Memorial Sloan Kettering Cancer Center, New York.
BeiGene, Ltd., Emeryville.
Haematologica. 2022 Nov 1;107(11):2630-2640. doi: 10.3324/haematol.2021.280376.
Among patients with chronic lymphocytic leukemia (CLL) with deletion 17p (del[17p]), evidence from clinical trials for the effectiveness of single-agent ibrutinib as first-line therapy is limited. This retrospective analysis compared real-world clinical outcomes among patients with CLL, with and without del(17p), treated with first-line ibrutinib monotherapy. Overall survival, time to next treatment, time to treatment discontinuation, and reasons for ibrutinib discontinuation were evaluated. Using data from a real-world database, patients included were aged ≥18 years, had been diagnosed with CLL between January 1, 2011 and December 31, 2019, had undergone cytogenetic testing, and had received first-line ibrutinib monotherapy. A total of 1,069 patients were included in the analysis (62.7% male; median age 69 years); 23.8% (n=254) had del(17p). The median overall survival was significantly shorter in patients with del(17p) than in patients without (57.7 months vs. not reached; P=0.0006). Similar results were observed for median time to next treatment (49.4 months vs. not reached, P=0.0330). The median time to treatment discontinuation was non-significantly shorter in the group of patients with del(17p) (32.5 months vs. 42.9 months, P=0.3370). Results of an adjusted Cox proportional hazards model showed that the group with del(17p) was at significantly higher risk of death than was the group without del(17p) (hazard ratio=1.70, P=0.0031). Event rates for switching to new treatment and discontinuation were higher but not statistically significantly so. The most common reason for discontinuing ibrutinib treatment in both groups was toxicity, but discontinuation due to progression was significantly more frequent among patients with del(17p) (20% vs. 6%; P<0.0001). This study identifies an unmet need for more effective first-line therapeutic options in patients with CLL/small lymphocytic lymphoma and del(17p), despite the advent of ibrutinib.
在患有 17p 缺失（del[17p]）的慢性淋巴细胞白血病（CLL）患者中，临床试验证明单药伊布替尼作为一线治疗的有效性证据有限。这项回顾性分析比较了接受一线伊布替尼单药治疗的 CLL 患者和无 del(17p)患者的真实世界临床结局。评估了总生存期、下一次治疗时间、治疗终止时间和伊布替尼停药原因。使用真实世界数据库中的数据，纳入的患者年龄≥18 岁，在 2011 年 1 月 1 日至 2019 年 12 月 31 日期间被诊断为 CLL，进行了细胞遗传学检测，并接受了一线伊布替尼单药治疗。共纳入 1069 例患者进行分析（62.7%为男性；中位年龄 69 岁）；23.8%（n=254）存在 del(17p)。del(17p)患者的中位总生存期明显短于无 del(17p)患者（57.7 个月 vs. 未达到；P=0.0006）。下一次治疗时间的中位结果也相似（49.4 个月 vs. 未达到，P=0.0330）。del(17p)组的中位治疗终止时间明显缩短（32.5 个月 vs. 42.9 个月，P=0.3370）。调整后的 Cox 比例风险模型结果显示，del(17p)组死亡风险明显高于无 del(17p)组（风险比=1.70，P=0.0031）。两组新治疗和停药的事件发生率较高，但无统计学意义。两组停止伊布替尼治疗的最常见原因是毒性，但 del(17p)组因进展而停药的比例明显更高（20% vs. 6%；P<0.0001）。这项研究表明，尽管伊布替尼已经问世，但对于存在 17p 缺失的 CLL/小淋巴细胞淋巴瘤患者，仍需要更有效的一线治疗方案。
