Real-life analysis on safety and efficacy of asciminib for ponatinib pretreated patients with chronic myeloid leukemia.
Real-life analysis on safety and efficacy of asciminib for ponatinib pretreated patients with chronic myeloid leukemia.
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对ponatinib预处理慢性髓样白血病患者的安全性和有效性的现实生活分析。
DOI：
10.1007/s00277-022-04932-6
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发表时间：
2022-10
影响因子：
3.5
通讯作者：
Garcia-Gutierrez, V
中科院分区：
文献类型：
--
作者：
Luna, A.;Perez-Lamas, L.;Boque, C.;Giraldo, P.;Xicoy, B.;Ruiz Nuno, C.;Moreno Vega, M.;Alvarez-Larran, A.;Salamanca, A.;Garcia-Noblejas, A.;Vall-Llovera, F.;Villalon, L.;De Las Heras, N.;Ramila, E.;Perez-Encinas, M.;Cuevas, B.;Perez-Lopez, R.;Sanchez-Guijo, F.;Jimenez-Velasco, A.;Lakhwani, S.;Felipe Casado, L.;Rosell, A.;Escola, A.;Fernandez, M. J.;Garcia-Hernandez, C.;Cervero, C.;Mora, E.;Sagues, M.;Suarez-Varela, S.;Velez, P.;Carrascosa Mastell, P.;Bitaube, R. F.;Serrano, L.;Cortes, M.;Vera Goni, J. A.;Steegmann, J. L.;Garcia de Soria, V. Gomez;Alonso-Dominguez, J. M.;Colorado Araujo, M.;Paz Coll, A.;Hernandez-Boluda, J. C.;Garcia-Gutierrez, V
第二代酪氨酸激酶抑制剂（2GTKI）的失败是慢性髓性白血病（CML）患者的一个具有挑战性的情况。Asciminib最近被美国联邦药物管理局批准，在2GTKI失败后的临床试验中显示出良好的疗效和安全性。然而，没有研究专门针对波纳替尼预处理患者（PPT）对阿西米尼的反应率。在这里，我们提供了52例临床实践患者对阿西米尼的反应数据，其中20例（38%）先前有波纳替尼暴露。我们回顾性分析了阿西米尼治疗的反应和毒性，并比较了PPT患者和非PPT患者的结果。中位随访30个月后，34名患者（65%）由于不耐受而改用阿西米尼，18名患者（35%）由于对既往tki的耐药而改用阿西米尼。46例患者（88%）既往至少接受过3次tki。在反应方面，非PPT和PPT患者中分别有74%和53%的患者达到或维持了完全的细胞遗传学反应。较深层的反应，如主要分子反应和4.5分子反应，非PPT组分别为65%和19%，PPT组分别为32%和11%。2例患者（4%）携带T315I突变，均为PPT。在毒性方面，非PPT组3-4级TEAE发生率为22%，PPT组为20%。4例患者（占PPT的20%）出现阿西米尼与波纳替尼的交叉不耐受。我们的数据支持阿西米尼作为耐药和不耐受的非PPT患者以及不耐受PPT患者的有希望的替代方案；耐药PPT亚群仍然是一个具有挑战性的群体，需要进一步的治疗选择。
Failure of second-generation tyrosine kinase inhibitors (2GTKI) is a challenging situation in patients with chronic myeloid leukemia (CML). Asciminib, recently approved by the US Federal Drug Administration, has demonstrated in clinical trials a good efficacy and safety profile after failure of 2GTKI. However, no study has specifically addressed response rates to asciminib in ponatinib pretreated patients (PPT). Here, we present data on responses to asciminib from 52 patients in clinical practice, 20 of them (38%) with prior ponatinib exposure. We analyzed retrospectively responses and toxicities under asciminib and compared results between PPT and non-PPT patients. After a median follow-up of 30 months, 34 patients (65%) switched to asciminib due to intolerance and 18 (35%) due to resistance to prior TKIs. Forty-six patients (88%) had received at least 3 prior TKIs. Regarding responses, complete cytogenetic response was achieved or maintained in 74% and 53% for non-PPT and PPT patients, respectively. Deeper responses such as major molecular response and molecular response 4.5 were achieved in 65% and 19% in non-PPT versus 32% and 11% in PPT, respectively. Two patients (4%) harbored the T315I mutation, both PPT. In terms of toxicities, non-PPT displayed 22% grade 3–4 TEAE versus 20% in PPT. Four patients (20% of PPT) suffered from cross-intolerance with asciminib as they did under ponatinib. Our data supports asciminib as a promising alternative in resistant and intolerant non-PPT patients, as well as in intolerant PPT patients; the resistant PPT subset remains as a challenging group in need of further therapeutic options.
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影响因子：
28.5
作者：
Cortes J;Lang F
通讯作者：
Lang F
影响因子：
20.3
作者：
Rea, Delphine;Mauro, Michael J.;Hochhaus, Andreas
通讯作者：
Hochhaus, Andreas
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Goldman, John M.
通讯作者：
Goldman, John M.
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158.5
作者：
Kantarjian, Hagop;Shah, Neil P.;Baccarani, Michele
通讯作者：
Baccarani, Michele
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作者：
Wylie, Andrew A.;Schoepfer, Joseph;Sellers, William R.
通讯作者：
Sellers, William R.