Abstract

We conducted an observational study (FIRE) to understand the effectiveness and safety outcomes of ibrutinib in patients with chronic lymphocytic leukemia (CLL) in France, after a maximum follow-up of five years. Patients were included according to the French marketing authorization in 2016 (i.e. patients with relapsed or refractory CLL or to previously untreated CLL patients with deletion 17p and/or tumor protein p53 mutations unsuitable for chemoimmunotherapy) and could have initiated ibrutinib more than 30 days prior their enrolment in the study (i.e. retrospective patients) or between 30 days before and 14 days after their enrolment (i.e. prospective patients). The results showed that in the effectiveness population (N = 388), the median progression-free survival (PFS) was 53.1 (95% CI: 44.5–60.5) months for retrospective patients and 52.9 (95% CI: 40.3–60.6) months for prospective patients and no difference was shown between the PFS of patients who had at least one dose reduction versus the PFS of patients without dose reduction (p = 0.7971 for retrospective and p = 0.3163 for prospective patients). For both retrospective and prospective patients, the median overall survival was not reached. The most frequent treatment-emergent adverse event of interest was infections (57.6% retrospective; 71.4% prospective). A total of 14.6% of the retrospective patients and 22.4% of the prospective patients had an adverse event leading to death. Our findings on effectiveness were consistent with other studies and the fact that patients with dose reductions had similar PFS than patients without dose reduction is reassuring. No additional safety concerns than those already mentioned in previous studies could be noticed.

Trial registration ClinicalTrials.gov, NCT03425591. Registered 1 February 2018 – Retrospectively registered.

中文翻译：

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非介入性 FIRE 研究中依鲁替尼治疗慢性淋巴细胞白血病患者的有效性和安全性的最终结果

摘要

我们进行了一项观察性研究 (FIRE)，旨在了解依鲁替尼在法国慢性淋巴细胞白血病 (CLL) 患者中的有效性和安全性结果，经过最长五年的随访。根据 2016 年法国上市授权，患者被纳入（即患有复发或难治性 CLL 的患者或先前未经治疗的具有 17p 缺失和/或肿瘤蛋白 p53 突变且不适合化学免疫治疗的 CLL 患者），并且可能在治疗前 30 天以上开始使用依鲁替尼。入组研究（即回顾性患者）或入组前 30 天至入组后 14 天（即前瞻性患者）。结果显示，在有效人群（N  = 388）中，回顾性患者的中位无进展生存期（PFS）为 53.1（95% CI：44.5-60.5）个月，而中位无进展生存期（PFS）为 52.9（95% CI：40.3-60.6）个月。对于前瞻性患者，至少进行一次剂量减少的患者的 PFS 与未减少剂量的患者的 PFS 之间没有显示差异（ 回顾性p = 0.7971， 前瞻性患者p = 0.3163）。对于回顾性和前瞻性患者，均未达到中位总生存期。最常见的治疗相关不良事件是感染（回顾性发生率为 57.6%；前瞻性发生率为 71.4%）。共有 14.6% 的回顾性患者和 22.4% 的前瞻性患者发生了导致死亡的不良事件。我们的有效性研究结果与其他研究一致，并且减少剂量的患者与未减少剂量的患者具有相似的 PFS，这一事实令人放心。除了之前的研究中已经提到的安全问题外，没有发现其他安全问题。

试验注册 ClinicalTrials.gov，NCT03425591。2018 年 2 月 1 日注册 – 追溯注册。