【編者按】NEJM Quick Take以動畫形式，在2分鐘內介紹一篇最新NEJM論著。《NEJM醫學前沿》每周六同步更新當期NEJM論著的視頻總結並配以中文字幕，讓讀者迅速掌握文章的精髓，練習聽力和發音。點擊「閱讀原文」，閱讀對應NEJM論著。
達沙替尼-倍林妥莫雙抗用於費城染色體陽性急性淋巴細胞白血病的一線治療Dasatinib–Blinatumomab Front-Line Treatment for Ph-Positive Acute Lymphoblastic Leukemia朗讀者：Dr. Stephen Morrissey, NEJM執行主編在費城染色體陽性ALL成人患者中，使用ABL特異性TK抑制劑（聯合或不聯合全身性化療）可使大多數患者達到完全血液學緩解；微小殘留病變持續減少與治癒概率增加相關。短視頻中總結了新的研究發現。達沙替尼-倍林妥莫雙抗治療成人費城染色體陽性急性淋巴細胞白血病
Dasatinib–Blinatumomab for Ph-Positive Acute Lymphoblastic Leukemia in Adults
背景
酪氨酸激酶抑制劑已改善了費城染色體陽性急性淋巴細胞白血病（ALL）患者的結局。分子學緩解是主要治療目標。Outcomes in patients with Philadelphia chromosome (Ph)–positive acute lymphoblastic leukemia (ALL) have improved with the use of tyrosine kinase inhibitors. Molecular remission is a primary goal of treatment.方法
我們在新診斷為費城染色體陽性ALL的成人患者（無年齡上限）中對一線治療開展了一項2期單組試驗。本試驗給予患者達沙替尼+糖皮質激素治療，之後給予兩個周期的倍林妥莫雙抗（blinatumomab）治療。主要終點是治療後骨髓內的持續分子學緩解。We conducted a phase 2 single-group trial of first-line therapy in adults with newly diagnosed Ph-positive ALL (with no upper age limit). Dasatinib plus glucocorticoids were administered, followed by two cycles of blinatumomab. The primary end point was a sustained molecular response in the bone marrow after this treatment.結果
在本試驗納入的63例患者（中位年齡，54歲；範圍，24~82）中，98%達到了完全緩解。達沙替尼誘導治療結束時（第85日），29%的患者達到了分子學緩解，經過兩個周期倍林妥莫雙抗治療後，這一百分比提高至60%；經過更多周期倍林妥莫雙抗治療後，達到分子學緩解的患者百分比進一步提高。中位隨訪18個月後，總生存率為95%，無病生存率為88%；在有IKZF1缺失+其他遺傳畸變（CDKN2A或CDKN2B、PAX5或這兩者[即IKZF1plus]）的患者中，無病生存率較低。在誘導治療期間微小殘留病變增多的6例患者中，我們檢測到ABL1突變，而且所有這些突變均被倍林妥莫雙抗清除。有6例患者復發。本試驗共記錄到21起3級或更高級別的不良事件。共計24例患者接受了異基因幹細胞移植，有1例死亡與移植相關（4%）。
Result
Of the 63 patients (median age, 54 years; range, 24 to 82) who were enrolled, a complete remission was observed in 98%. At the end of dasatinib induction therapy (day 85), 29% of the patients had a molecular response, and this percentage increased to 60% after two cycles of blinatumomab; the percentage of patients with a molecular response increased further after additional blinatumomab cycles. At a median follow-up of 18 months, overall survival was 95% and disease-free survival was 88%; disease-free survival was lower among patients who had an IKZF1 deletion plus additional genetic aberrations (CDKN2A or CDKN2B, PAX5, or both [i.e., IKZF1plus]). ABL1 mutations were detected in 6 patients who had increased minimal residual disease during induction therapy, and all these mutations were cleared by blinatumomab. Six relapses occurred. Overall, 21 adverse events of grade 3 or higher were recorded. A total of 24 patients received a stem-cell allograft, and 1 death was related to transplantation (4%).
結論
在費城染色體陽性ALL成人患者中，基於靶向治療和免疫治療策略，採用達沙替尼和倍林妥莫雙抗，不包含化療的誘導和鞏固一線治療達到了較高的分子學緩解率和生存率，且3級或更高級別毒性作用很少。（由義大利癌症研究會[Associazione Italiana per la Ricerca sul Cancro]等資助；GIMEMA LAL2116 D-ALBA在EudraCT註冊號為2016-001083-11；在ClinicalTrials.gov註冊號為NCT02744768。）
Conclusions
A chemotherapy-free induction and consolidation first-line treatment with dasatinib and blinatumomab that was based on a targeted and immunotherapeutic strategy was associated with high incidences of molecular response and survival and few toxic effects of grade 3 or higher in adults with Ph-positive ALL. (Funded by Associazione Italiana per la Ricerca sul Cancro and others; GIMEMA LAL2116 D-ALBA EudraCT number, 2016-001083-11; ClinicalTrials.gov number, NCT02744768.)
Robin Foà, Renato Bassan, Antonella Vitale, et al. Dasatinib–Blinatumomab for Ph-Positive Acute Lymphoblastic Leukemia in Adults. DOI:10.1056/NEJMoa2016272關注《NEJM醫學前沿》
版權資訊
本文由《NEJM醫學前沿》編輯部負責翻譯、編寫或約稿。對於源自NEJM集團旗下英文產品的翻譯和編寫文章，內容請以英文原版為準。中譯全文以及所含圖表等，由麻薩諸塞州醫學會NEJM集團獨家授權。如需轉載，請聯繫nejmqianyan@nejmqianyan.cn。未經授權的翻譯是侵權行為，版權方保留追究法律責任的權利。