Faculty, Staff and Student Publications
Language
English
Publication Date
10-30-2025
Journal
Blood
DOI
10.1182/blood.2024028205
PMID
40737596
PMCID
PMC12824676
PubMedCentral® Posted Date
8-5-2025
PubMedCentral® Full Text Version
Post-print
Abstract
With up to 10 years of follow-up, we report results from the final analysis of RESONATE- 2, a phase 3 study of first-line ibrutinib vs chlorambucil for the treatment of chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL). Patients aged ≥65 years with previously untreated CLL/SLL without del(17p) were randomly assigned to receive either single-agent ibrutinib (420 mg/d; n = 136) or chlorambucil (0.5-0.8 mg/kg; ≤12 cycles; n = 133). With a median follow-up of 9.6 years in the ibrutinib arm, the median progression-free survival (PFS) was 8.9 years (95% confidence interval [CI], 7.0 to not estimable [NE]) vs 1.3 years (95% CI, 0.9-1.6) for the chlorambucil arm. Among patients with unmutated immunoglobulin heavy chain variable (uIGHV), del (11q), mutated TP53, or complex karyotype, the median PFS was 8.4 years (95% CI, 6.8 to NE) with ibrutinib and 0.7 years (95% CI, 0.4-1.2) with chlorambucil. Median overall survival (OS) with ibrutinib was not reached. The most common adverse events (AEs) of any grade included diarrhea (52%), fatigue (41%), cough (39%), nausea (32%), arthralgia (31%), peripheral edema (31%), and hypertension (30%). During the entire study period, 34 of 136 patients (25%) had an ibrutinib dose reduction due to AEs; these AEs improved in 30 of 34 patients (88%). At study completion, 27% of patients remained on first-line ibrutinib treatment. This landmark RESONATE-2 study defines median PFS and demonstrates continued OS benefit of first-line ibrutinib treatment for patients with CLL/SLL, including those with high-risk genomic features. Sustained efficacy and tolerability of ibrutinib reemphasize the favorable benefit-risk profile. This trial was registered at www.ClinicalTrials.gov as NCT01722487/NCT01724346.
Keywords
Humans, Piperidines, Adenine, Leukemia, Lymphocytic, Chronic, B-Cell, Aged, Male, Female, Follow-Up Studies, Pyrimidines, Aged, 80 and over, Chlorambucil, Pyrazoles
Published Open-Access
yes
Recommended Citation
Burger, Jan A; Barr, Paul M; Robak, Tadeusz; et al., "Final Analysis of the Resonate-2 Study: Up to 10 Years of Follow-Up of First-Line Ibrutinib Treatment for CLL/SLL" (2025). Faculty, Staff and Student Publications. 5397.
https://digitalcommons.library.tmc.edu/uthgsbs_docs/5397
Graphical Abstract
Included in
Bioinformatics Commons, Biomedical Informatics Commons, Genetic Phenomena Commons, Medical Genetics Commons, Oncology Commons