Acalabrutinib is a selective irreversible Bruton tyrosine kinase (BTK) inhibitor that does not affect IL2-associated tyrosine kinase or antibody-dependent cellular cytotoxicity, making it an attractive candidate for combination therapy with anti-CD20 antibodies. We investigated acalabrutinib plus obinutuzumab in a phase Ib/II study (NCT02296918) of patients with treatment-naïve or relapsed/refractory chronic lymphocytic leukemia (CLL). Nineteen treatment-naïve and 26 relapsed/refractory patients were treated with acalabrutinib (100 mg twice daily) until progression and obinutuzumab (cycle 1: 100 mg day 1, 900 mg day 2, 1000 mg days 8 and 15; cycles 2-6: 1,000 mg day 1). Grade 3/4 adverse events occurred in 71% of patients. Overall response rates were 95% (treatment-naïve) and 92% (relapsed/refractory). Thirty-two percent of treatment-naïve and 8% of relapsed/refractory patients achieved complete remission. At 36 months, 94% (treatment-naïve) and 88% (relapsed/refractory) were progression free. Acalabrutinib plus obinutuzumab was well tolerated, producing high and durable responses in treatment-naïve and relapsed/refractory CLL. SIGNIFICANCE: Rituximab plus the less selective BTK inhibitor ibrutinib has not shown benefit in CLL; however, the selective BTK inhibitor acalabrutinib plus the antibody-dependent cellular cytotoxicity-enhanced antibody obinutuzumab yielded durable responses that deepened over time in treatment-naïve and relapsed/refractory CLL, supporting the evaluation of this approach in larger, comparative studies in CLL.This article is highlighted in the In This Issue feature, p. 327.

中文翻译：

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Acalabrutinib 加 Obinutuzumab 治疗初治和复发/难治性慢性淋巴细胞白血病。

Acalabrutinib 是一种选择性不可逆布鲁顿酪氨酸激酶 (BTK) 抑制剂，不影响 IL2 相关酪氨酸激酶或抗体依赖性细胞毒性，使其成为与抗 CD20 抗体联合治疗的有吸引力的候选药物。我们在一项针对初治或复发/难治性慢性淋巴细胞白血病 (CLL) 患者的 Ib/II 期研究 (NCT02296918) 中调查了 acalabrutinib 加 obinutuzumab。19 名初治患者和 26 名复发/难治性患者接受 acalabrutinib（100 mg，每天两次）直至疾病进展和 obinutuzumab（第 1 周期：第 1 天 100 mg、第 2 天 900 mg、第 8 天和第 15 天 1000 mg；第 2-6 周期： 1,000 毫克第 1 天）。71% 的患者发生 3/4 级不良事件。总体反应率为 95%（未接受过治疗）和 92%（复发/难治性）。32% 的初治患者和 8% 的复发/难治患者实现了完全缓解。在 36 个月时，94%（初治）和 88%（复发/难治）患者无进展。Acalabrutinib 加 obinutuzumab 耐受性良好，在初治和复发/难治性 CLL 中产生高且持久的反应。意义：利妥昔单抗加选择性较低的 BTK 抑制剂依鲁替尼未显示出对 CLL 的益处；然而，选择性 BTK 抑制剂 acalabrutinib 加上抗体依赖性细胞毒性增强抗体 obinutuzumab 产生了持久的反应，随着时间的推移在初治和复发/难治性 CLL 中加深，支持在更大的 CLL 比较研究中评估这种方法。文章在本期特刊中突出显示，p. 327.