波纳替尼与阿西替尼在慢性期慢性髓性白血病第二代酪氨酸激酶抑制剂治疗后的疗效比较：匹配调整间接比较

Ponatinib vs. asciminib in post-second-generation tyrosine kinase inhibitor therapy for chronic-phase chronic myeloid leukemia: a matching-adjusted indirect comparison.

作者信息

Garcia-Gutierrez Valentin, Huang Fei, Ashaye Ajibade, Dalal Mehul, Laliman-Khara Victor, Breccia Massimo, Rutherford Megan, Moradian Hoora, Patos Petros, Jabbour Elias Joseph

机构信息

Ramón y Cajal University Hospital, Instituto Ramón y Cajal de Investigación Sanitaria (IRYCIS), Universidad de Alcalá, Madrid, Spain.

Global Evidence and Outcomes Oncology, Takeda Development Center Americas, Inc, Lexington, MA, United States.

出版信息

Front Oncol. 2024 Nov 20;14:1455378. doi: 10.3389/fonc.2024.1455378. eCollection 2024.

DOI:10.3389/fonc.2024.1455378

PMID:39634261

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11615674/

Abstract

BACKGROUND

Ponatinib and asciminib are approved for third-line therapy in chronic-phase chronic myeloid leukemia (CP-CML) and are the only drugs approved for patients with the T315I mutation in the United States. In Europe, only ponatinib is approved for patients with the T315I mutation.

METHODS

Clinical trials evaluating ponatinib or asciminib in patients with relapsed and refractory (R/R) CP-CML who failed one or more second-generation TKIs or had the T315I mutation were identified in a systematic review of medical literature databases. A matching-adjusted indirect comparison (MAIC) analysis with individual patient-level data with ponatinib was used to balance baseline characteristics between ponatinib and asciminib groups. After matching, the response rate was calculated using the MAIC weight for each patient and the difference in response rate was calculated using a two-independent proportion Z-test. Cumulative rates of ≤1% and major molecular response (MMR) in patients without baseline response were compared. Patients were further stratified by T315I mutation status.

RESULTS

The MAIC included four trials (ponatinib: NCT02467270, NCT01207440; asciminib: NCT02081378, NCT03106779). In patients without baseline response of ≤1%, the adjusted ≤1% rate difference with ponatinib vs. asciminib was 9.33% (95% confidence interval [CI]: 0.79%-17.86%; adjusted MMR rate difference: 6.84% [95% CI: -0.95%-14.62%]) by 12 months in favor of ponatinib. In patients with the T315I mutation, adjusted ≤1% rate difference with ponatinib vs. asciminib was 43.54% (95% CI: 22.20%-64.87%; adjusted MMR rate difference: 47.37% [95% CI: 28.72%-66.02%]) by 12 months.

CONCLUSION

After key baseline characteristics adjustment, cumulative ≤1% and MMR rates were statistically higher with ponatinib than asciminib in patients without a baseline response in most of the comparisons by 12 months. Favorable efficacy outcomes observed in ponatinib vs. asciminib were consistently stronger in the T315I mutation subgroup.

摘要

背景

波纳替尼和阿西替尼被批准用于慢性期慢性髓性白血病（CP-CML）的三线治疗，且是美国仅有的被批准用于T315I突变患者的药物。在欧洲，仅波纳替尼被批准用于T315I突变患者。

方法

在对医学文献数据库的系统评价中，识别出评估波纳替尼或阿西替尼用于一线或更多二代酪氨酸激酶抑制剂（TKIs）治疗失败或存在T315I突变的复发难治性（R/R）CP-CML患者的临床试验。使用对波纳替尼个体患者水平数据进行匹配调整的间接比较（MAIC）分析，平衡波纳替尼组和阿西替尼组之间的基线特征。匹配后，使用每位患者的MAIC权重计算缓解率，并使用两独立样本率Z检验计算缓解率差异。比较无基线缓解患者中≤1%的累积率和主要分子缓解（MMR）。患者进一步按T315I突变状态分层。

结果

MAIC纳入四项试验（波纳替尼：NCT02467270、NCT01207440；阿西替尼：NCT02081378、NCT03106779）。在无基线≤1%缓解的患者中，到12个月时，波纳替尼与阿西替尼相比，调整后的≤1%率差异为9.33%（95%置信区间[CI]：0.79%-17.86%；调整后的MMR率差异：6.84%[95%CI：-0.95%-14.62%]），波纳替尼更具优势。在T315I突变患者中，到12个月时，波纳替尼与阿西替尼相比，调整后的≤1%率差异为43.54%（95%CI：22.20%-64.87%；调整后的MMR率差异：47.37%[95%CI：28.72%-66.02%]）。