Final analysis of the RESONATE-2 study: up to 10 years of follow-up of first-line ibrutinib treatment for CLL/SLL.

Burger, JA.; Barr, PM.; Robak, T.; Owen, C.; Tedeschi, A.; Sarma, A.; Patten, PEM.; Grosicki, S.; McCarthy, H.; Offner, F.; Szafer-Glusman, E.; Zhou, C.; Szoke, A.; Neumayr, L.; Dean, JP.; Ghia, P.; Kipps, TJ.

Final analysis of the RESONATE-2 study: up to 10 years of follow-up of first-line ibrutinib treatment for CLL/SLL.

All Authors

Burger, JA.

Barr, PM.

Robak, T.

Owen, C.

Tedeschi, A.

Sarma, A.

Patten, PEM.

Grosicki, S.

McCarthy, H.

Offner, F.

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LTHT Author

Sarma, Anita

LTHT Department

Oncology
Haematology

Publication Date

2025

Item Type

Journal Article
Randomised Controlled Trial
Clinical Trial
Multicenter Study

Abstract

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.