Purpose: The phase II CAPTIVATE study investigated first-line treatment with ibrutinib plus venetoclax for chronic lymphocytic leukemia in two cohorts: minimal residual disease (MRD)-guided randomized treatment discontinuation (MRD cohort) and fixed duration (FD cohort). We report tumor debulking and tumor lysis syndrome (TLS) risk category reduction with three cycles of single-agent ibrutinib lead-in before initiation of venetoclax using pooled data from the MRD and FD cohorts. Patients and Methods: In both cohorts, patients initially received three cycles of ibrutinib 420 mg/day then 12 cycles of ibrutinib plus venetoclax (5-week ramp-up to 400 mg/day). Results: In the total population (N = 323), the following decreases from baseline to after ibrutinib lead-in were observed: percentage of patients with a lymph node diameter ≥5 cm decreased from 31% to 4%, with absolute lymphocyte count ≥25 × 109/L from 76% to 65%, with high tumor burden category for TLS risk from 23% to 2%, and with an indication for hospitalization (high TLS risk, or medium TLS risk and creatinine clearance <80 mL/minute) from 43% to 18%. Laboratory TLS per Howard criteria occurred in one patient; no clinical TLS was observed. Conclusions: Three cycles of ibrutinib lead-in before venetoclax initiation provides effective tumor debulking, decreases the TLS risk category and reduces the need for hospitalization for intensive monitoring for TLS.

中文翻译：

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在开始使用 Venetoclax 之前使用依鲁替尼进行有效的肿瘤减灭：来自 CAPTIVATE 最小残留疾病和固定持续时间队列的结果

目的：II 期 CAPTIVATE 研究在两个队列中调查了依鲁替尼加维奈托克治疗慢性淋巴细胞白血病的一线治疗：微小残留病 (MRD) 引导的随机治疗终止（MRD 队列）和固定疗程（FD 队列）。我们使用 MRD 和 FD 队列的汇总数据报告，在开始维奈托克之前，通过三个周期的单药依鲁替尼导入，可实现肿瘤减灭和肿瘤溶解综合征 (TLS) 风险类别降低。患者和方法：在两个队列中，患者最初接受 3 个周期的依鲁替尼 420 毫克/天，然后接受 12 个周期的依鲁替尼加维奈托克（5 周增加至 400 毫克/天）。结果：在总人群 (N = 323) 中，观察到从基线到伊布替尼导入后出现以下下降：淋巴结直径≥5 cm的患者比例从31%下降至4%，绝对淋巴细胞计数≥25×109/L的患者比例从76%下降至65%，TLS风险的高肿瘤负荷类别从23%下降至2% ，并且有住院指征(高TLS风险，或中等TLS风险和肌酐清除率＜80mL/分钟)从43％到18％。一名患者发生了符合霍华德标准的实验室 TLS；未观察到临床 TLS。结论：在开始维奈托克之前进行三个周期的依鲁替尼导入可有效减灭肿瘤，降低 TLS 风险类别，并减少住院进行 TLS 强化监测的需要。或中等 TLS 风险和肌酐清除率＜80 mL/分钟）从 43% 降至 18%。一名患者发生了符合霍华德标准的实验室 TLS；未观察到临床 TLS。结论：在开始维奈托克之前进行三个周期的依鲁替尼导入可有效减灭肿瘤，降低 TLS 风险类别，并减少住院进行 TLS 强化监测的需要。或中等 TLS 风险和肌酐清除率＜80 mL/分钟）从 43% 降至 18%。一名患者发生了符合霍华德标准的实验室 TLS；未观察到临床 TLS。结论：在开始维奈托克之前进行三个周期的依鲁替尼导入可有效减灭肿瘤，降低 TLS 风险类别，并减少住院进行 TLS 强化监测的需要。