Imbruvica Demonstrates Long-Term Efficacy, Safety in First-Line Treatment of Chronic Lymphocytic Leukemia

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Results from the Phase III RESONATE-2 trial found that Janssen-Cilag International NV’s Imbruvica (ibrutinib) demonstrated a higher level of median progression-free survival (PFS) in the first-line treatment of chronic lymphocytic leukemia (CLL) compared to chlorambucil. The data, presented at this year’s the European Hematology Association (EHA) Congress, found that with up to 10 years of follow-up, Imbruvica had a significantly longer median progression-free survival (PFS) of 8.9 years compared to 1.3 years for chlorambucil.¹

“When ibrutinib was first introduced more than ten years ago, it changed the course of (CLL) treatment, and today it remains a central part of the standard of care for patients living with B-cell malignancies,” said Alessandra Tedeschi, MD, Niguarda Hospital, Milan, Italy, clinical study investigator, in a press release. “The final analysis of the RESONATE-2 study confirms the favorable benefit-risk profile of ibrutinib is sustained over time, with the longest-follow up data of any targeted therapy in CLL and demonstrates its potential to enable patients diagnosed with CLL today to look forward to the possibility of a normalized life expectancy.”

The international, multicenter, open-label, randomized trial compared first-line ibrutinib monotherapy with chlorambucil in 269 previously untreated CLL patients aged 65 years and older without del(17p), who were randomly assigned to receive either 420 mg of daily oral ibrutinib monotherapy until disease progression or unacceptable toxicity or 12 cycles of intravenous chlorambucil, including 10 years of follow-up. The primary endpoint of the study was complete PFS, with secondary endpoints that included overall survival (OS), overall response rate (ORR), and safety.

Results found that the median OS had not been reached in the ibrutinib group and at 9 years, the OS rate was 68%. Additionally, 27% of patients treated with ibrutinib remained on therapy after the 10-year follow-up, with the median treatment duration averaging 6.2 years. Notably, the PFS benefit was reported to be considerably stronger for patients treated with ibrutinib in all subgroups, including those with high-risk genomic features—TP53 mutation, unmutated IGHV or 11q deletion (HR, 0.09; 95 percent CI, 0.05–0.15; p<0.0001).

Ibrutinib was generally well tolerated, as no new safety concerns were reported. At years 8-9 and 9-10, adverse events (AEs) were found to be 28% and 26% for hypertension, respectively, with 8% and 9% for atrial fibrillation, respectively. Further, 25% of patients required dose reductions due to AEs, with most resolving (28 of 34 patients), and 33% of patients stopped treatment due to AEs throughout the study, with 13% between year 8-9, and 7% during year 9-10.

Additionally, data compiled from RESONATE-2 and two other Phase III studies (ECOG1912 and iLLUMINATE) show that OS for ibrutinib-treated patients was comparable to the age-matched general European population.¹

“These findings suggest that treatment with ibrutinib, with or without the addition of a CD20 antibody, offers patients in Europe with chronic lymphocytic leukemia the potential of a standard life expectancy, comparable to that of their peers,” said Edmond Chan, MBChB, MD (Res), EMEA Therapeutic Area Lead Hematology, Johnson & Johnson Innovative Medicine, in the press release. “Our goal has been to change what a blood cancer diagnosis means, and with ibrutinib, we are proud to be at the forefront of leading where medicine is going.”

An additional poster presentation showcased real-world evidence in 286 patients to compare ibrutinib and acalabrutinib in real-world settings, with the goal of determining reduction strategies. A total of 171 patients started first-line treatment with acalabrutinib.

Results suggested that dose reductions in ibrutinib maintained efficacy and could effectively manage tolerability, with the median duration of first-line therapy of 21.3 months for the ibrutinib dose-reduction group and 11.1 months for the acalabrutinib group. Median duration of treatment was not reached for the ibrutinib group but was 9.5 months for the acalabrutinib group. Discontinuation rates were 37% for ibrutinib dose-reduction and 35% for acalabrutinib.¹

“These latest findings add to the robust data supporting ibrutinib, the most comprehensively studied Bruton’s tyrosine kinase inhibitor in the world, and the foundation of care in chronic lymphocytic leukemia,” said Mark Wildgust, PhD, VP, global medical affairs, oncology, Johnson & Johnson Innovative Medicine, in the press release. “As we reflect on a decade since its first approval, ibrutinib stands as a testament to progress that has redefined what it means to live with B-cell malignancies.”

Reference

1. Findings from landmark RESONATE-2 study confirm sustained survival benefit of IMBRUVICA® (ibrutinib) for first-line chronic lymphocytic leukaemia treatment with up to 10 years follow-up. Johnson & Johnson. June 14, 2024. Accessed June 14, 2024. https://www.jnj.com/media-center/press-releases/findings-from-landmark-resonate-2-study-confirm-sustained-survival-benefit-of-imbruvica-ibrutinib-for-first-line-chronic-lymphocytic-leukaemia-treatment-with-up-to-10-years-follow-up