognizing patients at high risk of early relapse.

Abstract Image

来自CART-SIE研究的结果:Brexucabtagene自体甲醇体内扩增和BTKi难治性对套细胞淋巴瘤的无进展生存期有负面影响。
Brexucabtagene (brexuctagene)已经彻底改变了套细胞淋巴瘤患者的治疗方法。在这项前瞻性、观察性的多中心研究中,我们评估了106例患者,其中61例患者监测了外周血纵向brexucell动力学。临床结果和毒性与先前的真实世界证据研究一致。值得注意的是,除了已确定的不良预后因素(如囊胚变异和乳酸脱氢酶-布鲁顿酪氨酸激酶抑制剂(BTKi)升高)外,难愈性和血小板计数成为生存的重要预测因素。具体而言,btki难治性患者的1年总生存率为56%,而btki复发患者为92% (p = 0.0001)。我们的研究还表明,体内监测brexuus - cell扩张是可行的,并且与无进展生存和毒性相关。根据细胞峰值浓度,强扩张剂组1年无进展生存率为74%,而弱扩张剂组为54% (p = 0.02)。此外,体内扩展有助于确定无反应的高风险组,即在输注后90天评估时疾病进展或稳定的患者(or = 4.7, 95% CI = 1.1-34, p = 0.04),其结果令人堪堪性。当与其他临床因素相结合时,监测brexucell的扩张可以帮助识别早期复发的高危患者。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
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来源期刊
CiteScore
8.60
自引率
4.60%
发文量
565
审稿时长
1 months
期刊介绍: The British Journal of Haematology publishes original research papers in clinical, laboratory and experimental haematology. The Journal also features annotations, reviews, short reports, images in haematology and Letters to the Editor.
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