英国利兹大学Peter Hillmen团队研究了可测量残余病灶指导慢性淋巴细胞白血病治疗的疗效。相关论文于2023年12月10日发表在《新英格兰医学杂志》上。

与化学免疫疗法相比，伊布替尼和维奈托克的组合已被证明可以改善慢性淋巴细胞白血病（CLL）患者的预后。目前尚不清楚伊布替尼-维奈托克联合根据可测量残余病灶（MRD）个性化治疗的持续时间是否比氟达拉滨-环磷酰胺-利妥昔单抗（FCR）更有效。

在这项涉及初治CLL患者的临床3期、多中心、随机、对照、开放标签平台试验中，研究比较了伊布替尼-维奈托克和伊布替尼单药治疗与FCR的治疗效果。在伊布替尼-维奈托克组中，伊布替尼治疗2个月后，加入维奈托克进行长达6年的治疗。通过在外周血和骨髓中评估的MRD来确定伊布替尼-维奈托克治疗的持续时间，且达到不可检测MRD所需时间的两倍。主要终点是与FCR组相比，伊布替尼-维奈托克组的无进展生存率。关键次要终点是总生存率、缓解率、MRD和安全性。

共有523名患者被随机分配到伊布替尼-维奈托克组或FCR组。在中位43.7个月时，伊布替尼-维奈托克组的12名患者和FCR组的75名患者出现了疾病进展或死亡（危险比为0.13；P<0.001）。伊布替尼-维奈托克组有9名患者死亡，FCR组有25名患者死亡（危险比为0.31）。3年时，伊布替尼-维奈托克组58.0%的患者因MRD检测不到而停止治疗。经过5年的伊布替尼-维奈托克治疗，65.9%的患者骨髓中MRD检测不到，92.7%的患者外周血中MRD也检测不到。伊布替尼-维奈托克组和FCR组的感染风险相似。伊布替尼-维奈托克组发生心脏严重不良事件的患者比例高于FCR组（10.7%对0.4%）。

研究结果表明，与FCR相比，MRD指导的伊布替尼-维奈托克提高了无进展生存率，总生存率的结果也有利于伊布替尼-维奈托克。

附：英文原文

Title: Chronic Lymphocytic Leukemia Therapy Guided by Measurable Residual Disease | NEJM

Author: anonymous

Issue&Volume: 2023-12-10

Abstract:

Background

The combination of ibrutinib and venetoclax has been shown to improve outcomes in patients with chronic lymphocytic leukemia (CLL) as compared with chemoimmunotherapy. Whether ibrutinib–venetoclax and personalization of treatment duration according to measurable residual disease (MRD) is more effective than fludarabine–cyclophosphamide–rituximab (FCR) is unclear.

Methods

In this phase 3, multicenter, randomized, controlled, open-label platform trial involving patients with untreated CLL, we compared ibrutinib–venetoclax and ibrutinib monotherapy with FCR. In the ibrutinib–venetoclax group, after 2 months of ibrutinib, venetoclax was added for up to 6 years of therapy. The duration of ibrutinib–venetoclax therapy was defined by MRD assessed in peripheral blood and bone marrow and was double the time taken to achieve undetectable MRD. The primary end point was progression-free survival in the ibrutinib–venetoclax group as compared with the FCR group, results that are reported here. Key secondary end points were overall survival, response, MRD, and safety.

Results

A total of 523 patients were randomly assigned to the ibrutinib–venetoclax group or the FCR group. At a median of 43.7 months, disease progression or death had occurred in 12 patients in the ibrutinib–venetoclax group and 75 patients in the FCR group (hazard ratio, 0.13; 95% confidence interval [CI], 0.07 to 0.24; P<0.001). Death occurred in 9 patients in the ibrutinib–venetoclax group and 25 patients in the FCR group (hazard ratio, 0.31; 95% CI, 0.15 to 0.67). At 3 years, 58.0% of the patients in the ibrutinib–venetoclax group had stopped therapy owing to undetectable MRD. After 5 years of ibrutinib–venetoclax therapy, 65.9% of the patients had undetectable MRD in the bone marrow and 92.7% had undetectable MRD in the peripheral blood. The risk of infection was similar in the ibrutinib–venetoclax group and the FCR group. The percentage of patients with cardiac severe adverse events was higher in the ibrutinib–venetoclax group than in the FCR group (10.7% vs. 0.4%).

Conclusions

MRD-directed ibrutinib–venetoclax improved progression-free survival as compared with FCR, and results for overall survival also favored ibrutinib–venetoclax.

DOI: 10.1056/NEJMoa2310063

Source: https://www.nejm.org/doi/full/10.1056/NEJMoa2310063