Background: Ibrutinib, a once-daily Bruton tyrosine kinase inhibitor, is the only targeted therapy to demonstrate significant progression-free survival (PFS) and overall survival (OS) benefits in multiple randomized phase 3 studies in previously untreated and relapsed/refractory chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL). Single-agent ibrutinib is used as a continuous therapy, making oncology nurses critically important in supporting patients for maximum benefit with ibrutinib.
Objectives: To report up to 7 years of follow-up data for the RESONATE-2 study and provide experience-based nursing recommendations for educating patients on adverse event (AE) management and benefits of long-term adherence, aiming to optimize outcomes in patients with CLL/SLL receiving first-line ibrutinib.
Methods: The phase 3, open-label RESONATE-2 study compared efficacy and safety of first-line ibrutinib versus chlorambucil in older patients with CLL/SLL. Patients ≥65 years with previously untreated CLL/SLL and without del(17p) (N = 269) were randomized 1:1 to receive oral ibrutinib 420 mg once daily until disease progression (PD) or unacceptable toxicity (n = 136), or chlorambucil 0.5-0.8 mg/kg on days 1 and 15 of up to twelve 28-day cycles (n = 133). Outcomes included PFS, OS, overall response rate (ORR), and safety.
Results: After up to 7 years of follow-up (median 74.9 months; range, 0.1-86.8), ibrutinib resulted in significantly longer PFS (median not reached vs 15.0 months with chlorambucil), with 84% reduction in risk of PD or death versus chlorambucil. In patients with the high-risk genomic features del(11q) and unmutated IGHV, ibrutinib resulted in reductions of 97% and 89%, respectively, in risk of PD or death versus chlorambucil. After up to 6.5 years of ibrutinib, OS was 78%, and ORR was 92%. The complete response (CR/CRi) rate continued to deepen, with a rate of 34% at this follow-up. Rates of grade ≥3 AEs of clinical interest remained low: hypertension (5-6 year interval: 5%, n = 4; 6-7 years: 4%, n = 3), atrial fibrillation (5-6 years: 1%, n = 1; 6-7 years: 1%, n = 1), and no grade ≥3 major hemorrhage from 5-7 years. Dose reductions due to AEs decreased over time, occurring in 4% (n = 3) of patients from 5-6 years and 4% (n = 3) from 6-7 years. Ibrutinib discontinuations due to AEs also decreased, with 3% (n = 2) from 5-6 years and none from 6-7 years. The primary reason for ibrutinib discontinuation from 5-7 years was PD (5-6 years: 5%, n = 4; 6-7 years: 6%, n = 4). After up to 7 years, 47% of patients remained on ibrutinib. Nurses can educate patients on potential AEs and how active dose management can be used effectively throughout treatment. Nurses can encourage ibrutinib adherence by discussing long-term benefits of continuous therapy and/or providing medication diaries for tracking doses.
Conclusion: With up to 7 years of follow-up, first-line ibrutinib therapy demonstrated sustained PFS and OS benefits in patients with CLL, including those with high-risk genomic features. Rates of grade ≥3 hypertension, atrial fibrillation, and major hemorrhage remained low with long-term ibrutinib treatment, and discontinuations or dose reductions due to AEs were rare. Based on the long-term data available with ibrutinib, nurses can have an important role in discussing AE management and the risks and benefits of long-term ibrutinib treatment with their patients.
Sponsor: Pharmacyclics LLC, an AbbVie Company.
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