初诊费城染色体阳性急性淋巴细胞白血病患者无疾病或毒性症状的质量调整时间（Q-TWiST）：波纳替尼与伊马替尼的比较

Quality-Adjusted Time Without Symptoms of Disease or Toxicity (Q-TWiST) in Patients With Newly Diagnosed Philadelphia Chromosome-Positive Acute Lymphoblastic Leukemia: A Comparison of Ponatinib Versus Imatinib.

作者信息

Ashaye Ajibade, Shi Ling, Aldoss Ibrahim, Montesinos Pau, Vachhani Pankit, Rocha Vanderson, Papayannidis Cristina, Leonard Jessica T, Baer Maria R, Ribera Jose-Maria, McCloskey James, Wang Jianxiang, Rane Deepali, Guo Shien

机构信息

Takeda Development Center Americas Inc., Cambridge, Massachusetts, USA.

Evidera Inc., Bethesda, Maryland, USA.

出版信息

Cancer Med. 2025 Apr;14(7):e70780. doi: 10.1002/cam4.70780.

DOI:10.1002/cam4.70780

PMID:40165400

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11958597/

Abstract

BACKGROUND

In the phase 3 ponatinib-3001 trial (PhALLCON, NCT03589326), ponatinib demonstrated superior efficacy over imatinib with comparable safety in patients with newly diagnosed Philadelphia-positive acute lymphoblastic leukemia (Ph+ ALL). This post hoc analysis evaluated the net benefits of ponatinib using a quality-adjusted time without symptoms of disease or toxicity (Q-TWiST) approach.

METHODS

Overall survival (OS) time for patients from PhALLCON was partitioned into three health states: TOX (time with grade 3+ treatment-emergent adverse events [TEAEs] before disease progression), TWiST (time without toxicity before progression), and REL (time from progression until death or end of follow-up). Q-TWiST was calculated as the sum of health utility-weighted restricted mean durations of the three states. A relative Q-TWiST gain of ≥ 10% was considered clinically important. Sensitivity analyses were conducted by varying TOX and REL utilities, follow-up time, and the TOX definition (using grade 2+ TEAEs or patient-perceived treatment tolerability assessed by the FACT-GP5).

RESULTS

Among all randomized patients (ponatinib n = 164, imatinib n = 81), restricted mean OS was similar between arms (1082.2 vs. 1024.8 days; p = 0.373). In the base-case analysis, mean TWiST was 214.5 days longer with ponatinib versus imatinib (95% CI 70.3-358.7; p = 0.004), REL was shorter by 175.9 days (325.4-26.5; p = 0.021), and TOX was not significantly different between arms (p = 0.228). The relative Q-TWiST gain (10.98%) was clinically important. Sensitivity analyses consistently supported the robustness of the base-case findings.

CONCLUSION

Ponatinib may prolong quality-adjusted survival compared with imatinib, supporting the benefit-risk profile of ponatinib as a front-line treatment for Ph+ ALL.

TRIAL REGISTRATION

NCT03589326.

摘要

背景

在3期波纳替尼-3001试验（PhALLCON，NCT03589326）中，对于新诊断的费城染色体阳性急性淋巴细胞白血病（Ph+ ALL）患者，波纳替尼显示出优于伊马替尼的疗效，且安全性相当。这项事后分析采用质量调整无疾病或毒性症状时间（Q-TWiST）方法评估了波纳替尼的净效益。

方法

将来自PhALLCON试验患者的总生存期（OS）分为三种健康状态：TOX（疾病进展前3级及以上治疗引发不良事件[TEAE]的时间）、TWiST（进展前无毒性的时间）和REL（从进展到死亡或随访结束的时间）。Q-TWiST计算为这三种状态的健康效用加权受限平均持续时间之和。相对Q-TWiST增益≥10%被认为具有临床意义。通过改变TOX和REL效用、随访时间以及TOX定义（使用2级及以上TEAE或通过FACT-GP5评估的患者感知治疗耐受性）进行敏感性分析。

结果

在所有随机分组的患者中（波纳替尼组n = 164，伊马替尼组n = 81），两组的受限平均OS相似（1082.2天对1024.8天；p = 0.373）。在基础分析中，与伊马替尼相比，波纳替尼的平均TWiST长214.5天（95% CI 70.3 - 358.7；p = 0.004），REL短175.9天（325.4 - 26.5；p = 0.021），两组间TOX无显著差异（p = 0.228）。相对Q-TWiST增益（10.98%）具有临床意义。敏感性分析一致支持基础分析结果的稳健性。