Department of Leukemia, University of Texas MD Anderson Cancer Center, Houston, TX, USA.
Medical University of Lodz, Copernicus Memorial Hospital, Lodz, Poland.
Leuk Lymphoma. 2022 Jun;63(6):1375-1386. doi: 10.1080/10428194.2021.2020779. Epub 2022 Jan 11.
Genomic abnormalities, including del(17p)/ mutation, del(11q), unmutated IGHV, and mutations in , , , and predict poor outcomes with chemoimmunotherapy in chronic lymphocytic leukemia. To better understand the impact of these high-risk genomic features on outcomes with first-line ibrutinib-based therapy, we performed pooled analysis of two phase 3 studies with 498 patients randomized to receive ibrutinib- or chlorambucil-based therapy with median follow-up of 49.1 months. Ibrutinib-based therapy improved overall response rates (ORRs), complete response rates, and progression-free survival (PFS) versus chlorambucil-based therapy across all subgroups. In ibrutinib-randomized patients with versus without specified genomic features, ORR and PFS were comparable across subgroups. PFS hazard ratio (95% CI) for del(17p)/ mutated/ mutated: 1.05 (0.54-2.04); del(17p)/ mutation, del(11q), and/or unmutated IGHV: 1.11 (0.69-1.77); unmutated IGHV: 1.79 (0.99-3.24); and mutated 1.05 (0.65-1.69). This integrated analysis demonstrated efficacy of first-line ibrutinib-based treatment irrespective of cytogenetic and mutational risk features.Registered at ClinicalTrials.gov (NCT01722487 and NCT02264574).
基因组异常，包括 del(17p)/突变、del(11q)、未突变的 IGHV 以及 和 中的突变，与慢性淋巴细胞白血病的化疗免疫治疗不良预后相关。为了更好地了解这些高风险基因组特征对一线伊布替尼为基础的治疗结果的影响，我们对两项纳入 498 例患者的 3 期研究进行了汇总分析，这些患者被随机分配接受伊布替尼或苯丁酸氮芥为基础的治疗，中位随访时间为 49.1 个月。与苯丁酸氮芥为基础的治疗相比，伊布替尼为基础的治疗改善了所有亚组的总缓解率（ORR）、完全缓解率和无进展生存期（PFS）。在伊布替尼治疗的患者中，无论是否存在特定的基因组特征，ORR 和 PFS 在各亚组之间是可比的。伊布替尼治疗的 PFS 风险比（95%CI）为 del(17p)/突变/突变：1.05（0.54-2.04）；del(17p)/突变、del(11q)和/或未突变的 IGHV：1.11（0.69-1.77）；未突变的 IGHV：1.79（0.99-3.24）；和 突变：1.05（0.65-1.69）。这项综合分析表明，一线伊布替尼为基础的治疗具有疗效，与细胞遗传学和突变风险特征无关。在 ClinicalTrials.gov 注册（NCT01722487 和 NCT02264574）。
