The Ohio State University Comprehensive Cancer Center, Columbus, OH.
Alliance Statistics and Data Center, Mayo Clinic, Rochester, MN.
Blood. 2024 Apr 18;143(16):1616-1627. doi: 10.1182/blood.2023021959.
A041202 (NCT01886872) is a phase 3 study comparing bendamustine plus rituximab (BR) with ibrutinib and the combination of ibrutinib plus rituximab (IR) in previously untreated older patients with chronic lymphocytic leukemia (CLL). The initial results showed that ibrutinib-containing regimens had superior progression-free survival (PFS) and rituximab did not add additional benefits. Here we present an updated analysis. With a median follow-up of 55 months, the median PFS was 44 months (95% confidence interval [CI], 38-54) for BR and not yet reached in either ibrutinib-containing arm. The 48-month PFS estimates were 47%, 76%, and 76% for BR, ibrutinib, and IR, respectively. The benefit of ibrutinib regimens over chemoimmunotherapy was consistent across subgroups of patients defined by TP53 abnormalities, del(11q), complex karyotype, and immunoglobulin heavy chain variable region (IGHV). No significant interaction effects were observed between the treatment arm and del(11q), the complex karyotype, or IGHV. However, a greater difference in PFS was observed among the patients with TP53 abnormalities. There was no difference in the overall survival. Notable adverse events with ibrutinib included atrial fibrillation (afib) and hypertension. Afib was observed in 11 patients (pts) on BR (3%) and 67 pts on ibrutinib (18%). All-grade hypertension was observed in 95 pts on BR (27%) and 263 pts on ibrutinib (55%). These data show that ibrutinib regimens prolong PFS compared with BR for older patients with treatment-naïve CLL. These benefits were observed across subgroups, including high-risk groups. Strikingly, within the ibrutinib arms, there was no inferior PFS for patients with abnormalities in TP53, the highest risk feature observed in CLL. These data continue to demonstrate the efficacy of ibrutinib in treatment-naïve CLL.
A041202(NCT01886872)是一项比较苯达莫司汀联合利妥昔单抗(BR)与伊布替尼以及伊布替尼联合利妥昔单抗(IR)在初治老年慢性淋巴细胞白血病(CLL)患者中的疗效的 3 期研究。最初的结果显示,含伊布替尼的方案具有更好的无进展生存期(PFS),而利妥昔单抗并未带来额外的获益。在这里,我们提供了一项更新的分析。中位随访 55 个月时,BR 的中位 PFS 为 44 个月(95%置信区间[CI],38-54),而在伊布替尼组中均未达到。BR、伊布替尼和 IR 的 48 个月 PFS 估计值分别为 47%、76%和 76%。伊布替尼方案较化疗免疫治疗的获益在定义为 TP53 异常、del(11q)、复杂核型和免疫球蛋白重链可变区(IGHV)的患者亚组中是一致的。未观察到治疗组与 del(11q)、复杂核型或 IGHV 之间存在显著的交互作用。然而,在 TP53 异常的患者中,PFS 的差异更大。总生存无差异。伊布替尼的主要不良反应包括心房颤动(afib)和高血压。BR 组有 11 例(3%)和伊布替尼组有 67 例(18%)出现 afib。BR 组有 95 例(27%)和伊布替尼组有 263 例(55%)出现 1-2 级高血压。这些数据表明,与 BR 相比,伊布替尼方案可延长初治老年 CLL 患者的 PFS。这些获益在包括高危组在内的各亚组中均观察到。值得注意的是,在伊布替尼组中,TP53 异常患者的 PFS 并未降低,TP53 是 CLL 中观察到的最高危特征。这些数据继续证明了伊布替尼在初治 CLL 中的疗效。