Background: Ibrutinib, a first-in-class, once-daily inhibitor of Bruton tyrosine kinase, is approved in the US for CLL/SLL treatment, including in combination with obinutuzumab. The combination of ibrutinib-obinutuzumab versus chlorambucil-obinutuzumab was investigated in patients with previously untreated CLL in an international, randomized phase 3 study, iLLUMINATE (PCYC-1130; NCT02264574).
Objectives: To educate on nursing practices for monitoring adverse events (AEs) and providing patient education when treating with ibrutinib.
Methods: Eligible patients had previously untreated CLL/SLL requiring treatment and were aged ≥65 years or <65 years with coexisting conditions. Patients were randomized (1:1) to receive ibrutinib (420 mg once daily continuously) plus 6 cycles of obinutuzumab infusion (1000 mg on days 1/2, 8, and 15 of cycle 1; day 1 of cycles 2-6), or 6 cycles of oral chlorambucil plus obinutuzumab.
Results: Among 229 randomized patients, median age was 71 years (range, 40-87), with Cumulative Illness Rating Scale score >6 in 32% and baseline cytopenia in 55%; 65% had high-risk genomic features defined as del(17p), del(11q), TP53 mutation, or unmutated IGHV. With median follow-up of 31.3 months, progression-free survival was significantly prolonged for patients on ibrutinib-obinutuzumab versus chlorambucil-obinutuzumab (median not reached [NR] vs 19.0 months), including in the high-risk population (median NR vs 14.7 months). Overall response rates were 88% with ibrutinib-obinutuzumab and 73% with chlorambucil-obinutuzumab; complete response (with/without bone marrow recovery) rates were 19% versus 8%. In patients with baseline thrombocytopenia, sustained improvement in platelet counts during the first 6 months of therapy occurred in 32% on ibrutinib-obinutuzumab and 27% on chlorambucil-obinutuzumab; in patients with anemia, improvement in hemoglobin occurred in 51% and 42%, respectively. Nurses provided symptoms-based education on hematologic improvements and how that impacted patient health, which was important for educating patients on the benefits of continuing therapy. With up to 3 years follow-up, 70% of ibrutinib-obinutuzumab patients remained on single-agent ibrutinib therapy. Most common reasons for ibrutinib discontinuation included AEs (16%) and progression (4%). Median treatment duration was 29.3 months with ibrutinib-obinutuzumab and 5.1 months with chlorambucil-obinutuzumab. Infusion-related reactions (IRRs) with obinutuzumab occurred less frequently with ibrutinib-obinutuzumab than chlorambucil-obinutuzumab (any grade, 25% vs 58%; grade ≥3 or serious, 3% vs 9%); no patients discontinued obinutuzumab infusions due to IRR with ibrutinib-obinutuzumab, versus 7 (6%) for chlorambucil-obinutuzumab. Nurses have key roles in discussing AE recognition and management with patients, including explaining IRR management plans (eg, medications to help prevent and treat IRRs) to ease patients’ anxiety. During infusions, nurses monitored patients closely to detect any early signs/symptoms of IRR. Other common AEs (>25%) with ibrutinib-obinutuzumab were neutropenia (43%), thrombocytopenia (35%), diarrhea (34%), and cough (27%). Nurses monitored for cytopenias and infection risk with regular evaluation of blood counts, and educated patients on signs/symptoms of fever and infection.
Conclusion: First-line combination therapy with ibrutinib-obinutuzumab represents an effective chemotherapy-free regimen for patients with CLL and is associated with significantly improved PFS and fewer IRRs versus chlorambucil-obinutuzumab. Oncology nurses play critical roles in educating patients, monitoring AEs, and supporting the management of patients receiving continuous ibrutinib therapy to help achieve maximal treatment benefit.
Sponsor: Pharmacyclics LLC, an AbbVie Company.