TY - JOUR
T1 - Long-term efficacy and safety of first-line ibrutinib treatment for patients with CLL/SLL
T2 - 5 years of follow-up from the phase 3 RESONATE-2 study
AU - Burger, Jan A.
AU - Barr, Paul M.
AU - Robak, Tadeusz
AU - Owen, Carolyn
AU - Ghia, Paolo
AU - Tedeschi, Alessandra
AU - Bairey, Osnat
AU - Hillmen, Peter
AU - Coutre, Steven E.
AU - Devereux, Stephen
AU - Grosicki, Sebastian
AU - McCarthy, Helen
AU - Simpson, David
AU - Offner, Fritz
AU - Moreno, Carol
AU - Dai, Sandra
AU - Lal, Indu
AU - Dean, James P.
AU - Kipps, Thomas J.
N1 - Funding Information:
Conflict of interest JAB reported honoraria and a consulting/advisory role with Janssen; speakers’ bureau and travel expenses from Gilead, Janssen, Novartis, Pharmacyclics LLC, an AbbVie Company, and TG Therapeutics; and research funding from BeiGene, Gilead, Pharma-cyclics LLC, an AbbVie Company, and TG Therapeutics. PMB reported a consultancy/advisory role for AbbVie and Pharmacyclics LLC, an AbbVie Company; and research funding from Pharmacyclics LLC, an AbbVie Company. TR reported research funding from Pharmacyclics LLC, an AbbVie company. CO reported honoraria from Gilead, Janssen, AbbVie, Roche, Merck, Teva, and AstraZeneca. PG reported honoraria from AbbVie, Acerta, BeiGene, Gilead, Roche, Sunesis, Celgene, and Janssen; a consultancy/advisory role from AbbVie, Acerta, BeiGene, Gilead, Janssen, Pharmacyclics LLC, an AbbVie Company, Celgene, and Sunesis; speakers’ bureau for Gilead; and research funding from AbbVie, Gilead, Janssen, and Novartis. AT reported a consultancy/advisory role for Janssen spa, Gilead, Sunesis, and AbbVie; and speakers’ bureau for Janssen. OB reported a consultancy/advisory role for AbbVie and research funding from Janssen. PH reported honoraria, a consultancy/advisory role, and research funding from Janssen, Pharmacyclics LLC, an AbbVie Company, and AbbVie; and travel expenses from Janssen and AbbVie. SEC reported honoraria from Pharmacyclics LLC, an AbbVie Company, and Jans-sen; a consultancy/advisory role for AbbVie, Astellas, AstraZeneca, Celgene, Genentech, Pharmacyclics LLC, an AbbVie Company, Novartis, and Janssen; travel, accommodations, expenses from Abb-Vie, BeiGene, Celgene, Genentech, Janssen, Pharmacyclics LLC, an AbbVie Company; expert testimony for Genentech; other relationship with BeiGene; and research funding from Celgene, Gilead, Janssen, Pharmacyclics LLC, an AbbVie Company, AbbVie, Takeda, and Acerta. SD reported a consultancy/advisory role for AbbVie, Janssen, GlaxoSmithKline, and Bristol-Myers Squibb; and speakers’ bureau and travel expenses for Janssen and Gilead. HM reported honoraria and travel expenses from AbbVie, Janssen, Novartis, and Roche; and a consultancy/advisory role with Janssen. DS reported honoraria from Celgene, Roche, MSD, and Janssen; travel expenses from Celgene, Bristol-Myers Squibb, Janssen, and Novartis; and research funding from Amgen, MSD, Pharmacyclics LLC, an AbbVie Company, AbbVie, Sanofi, Roche, BeiGene, and Acerta. CM reported a consulting/advisory role with Pharmacyclics LLC, an AbbVie Company, Janssen, and AbbVie. SD reported employment with Pharmacyclics LLC, an AbbVie Company; and stock ownership with AbbVie, Cel-gene, Gilead, GSK, and Exelixis. IL reported employment with Pharmacyclics, an AbbVie Company, and spouse employment with The Permanente Medical Group; and stock ownership with AbbVie, Gilead Sciences, Clovis, Infinity, The Permanente Medical Group, and Reviva Pharmaceuticals. JPD reported employment with Pharma-cyclics LLC, an AbbVie Company, and CTI BioPharma Corp; and stock ownership with AbbVie and CTI BioPharma Corp. TJK reported a consultancy/advisory role for AbbVie, Genentech-Roche, Gilead, Pharmacyclics LLC, an AbbVie Company, and Celgene; and research funding from AbbVie, Genentech-Roche, Pharmacyclics LLC, an AbbVie Company, and Oncternal. SG and FO reported no relevant financial disclosures.
Funding Information:
Acknowledgments We thank the patients who participated in the study and their supportive families, as well as the investigators and clinical research staff from the study centers. This study was sponsored by Pharmacyclics LLC, an AbbVie Company. Medical writing support was provided by Valerie Hilliard, PhD, and funded by Pharmacyclics LLC, an AbbVie Company.
Publisher Copyright:
© 2019, The Author(s).
PY - 2020/3/1
Y1 - 2020/3/1
N2 - RESONATE-2 is a phase 3 study of first-line ibrutinib versus chlorambucil in chronic lymphocytic leukemia (CLL)/small lymphocytic lymphoma (SLL). Patients aged ≥65 years (n = 269) were randomized 1:1 to once-daily ibrutinib 420 mg continuously or chlorambucil 0.5–0.8 mg/kg for ≤12 cycles. With a median (range) follow-up of 60 months (0.1–66), progression-free survival (PFS) and overall survival (OS) benefits for ibrutinib versus chlorambucil were sustained (PFS estimates at 5 years: 70% vs 12%; HR [95% CI]: 0.146 [0.098–0.218]; OS estimates at 5 years: 83% vs 68%; HR [95% CI]: 0.450 [0.266–0.761]). Ibrutinib benefit was also consistent in patients with high prognostic risk (TP53 mutation, 11q deletion, and/or unmutated IGHV) (PFS: HR [95% CI]: 0.083 [0.047–0.145]; OS: HR [95% CI]: 0.366 [0.181–0.736]). Investigator-assessed overall response rate was 92% with ibrutinib (complete response, 30%; 11% at primary analysis). Common grade ≥3 adverse events (AEs) included neutropenia (13%), pneumonia (12%), hypertension (8%), anemia (7%), and hyponatremia (6%); occurrence of most events as well as discontinuations due to AEs decreased over time. Fifty-eight percent of patients continue to receive ibrutinib. Single-agent ibrutinib demonstrated sustained PFS and OS benefit versus chlorambucil and increased depth of response over time.
AB - RESONATE-2 is a phase 3 study of first-line ibrutinib versus chlorambucil in chronic lymphocytic leukemia (CLL)/small lymphocytic lymphoma (SLL). Patients aged ≥65 years (n = 269) were randomized 1:1 to once-daily ibrutinib 420 mg continuously or chlorambucil 0.5–0.8 mg/kg for ≤12 cycles. With a median (range) follow-up of 60 months (0.1–66), progression-free survival (PFS) and overall survival (OS) benefits for ibrutinib versus chlorambucil were sustained (PFS estimates at 5 years: 70% vs 12%; HR [95% CI]: 0.146 [0.098–0.218]; OS estimates at 5 years: 83% vs 68%; HR [95% CI]: 0.450 [0.266–0.761]). Ibrutinib benefit was also consistent in patients with high prognostic risk (TP53 mutation, 11q deletion, and/or unmutated IGHV) (PFS: HR [95% CI]: 0.083 [0.047–0.145]; OS: HR [95% CI]: 0.366 [0.181–0.736]). Investigator-assessed overall response rate was 92% with ibrutinib (complete response, 30%; 11% at primary analysis). Common grade ≥3 adverse events (AEs) included neutropenia (13%), pneumonia (12%), hypertension (8%), anemia (7%), and hyponatremia (6%); occurrence of most events as well as discontinuations due to AEs decreased over time. Fifty-eight percent of patients continue to receive ibrutinib. Single-agent ibrutinib demonstrated sustained PFS and OS benefit versus chlorambucil and increased depth of response over time.
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U2 - 10.1038/s41375-019-0602-x
DO - 10.1038/s41375-019-0602-x
M3 - Article
C2 - 31628428
AN - SCOPUS:85074797641
SN - 0887-6924
VL - 34
SP - 787
EP - 798
JO - Leukemia
JF - Leukemia
IS - 3
ER -