Acalabrutinib, venetoclax, and obinutuzumab as frontline treatment for chronic lymphocytic leukaemia: a single-arm,-label, 2
Acalabrutinib, venetoclax, and obinutuzumab as frontline treatment for chronic lymphocytic leukaemia: a single-arm,-label, 2
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DOI：
10.1016/s1470-2045(21)00455-1
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发表时间：
2021-09-27
期刊：
影响因子：
51.1
通讯作者：
Brown, Jennifer R.
中科院分区：
文献类型：
--
作者：
Davids, Matthew S.;Lampson, Benjamin L.;Brown, Jennifer R.
acalabrutinib连续治疗和venetoclax-obinutuzumab固定持续时间治疗对既往未经治疗的慢性淋巴细胞白血病均有效。我们假设一线时限、微小残留病（MRD）指导的acalabrutinib、venetoclax和obinutuzumab三联疗法将诱导深度（即更多患者的MRD检测不到）和持久缓解。方法在这项开放标签、单组、制药商申办的2期研究中，从美国马萨诸塞州波士顿的两家学术医院招募慢性淋巴细胞白血病或小淋巴细胞淋巴瘤患者。符合条件的患者年龄≥ 18岁，东部肿瘤协作组体能状态评分为0-2，且未接受过治疗。患者以28天为一个周期进行治疗。Acalabrutinib单药治疗，第1周期口服100 mg，每日2次，然后与静脉注射obinutuzumab联合治疗6个周期（第2周期第1天100 mg，第2天900 mg，第8天1000 mg，第15天和第3-7周期第1天1000 mg）;并且从第4周期开始，使用从第1天的20 mg加速增加到第22天的400 mg的剂量，每天口服维奈托克，并且此后继续以该剂量给药。患者继续接受acalabrutinib 100 mg每日2次和venetoclax 400 mg每日1次治疗，直至第16周期第1天或第25周期第1天。如果患者在骨髓中检测不到MRD，则可选择在第16周期开始时（如果也处于完全缓解状态）或第25周期开始时（如果至少处于部分缓解状态）停止治疗。主要终点是骨髓中检测不到MRD的完全缓解（定义为
Background Both continuous therapy with acalabrutinib and fixed-duration therapy with venetoclax-obinutuzumab are effective for previously untreated chronic lymphocytic leukaemia. We hypothesised that frontline time-limited, minimal residual disease (MRD)-guided triplet therapy with acalabrutinib, venetoclax, and obinutuzumab would induce deep (ie, more patients with undetectable MRD) and durable remissions. Methods In this open-label, single-arm, investigator-sponsored, phase 2 study, patients with chronic lymphocytic leukaemia or small lymphocytic lymphoma were recruited from two academic hospitals in Boston, MA, USA. Eligible patients were aged 18 years or older, with an Eastern Cooperative Oncology Group performance status of 0-2, and were treatment naive. Patients were treated in 28 day cycles. Acalabrutinib monotherapy was given orally at 100 mg twice daily for cycle 1, then combined for six cycles with intravenous obinutuzumab (100 mg on cycle 2 day 1, 900 mg on day 2, 1000 mg on day 8, and 1000 mg on day 15 and on day 1 of cycles 3-7); and from the beginning of cycle 4, oral venetoclax was dosed daily using an accelerated ramp-up from 20 mg on day 1 to 400 mg by day 22 and continued at this dose thereafter. Patients continued on acalabrutinib 100 mg twice daily and venetoclax 400 mg once daily until day 1 of cycle 16 or day 1 of cycle 25. If the patient had undetectable MRD in the bone marrow they were given the option to discontinue therapy at the start of cycle 16 (if also in complete remission) or at the start of cycle 25 (if at least in partial remission). The primary endpoint was complete remission with undetectable MRD in the bone marrow (defined as