Background: Ibrutinib is the only once-daily Bruton tyrosine kinase inhibitor that has shown significant progression-free survival (PFS) and overall survival (OS) benefits in patients with chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL) across multiple randomized phase 3 studies. Given that single-agent ibrutinib is administered as continuous therapy, nurses are key to providing patient education and support for continuous treatment to ensure maximal benefit with ibrutinib.
Objectives: To report data from long-term follow-up of the RESONATE-2 study that evaluated first-line ibrutinib versus chlorambucil in older patients with CLL/SLL and to offer experience-based recommendations for education and management of patients with CLL.
Methods: In the phase 3 RESONATE-2 study, patients with previously untreated CLL/SLL without 17p deletion who were aged ≥65 years (N = 269) were randomized 1:1 to 420 mg once-daily ibrutinib as continuous treatment (n = 136) or treatment with 0.5 to 0.8 mg/kg chlorambucil for ≤12 cycles (n = 133).
Results: After a median follow-up of 5 years (range, 0.1-66 months), patients treated with ibrutinib had sustained PFS benefit versus those treated with chlorambucil. Median PFS was not reached with ibrutinib versus 15 months with chlorambucil; 5-year PFS estimates were 70% versus 12%, respectively. Ibrutinib treatment also resulted in improved 5-year OS rate (83%) compared with chlorambucil (68%). Patients with high-risk genomic features (unmutated IGHV, 11q deletion, and/or TP53 mutation) also experienced superior PFS and OS with ibrutinib treatment. The overall response rate for patients receiving ibrutinib was 92%, with complete responses (including complete responses with incomplete marrow recovery) increasing over time, from 11% at a median of 18 months to 30% at a median of 5 years. The most frequent grade ≥3 adverse events (AEs) included neutropenia (13%) and pneumonia (12%). The rate of most AEs, as well as the rate of dose reductions and discontinuations due to AEs, decreased over time. More than half of patients (58%) remained on ibrutinib therapy, and the rate of discontinuations due to disease progression during ibrutinib treatment was low (6%). Nurses are frequently the first healthcare providers that patients with CLL meet, performing initial patient history reviews (eg, CLL-related symptoms, comorbidities, concomitant medications) that are then provided to patients’ care teams. Nurses have an important role in educating patients on the benefits of continuous ibrutinib therapy and the expected side effects. Nurses may be the first to identify AEs and may either manage those AEs or escalate them to the treating physicians for recommendations and further management. To optimize patients’ understanding of AEs, the nurse care team might review written materials with patients.
Conclusions: In the RESONATE-2 study, single-agent ibrutinib showed sustained survival benefit and was well tolerated. Nurses play a key role in educating patients to reinforce their understanding of the benefits of continuous ibrutinib therapy and expectations regarding potential side effects, and by guiding AE management by communicating AE details to the care team.
Sponsor: Pharmacyclics LLC, an AbbVie Company.
