Background: Ibrutinib, a first-in-class, once-daily inhibitor of Bruton tyrosine kinase (BTK), is approved in the US for the treatment of CLL/SLL and allows for treatment without chemotherapy. The phase 3 RESONATE study (NCT01578707) evaluated efficacy and safety of ibrutinib compared with ofatumumab in patients with relapsed/refractory CLL/SLL.
Objective: To educate on nursing and patient counseling practices in managing adverse events (AEs) and concomitant medications with ibrutinib therapy, based on data from the final analysis of RESONATE with up to 6 years of follow-up on ibrutinib.
Methods: Patients with relapsed/refractory CLL were randomized to receive oral ibrutinib 420 mg once-daily continuously (until progression) or intravenous ofatumumab for 24 weeks. Efficacy end points, including progression-free survival (PFS) and response, were investigator-assessed.
Results: Among 391 patients randomized (n = 195, ibrutinib; n = 196, ofatumumab), median age was 67 years (range, 30-88 years). Median follow-up in the ibrutinib arm was 65 months (range, 0.3-72 months). Ibrutinib was associated with significant, sustained PFS benefit versus ofatumumab, with median PFS of 44 versus 8 months, respectively. Best overall response rate with ibrutinib was 91%; complete response (with/without complete bone marrow recovery) increased over time to 11% with continuous ibrutinib up to 6 years. Median duration of ibrutinib treatment was 41 months, with 41% of patients treated for >4 years. Most common reasons for ibrutinib discontinuation prior to study closure were progression (37%) and AEs (16%). Nurses educated patients on AE recognition and management while emphasizing the importance of reporting concomitant medications and changes in medications. Most common cumulative AEs of any grade (>30%) with ibrutinib were diarrhea (62%), fatigue (42%), cough (40%), upper respiratory tract infection (40%), pyrexia (37%), nausea (35%), anemia (32%), and neutropenia (31%). Prevalence of grade ≥3 AEs with ibrutinib decreased after the first year and remained stable thereafter. Nurses monitored for cytopenias with regular evaluation of blood counts, reported changes to the physician, counseled patients regarding results, and educated patients to report all illnesses, fevers, and infections. The prevalence of most grade ≥3 AEs of clinical interest (including cytopenias, pneumonia, diarrhea, fatigue, and atrial fibrillation) with ibrutinib decreased over time, with the exception of hypertension. During long-term ibrutinib therapy, hypertension of any grade occurred in 21% of patients (grade ≥3, 9%), with median time to onset of 14 months. Nurses monitored patients for new-onset hypertension and educated patients on changes to antihypertensive medications. Grade ≥3 infections were experienced by 45% of ibrutinib-treated patients cumulatively, occurring at a median time to onset of 7 months; these events were most frequent during the first year and decreased over time. Nurses monitored patients for signs of infections and recommended initiation of antimicrobial treatments, as appropriate.
Conclusion: Long-term treatment with ibrutinib was associated with sustained, significant efficacy benefits and tolerability in patients with R/R CLL, with low rates of treatment discontinuation due to AEs. Oncology nurses play an essential role in optimizing patient benefit from ibrutinib by educating and supporting patients in identifying and managing AEs, monitoring concomitant medications, and providing ongoing communication between the patient and care team during ibrutinib treatment.
Sponsor: Pharmacyclics LLC, an AbbVie Company.