Centre Hospitalier Universitaire (CHU) de Reims, Hôpital Robert Debré, Reims, France.
Université Reims Champagne-Ardenne, Unité de Formation et de Recherche (UFR) Médecine, Reims, France.
Blood. 2019 Aug 15;134(7):641-644. doi: 10.1182/blood.2019000854. Epub 2019 Jun 26.
Mutational analyses performed following acquired ibrutinib resistance have suggested that chronic lymphocytic leukemia (CLL) progression on ibrutinib is linked to mutations in Bruton tyrosine kinase () and/or phospholipase Cγ2 () genes. Mutational information for patients still on ibrutinib is limited. We report a study aimed to provide a "snapshot" of the prevalence of mutations in a real-life CLL cohort still on ibrutinib after at least 3 years of treatment. Of 204 patients who initiated ibrutinib via an early-access program at 29 French Innovative Leukemia Organization (FILO) centers, 63 (31%) were still on ibrutinib after 3 years and 57 provided a fresh blood sample. Thirty patients had a CLL clone ≥0.5 × 10/L, enabling next-generation sequencing (NGS); and mutations were detected in 57% and 13% of the NGS samples, respectively. After median follow-up of 8.5 months from sample collection, the presence of a mutation was significantly associated with subsequent CLL progression ( = .0005 vs no mutation). Our findings support that mutational analysis should be considered in patients receiving ibrutinib who have residual clonal lymphocytosis, and that clinical trials are needed to evaluate whether patients with a mutation may benefit from an early switch to another treatment.
在获得依鲁替尼耐药后进行的突变分析表明，依鲁替尼治疗的慢性淋巴细胞白血病（CLL）进展与 Bruton 酪氨酸激酶（BTK）和/或磷脂酶 Cγ2（PLCγ2）基因突变有关。关于仍在接受依鲁替尼治疗的患者的突变信息有限。我们报告了一项研究，旨在提供仍在接受依鲁替尼治疗至少 3 年的真实 CLL 队列中突变的流行情况的“快照”。在 29 个法国创新白血病组织（FILO）中心通过早期准入计划开始接受依鲁替尼治疗的 204 名患者中，有 63 名（31%）在 3 年后仍在接受依鲁替尼治疗，其中 57 名提供了新鲜血液样本。30 名患者的 CLL 克隆≥0.5×10/L，可进行下一代测序（NGS）；在 30 个 NGS 样本中，分别检测到 57%和 13%的 和 突变。在从样本采集开始的中位随访 8.5 个月后，存在 突变与随后的 CLL 进展显著相关（=0.0005 vs 无 突变）。我们的发现支持在接受依鲁替尼治疗且仍有克隆性淋巴细胞增多的患者中应考虑进行突变分析，并且需要临床试验来评估是否存在 突变的患者可能从早期转换为另一种治疗中获益。
