添加Venetoclax至hyper-CVAD、Nelarabine及聚乙二醇化天冬氨酸酶治疗T细胞急性淋巴细胞白血病和淋巴瘤患者的2期临床试验的纵向随访

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

LEUKEMIA

影响因子:13.4

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

DOI: 10.1038/s41375-024-02414-4

摘要

合理使用活性药物于T细胞急性淋巴细胞白血病/淋巴瘤（T-ALL/LBL）一线治疗中，有助于改善预后。本文报道了HyperCVAD联合Nelarabine和聚乙二醇化天冬氨酸酶（原始队列）2期试验的长期随访。在最新的方案中，添加了Venetoclax到诱导/巩固方案中（Venetoclax队列）。符合条件的患者为未治疗的T-ALL/LBL成人或经过微量治疗后且器官功能充分的患者。本分析的主要终点是通过加入Venetoclax改善2年无进展生存（PFS）和总生存（OS）。从2007年8月至2024年12月，共145例患者接受治疗，中位年龄为35.4岁，其中46例（33.8%）属于Venetoclax队列。在中位随访62.4个月时，5年PFS、缓解持续时间（DOR）和OS分别为63.7%、72.0%和66.2%。在Venetoclax队列（中位随访24.4个月）中，2年PFS（87.9%对比64.1%，p=0.03）和2年DOR（93.6%对比69.2%，p=0.005）优于原始队列（中位随访89.4个月），而2年OS显示趋势更佳（87.8%对比73.9%，p=0.16）。发热性中性粒细胞减少症为最常见的严重不良事件，发生在60%的患者中。添加Venetoclax到HyperCVAD-Nelarabine-聚乙二醇化天冬氨酸酶方案中具有耐受性，并改善了DOR和PFS。

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.