在T-Cell急性淋巴细胞性白血病和淋巴瘤的患者中，添加到高cVAD，Nelarabine和Pegypated天冬酰胺酶的Venetoclax的2期试验的纵向随访中
Longitudinal follow up of a phase 2 trial of venetoclax added to hyper-CVAD, nelarabine and pegylated asparaginase in patients with T-cell acute lymphoblastic leukemia and lymphoma
影响因子:13.40000
分区:医学1区 Top / 血液学1区 肿瘤学2区
发表日期:2024 Dec
作者:
Farhad Ravandi, Jayastu Senapati, Nitin Jain, Nicholas J Short, Tapan Kadia, Gautam Borthakur, Marina Konopleva, William Wierda, Xuelin Huang, Abhishek Maiti, Ghayas Issa, Hayley Balkin, Rebecca Garris, Alessandra Ferrajoli, Guillermo Garcia-Manero, Yesid Alvarado, Partow Kebriaei, Elias Jabbour, Hagop M Kantarjian
摘要
在T细胞急性淋巴细胞白血病/淋巴瘤（T-ALL/LBL）中，有活性药物的最佳前线使用谨慎地改善预后。我们报告了Nelarabine和Pegypated天冬氨酸酶（原始队列）的HyperCVAD 2期试验的长期随访。在最新的方案中，迭代次数添加到感应/巩固方案（Venetoclax队列）中。符合条件的患者是未经治疗的T-ALL/LBL或最少治疗后的成年人，并具有足够的器官功能。该分析的主要终点是与Venetoclax的2年无进展生存率（PFS）和总生存期（OS）改善。从2007年8月到2024年12月，145例中位年龄为35.4岁的患者接受治疗； 46（33.8％）在Venetoclax队列中。在62.4个月的中位随访（MFU），5年PFS，响应持续时间（DOR）和OS分别为63.7％，72.0％和66.2％。在Venetoclax队列（MFU 24.4个月）中，2年PFS（87.9％对64.1％，P = 0.03）和2年DOR（93.6％对69.2％，P = 0.005）优于原始队列（MFU 89.4个月）和2年OS的原始队列（89.4％）更好（87.8％5.8％5.8％vers 7.8％vers vers vers vers vers vers vers vers vers vers vers vers pers pers pers pers pers pers 7.8％，pers pers pers pers 7.8％，pers pers pers pers 7.8％，pers pers pers 7.8％，pers 7.8％。热中性粒细胞减少是最常见的严重不良事件，在60％的患者中可见。在甲状腺素甲苯滨 - 垂氨酸半冬酸酯中添加静脉藻是可以忍受的，并且导致了DOR和PFS的改善。
Abstract
Optimal frontline use of active agents in T-cell acute lymphoblastic leukemia/lymphoma (T-ALL/LBL) is prudent to improve outcomes. We report the long-term follow-up of the phase 2 trial of HyperCVAD with nelarabine and pegylated asparaginase (Original cohort). In the latest protocol iteration venetoclax was added to the induction/consolidation regimen (Venetoclax cohort). Eligible patients were adults with untreated T-ALL/LBL or after minimal therapy and with adequate organ function. Primary endpoint of this analysis was improvement in 2-year progression free survival (PFS) and overall survival (OS) with venetoclax. From Aug 2007 to Dec 2024, 145 patients, at a median age of 35.4 years, were treated; 46 (33.8%) were in the venetoclax cohort. At median follow-up (mFU) of 62.4 months, 5-year PFS, duration of response (DOR), and OS were 63.7%, 72.0% and 66.2% respectively. In the venetoclax cohort (mFU 24.4 months) 2-year PFS (87.9% versus 64.1%, p = 0.03) and 2-year DOR (93.6% versus 69.2%, p = 0.005) were superior to the original cohort (mFU 89.4 months) and 2-year OS appeared better (87.8% versus 73.9%, p = 0.16). Febrile neutropenia was the most common serious adverse event, seen in 60% patients. The addition of venetoclax to HyperCVAD-nelarabine-pegylated asparaginase was tolerable and led to improvement in DOR and PFS.