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

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...

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Detalles Bibliográficos
Autores: Burger, Jan A|||0000-0002-6177-7572, Robak, Tadeusz|||0000-0002-3411-6357, Demirkan, Fatih|||0000-0002-1172-8668, Bairey, Osnat, Moreno, Carolina, Simpson, David, Munir, Talha|||0000-0002-2901-0769, Stevens, Don A., Dai, Sandra, Cheung, Leo W.K, Kwei, Kevin, Lal, Indu, Hsu, Emily, Kipps, Thomas J|||0000-0002-0064-4549, Tedeschi, Alessandra
Tipo de recurso: artículo
Fecha de publicación:2022
País:España
Institución:Universitat Autònoma de Barcelona
Repositorio:Dipòsit Digital de Documents de la UAB
Idioma:inglés
OAI Identifier:oai:ddd.uab.cat:277655
Acceso en línea:https://ddd.uab.cat/record/277655
https://dx.doi.org/urn:doi:10.1080/10428194.2021.2020779
Access Level:acceso abierto
Palabra clave:Chronic lymphocytic leukemia
Ibrutinib
Chlorambucil
Obinutuzumab
Pooled analysis
Descripción
Sumario: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).

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