Department of Cardiology, Boston Children's Hospital and Harvard Medical School, Boston, MA.
Division of Pediatric Medical Neuro-Oncology, Dana-Farber Cancer Institute, Boston Children's Hospital and Harvard Medical School, Boston, MA; Department of Hematology/Oncology, Boston Children's Hospital and Harvard Medical School, Boston, MA.
J Pediatr. 2018 Jul;198:29-35.e5. doi: 10.1016/j.jpeds.2018.01.029. Epub 2018 Mar 23.
To evaluate the use of imatinib mesylate with or without bevacizumab targeting neoproliferative myofibroblast-like cells with tyrosine kinase receptor expression, as adjuncts to modern interventional therapies for the treatment of multivessel intraluminal pulmonary vein stenosis (PVS). We describe the 48- and 72-week outcomes among patients receiving imatinib mesylate with or without bevacizumab for multivessel intraluminal PVS.
This single-arm, prospective, open-label US Food and Drug Administration approved trial enrolled patients with ≥2 affected pulmonary veins after surgical or catheter-based relief of obstruction between March 2009 and December 2014. Drug therapy was discontinued at 48 weeks, or after 24 weeks of stabilization, whichever occurred later.
Among 48 enrolled patients, 5 had isolated PVS, 26 congenital heart disease, 5 lung disease, and 12 both. After the 72-week follow-up, 16 patients had stabilized, 27 had recurred locally without stabilization, and 5 had progressed. Stabilization was associated with the absence of lung disease (P = .03), a higher percentage of eligible drug doses received (P = .03), and was not associated with age, diagnosis, disease laterality, or number of veins involved. Survival to 72 weeks was 77% (37 of 48). Adverse events were common (n = 1489 total), but only 16 were definitely related to drug treatment, none of which were serious.
Survival to 72 weeks was 77% in a referral population with multivessel intraluminal PVS undergoing multimodal treatment, including antiproliferative tyrosine kinase blockade. Toxicity specific to tyrosine kinase blockade was minimal.
评估甲磺酸伊马替尼与贝伐单抗联合使用或不联合使用，靶向表达酪氨酸激酶受体的新生增生性肌纤维母细胞样细胞，作为现代介入治疗多血管腔内肺静脉狭窄（PVS）的辅助手段。我们描述了接受甲磺酸伊马替尼联合或不联合贝伐单抗治疗多血管腔内 PVS 的患者在 48 周和 72 周时的结果。
这是一项单臂、前瞻性、开放标签的美国食品和药物管理局批准的试验，招募了 2009 年 3 月至 2014 年 12 月间手术或导管解除梗阻后至少有 2 条受累肺静脉的患者。药物治疗在 48 周或在 24 周稳定后停药，以先发生者为准。
在 48 名入组患者中，5 例为孤立性 PVS，26 例为先天性心脏病，5 例为肺部疾病，12 例为两者兼有。在 72 周随访后，16 例患者稳定，27 例局部复发但未稳定，5 例进展。稳定与无肺部疾病（P = 0.03）、接受更多合格药物剂量（P = 0.03）有关，与年龄、诊断、疾病侧别或受累静脉数量无关。72 周时的生存率为 77%（48 例中的 37 例）。不良事件很常见（总共有 1489 例），但只有 16 例与药物治疗肯定有关，且均不严重。
在多血管腔内 PVS 接受多模式治疗（包括抗增殖酪氨酸激酶阻断）的转诊人群中，72 周时的生存率为 77%。针对酪氨酸激酶阻断的特异性毒性最小。
