在综合癌症中心治疗的急性淋巴细胞白血病患者中，采用一线基于 Hyper-CVAD 的方案（包括 Hyper-CVAD 加 ponatinib）的临床经验。

Clinical experience with frontline Hyper-CVAD-based regimens, including Hyper-CVAD plus ponatinib, in patients with acute lymphoblastic leukemia treated at a comprehensive cancer center.

机构信息

Department of Internal Medicine, Division of Hematology and Oncology, University of California Davis School of Medicine, Sacramento, CA, USA.

Pharmacy Department, University of California Davis School of Medicine, Sacramento, CA, USA.

出版信息

Leuk Res. 2022 Aug;119:106885. doi: 10.1016/j.leukres.2022.106885. Epub 2022 Jun 8.

DOI:10.1016/j.leukres.2022.106885

PMID:35738024

Abstract

BACKGROUND

Hyper-CVAD is an established regimen for adult ALL that was developed at the MD Anderson Cancer Center (MDACC). However, results can vary across different institutions given the heterogeneity of patient populations and institutional practices. Moreover, while a MDACC study demonstrated that the combination of ponatinib plus hyper-CVAD produced remarkable activity in untreated Ph+ ALL, it remains to be externally validated. We sought to validate those findings in previously untreated adult patients with Ph+ ALL.

METHODS

This was a retrospective study analyzing the outcomes of previously untreated adult ALL patients treated with hyper-CVAD, with a focus on Ph+ ALL patients treated with ponatinib plus hyper-CVAD.

RESULTS

82 patients were included. The median age was 51 years. The median follow-up was 2.62 years. The 5-year overall survival (OS) and event-free survival (EFS) were 39.5 % and 28.2 %, respectively. For Ph+ ALL patients (n = 13) receiving ponatinib plus hyper-CVAD, 3-year OS and EFS were both 92.3 %. Univariate analysis showed a high WBC and poor-risk cytogenetics to be associated with inferior outcomes, while CD20 + predicted favorable outcomes in B-ALL patients. On multivariate analysis, CD20 + retained significance for Philadelphia-negative (Ph-) ALL. For Ph+ ALL, ponatinib was associated with better OS and EFS on univariate and multivariate analysis.

CONCLUSION

Our data supports the use of ponatinib plus hyper-CVAD as a standard of care regimen for Ph+ ALL. Our outcomes for Ph-ALL and T-cell ALL (T-ALL) show that advances are still needed in the frontline setting, and clinical trial enrollment is recommended.

摘要

背景

Hyper-CVAD 是一种已在 MD 安德森癌症中心（MDACC）开发的用于成人 ALL 的既定方案。然而，由于患者人群的异质性和机构实践的不同，结果可能因机构而异。此外，尽管 MDACC 的一项研究表明，ponatinib 联合 hyper-CVAD 可在未经治疗的 Ph+ALL 中产生显著活性，但仍需外部验证。我们试图在未经治疗的成人 Ph+ALL 患者中验证这些发现。

方法

这是一项回顾性研究，分析了接受 hyper-CVAD 治疗的未经治疗的成人 ALL 患者的结果，重点是接受 ponatinib 联合 hyper-CVAD 治疗的 Ph+ALL 患者。

结果

共纳入 82 例患者。中位年龄为 51 岁。中位随访时间为 2.62 年。5 年总生存率（OS）和无事件生存率（EFS）分别为 39.5%和 28.2%。接受 ponatinib 联合 hyper-CVAD 治疗的 13 例 Ph+ALL 患者的 3 年 OS 和 EFS 均为 92.3%。单因素分析显示，高白细胞计数和不良细胞遗传学与较差的结果相关，而 CD20+在 B-ALL 患者中预测良好的结果。多因素分析显示，CD20+在 Ph-ALL 中仍具有显著意义。对于 Ph+ALL，ponatinib 在单因素和多因素分析中均与更好的 OS 和 EFS 相关。