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Extended follow-up and impact of high-risk prognostic factors from the phase 3 RESONATE study in patients with previously treated CLL/SLL
In the phase 3 RESONATE study, ibrutinib demonstrated superior progression-free survival (PFS), overall survival (OS) and overall response rate (ORR) compared with ofatumumab in relapsed/refractory CLL patients with high-risk prognostic factors. We report updated results from RESONATE in these tradi...
Autores principales: | , , , , , , , , , , , , , , , , , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Nature Publishing Group
2018
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5770586/ https://www.ncbi.nlm.nih.gov/pubmed/28592889 http://dx.doi.org/10.1038/leu.2017.175 |
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author | Brown, J R Hillmen, P O’Brien, S Barrientos, J C Reddy, N M Coutre, S E Tam, C S Mulligan, S P Jaeger, U Barr, P M Furman, R R Kipps, T J Cymbalista, F Thornton, P Caligaris-Cappio, F Delgado, J Montillo, M DeVos, S Moreno, C Pagel, J M Munir, T Burger, J A Chung, D Lin, J Gau, L Chang, B Cole, G Hsu, E James, D F Byrd, J C |
author_facet | Brown, J R Hillmen, P O’Brien, S Barrientos, J C Reddy, N M Coutre, S E Tam, C S Mulligan, S P Jaeger, U Barr, P M Furman, R R Kipps, T J Cymbalista, F Thornton, P Caligaris-Cappio, F Delgado, J Montillo, M DeVos, S Moreno, C Pagel, J M Munir, T Burger, J A Chung, D Lin, J Gau, L Chang, B Cole, G Hsu, E James, D F Byrd, J C |
author_sort | Brown, J R |
collection | PubMed |
description | In the phase 3 RESONATE study, ibrutinib demonstrated superior progression-free survival (PFS), overall survival (OS) and overall response rate (ORR) compared with ofatumumab in relapsed/refractory CLL patients with high-risk prognostic factors. We report updated results from RESONATE in these traditionally chemotherapy resistant high-risk genomic subgroups at a median follow-up of 19 months. Mutations were detected by Foundation One Heme Panel. Baseline mutations in the ibrutinib arm included TP53 (51%), SF3B1 (31%), NOTCH1 (28%), ATM (19%) and BIRC3 (14%). Median PFS was not reached, with 74% of patients randomized to ibrutinib alive and progression-free at 24 months. The improved efficacy of ibrutinib vs ofatumumab continues in all prognostic subgroups including del17p and del11q. No significant difference within the ibrutinib arm was observed for PFS across most genomic subtypes, although a subset carrying both TP53 mutation and del17p had reduced PFS compared with patients with neither abnormality. Reduced PFS or OS was not evident in patients with only del17p. PFS was significantly better for ibrutinib-treated patients in second-line vs later lines of therapy. The robust clinical activity of ibrutinib continues to show ongoing efficacy and acceptable safety consistent with prior reports, independent of various known high-risk mutations. |
format | Online Article Text |
id | pubmed-5770586 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2018 |
publisher | Nature Publishing Group |
record_format | MEDLINE/PubMed |
spelling | pubmed-57705862018-01-22 Extended follow-up and impact of high-risk prognostic factors from the phase 3 RESONATE study in patients with previously treated CLL/SLL Brown, J R Hillmen, P O’Brien, S Barrientos, J C Reddy, N M Coutre, S E Tam, C S Mulligan, S P Jaeger, U Barr, P M Furman, R R Kipps, T J Cymbalista, F Thornton, P Caligaris-Cappio, F Delgado, J Montillo, M DeVos, S Moreno, C Pagel, J M Munir, T Burger, J A Chung, D Lin, J Gau, L Chang, B Cole, G Hsu, E James, D F Byrd, J C Leukemia Original Article In the phase 3 RESONATE study, ibrutinib demonstrated superior progression-free survival (PFS), overall survival (OS) and overall response rate (ORR) compared with ofatumumab in relapsed/refractory CLL patients with high-risk prognostic factors. We report updated results from RESONATE in these traditionally chemotherapy resistant high-risk genomic subgroups at a median follow-up of 19 months. Mutations were detected by Foundation One Heme Panel. Baseline mutations in the ibrutinib arm included TP53 (51%), SF3B1 (31%), NOTCH1 (28%), ATM (19%) and BIRC3 (14%). Median PFS was not reached, with 74% of patients randomized to ibrutinib alive and progression-free at 24 months. The improved efficacy of ibrutinib vs ofatumumab continues in all prognostic subgroups including del17p and del11q. No significant difference within the ibrutinib arm was observed for PFS across most genomic subtypes, although a subset carrying both TP53 mutation and del17p had reduced PFS compared with patients with neither abnormality. Reduced PFS or OS was not evident in patients with only del17p. PFS was significantly better for ibrutinib-treated patients in second-line vs later lines of therapy. The robust clinical activity of ibrutinib continues to show ongoing efficacy and acceptable safety consistent with prior reports, independent of various known high-risk mutations. Nature Publishing Group 2018-01 2017-07-21 /pmc/articles/PMC5770586/ /pubmed/28592889 http://dx.doi.org/10.1038/leu.2017.175 Text en Copyright © 2018 The Author(s) http://creativecommons.org/licenses/by-nc-nd/4.0/ This work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivs 4.0 International License. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license, users will need to obtain permission from the license holder to reproduce the material. To view a copy of this license, visit http://creativecommons.org/licenses/by-nc-nd/4.0/ |
spellingShingle | Original Article Brown, J R Hillmen, P O’Brien, S Barrientos, J C Reddy, N M Coutre, S E Tam, C S Mulligan, S P Jaeger, U Barr, P M Furman, R R Kipps, T J Cymbalista, F Thornton, P Caligaris-Cappio, F Delgado, J Montillo, M DeVos, S Moreno, C Pagel, J M Munir, T Burger, J A Chung, D Lin, J Gau, L Chang, B Cole, G Hsu, E James, D F Byrd, J C Extended follow-up and impact of high-risk prognostic factors from the phase 3 RESONATE study in patients with previously treated CLL/SLL |
title | Extended follow-up and impact of high-risk prognostic factors from the phase 3 RESONATE study in patients with previously treated CLL/SLL |
title_full | Extended follow-up and impact of high-risk prognostic factors from the phase 3 RESONATE study in patients with previously treated CLL/SLL |
title_fullStr | Extended follow-up and impact of high-risk prognostic factors from the phase 3 RESONATE study in patients with previously treated CLL/SLL |
title_full_unstemmed | Extended follow-up and impact of high-risk prognostic factors from the phase 3 RESONATE study in patients with previously treated CLL/SLL |
title_short | Extended follow-up and impact of high-risk prognostic factors from the phase 3 RESONATE study in patients with previously treated CLL/SLL |
title_sort | extended follow-up and impact of high-risk prognostic factors from the phase 3 resonate study in patients with previously treated cll/sll |
topic | Original Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5770586/ https://www.ncbi.nlm.nih.gov/pubmed/28592889 http://dx.doi.org/10.1038/leu.2017.175 |
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