2026-04-13T07:11:36Zhttps://recercat.cat/oai/request

oai:recercat.cat:2072/4688142025-06-12T10:43:42Zcom_2072_98col_2072_378192

00925njm 22002777a 4500 dc Burger, Jan A author Robak, Tadeusz author Demirkan, Fatih author Bairey, Osnat author Moreno, Carolina author Simpson, David author Munir, Talha author Stevens, Don A. author Dai, Sandra author Cheung, Leo W.K author Kwei, Kevin author Lal, Indu author Hsu, Emily author Kipps, Thomas J author Tedeschi, Alessandra author 2022 Altres ajuts: Pharmacyclics LLC; AbbVie Company. Genomic abnormalities, including del(17p)/TP53 mutation, del(11q), unmutated IGHV, and mutations in BIRC3, NOTCH1, SF3B1, and XPO1 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)/TP53 mutated/BIRC3 mutated: 1.05 (0.54-2.04); del(17p)/TP53 mutation, del(11q), and/or unmutated IGHV: 1.11 (0.69-1.77); unmutated IGHV: 1.79 (0.99-3.24); and NOTCH1 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). Chronic lymphocytic leukemia Ibrutinib Chlorambucil Obinutuzumab Pooled analysis Up to 6.5 years (median 4 years) of follow-up of first-line ibrutinib in patients with chronic lymphocytic leukemia/small lymphocytic lymphoma and high-risk genomic features : integrated analysis of two phase 3 studies