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Leukemia. 2018 Jan;32(1):83-91. doi: 10.1038/leu.2017.175. Epub 2017 Jun 8.

Extended follow-up and impact of high-risk prognostic factors from the phase 3 RESONATE study in patients with previously treated CLL/SLL.

Author information

1
Dana-Farber Cancer Institute, Boston, MA, USA.
2
St James Institute of Oncology, Leeds, UK.
3
MD Anderson Cancer Center, Houston, TX, USA.
4
Hofstra Northwell School of Medicine, Hempstead, NY, USA.
5
Vanderbilt-Ingram Cancer Center, Nashville, TN, USA.
6
Stanford University School of Medicine, Stanford, CA, USA.
7
Peter MacCallum Cancer Centre and St Vincent's Hospital, Melbourne, Australia.
8
Royal North Shore Hospital, Sydney, Australia.
9
Medical University of Vienna, Vienna, Austria.
10
University of Rochester Cancer Center, Rochester, NY, USA.
11
Weill Cornell Medical College/New York Presbyterian Hospital, New York, NY, USA.
12
UCSD Moores Cancer Center, San Diego, CA, USA.
13
Hôpital Avicenne, Paris, France.
14
Beaumont Hospital, Dublin, Ireland.
15
Universita Vita-Salute San Raffaele, Milan, Italy.
16
Hospital Clinic, Barcelona, Spain.
17
Niguarda Cancer Center Niguarda Hospital, Milan, Italy.
18
David Geffen School of Medicine at UCLA, Los Angeles, CA, USA.
19
Hospital de la Santa Creu Sant Pau, Barcelona, Spain.
20
Swedish Cancer Institute, Seattle, WA, USA.
21
Pharmacyclics LLC, an AbbVie Company, Sunnyvale, CA, USA.
22
The Ohio State University Medical Center, Columbus, OH, USA.

Abstract

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.

PMID:
28592889
PMCID:
PMC5770586
DOI:
10.1038/leu.2017.175
[Indexed for MEDLINE]
Free PMC Article

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