Dr Tedeschi on Long-Term Data With First-Line Ibrutinib in CLL

Alessandra Tedeschi, MD, consultant, hematology, Department of Hematology, Niguarda Hospital, Milan, Italy, discusses 10-year follow-up data from the phase 3 RESONATE-2 trial (NCT01722487) investigating first-line ibrutinib (Imbruvica) in treatment-naive chronic lymphocytic leukemia (CLL).

The international, multicentre, open-label, trial compared ibrutinib monotherapy with chlorambucil in 269 patients with previously untreated CLL or small lymphocytic leukemia who were aged 65 years or older, Tedeschi begins.

Long-term follow-up data from the RESONATE-2 study were presented at the 2024 EHA Hybrid Congress and confirmed that ibrutinib produced and sustained improvements in progression-free survival (PFS) vs chlorambucil for patients with CLL in the first line, she reports. At a median follow-up of 10 years, the median PFS was 8.9 years in the ibrutinib arm vs 1.3 years in the chlorambucil arm (HR, 0.16; 95% CI, 0.11–0.22; P < 0.0001). PFS benefit was noted across all subgroups, including those with high-risk genomic features such as TP53 mutations, unmutated IGHV, or 11q deletions. In these high-risk groups, the HR was 0.09 (95% CI, 0.05–0.15; P < 0.0001), underscoring the broad applicability of ibrutinib in various patient populations.

The study also showed that the median overall survival (OS) had not been reached for patients treated with ibrutinib after up to 10 years of follow-up. At 9 years, the OS rate was 68% (95% CI, 58.6–75.7). Notably, 27% of patients remained on ibrutinib after 10 years, with a median duration of treatment of 6.2 years (range, 0.06-10.2). These findings illustrate the durability of response and the potential for long-term disease control with ibrutinib.

Regarding safety, long-term treatment with ibrutinib was well tolerated, with no new safety signals emerging over the course of the study, Tedeschi continues. The most significant adverse effects (AEs) occurred during the first year of treatment. In the later years of follow-up, the rates of AEs of interest were relatively low. During years 8 to 9 and 9 to 10, hypertension was reported in 28% (n=15) and 26% (n=11) of patients, respectively, while atrial fibrillation was reported in 8% (n=4) and 9% (n=4) of patients, respectively.

This study is particularly noteworthy as it represents the longest follow-up ever reported for a BTK inhibitor in treatment-naive CLL, Tedeschi emphasizes. The sustained efficacy and manageable safety profile of ibrutinib over a decade highlight its role as a cornerstone in the first-line treatment of CLL, especially for patients with high-risk genomic features.