Characteristics and Clinical Outcomes of Patients with Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma Receiving Ibrutinib for ≥5 Years in the RESONATE-2 Study

SIMPLE SUMMARY: Ibrutinib is an established standard of care in the first-line treatment of chronic lymphocytic leukemia. Since ibrutinib is given continuously, data on long-term treatment, outcomes, and safety are essential to inform clinical decision making. Here, we describe characteristics and outcomes of patients who received long-term treatment with ibrutinib for ≥5 years in the phase 3 RESONATE-2 study. More than half (58%) of the patients randomly assigned to receive ibrutinib in the RESONATE-2 study continued to benefit from ibrutinib treatment for ≥5 years, regardless of baseline characteristics. Among patients who were on ibrutinib treatment for ≥5 years, complete response rates improved over time through the 5 years. The safety profile of ibrutinib treatment for ≥5 years was consistent with previous reports and no new safety signals were identified. For patients who experienced adverse events, dose modification was effective in resolving adverse events, thereby facilitating continued treatment. ABSTRACT: Primary results from the phase 3 RESONATE-2 study demonstrated superior efficacy and tolerability with ibrutinib versus chlorambucil in patients with chronic lymphocytic leukemia (CLL)/small lymphocytic lymphoma (SLL). Here, we describe characteristics and outcomes of patients who received ibrutinib treatment for ≥5 years in RESONATE-2. Patients aged ≥65 years with previously untreated CLL/SLL, without del(17p), were randomly assigned 1:1 to once-daily ibrutinib 420 mg until disease progression/unacceptable toxicity (n = 136) or chlorambucil 0.5–0.8 mg/kg for ≤12 cycles (n = 133). Baseline characteristics in ibrutinib-randomized patients (n = 136) were generally similar between patients on ibrutinib treatment for ≥5 years (n = 79) versus those on treatment for <5 years (n = 57). In patients on ibrutinib treatment for ≥5 years, complete response rates improved over time, reaching 42% by 5 years. Estimated 7-year progression-free survival and overall survival rates were 82% and 94%, respectively. Adverse events (AEs) led to dose reductions in 16/79 patients (20%); these AEs were resolved for 13/16 patients (81%). AEs led to dose holds (≥7 days) in 45/79 patients (57%); these AEs were resolved for 43/45 patients (96%). More than half (58%) of ibrutinib-randomized patients benefitted from ibrutinib treatment for ≥5 years regardless of baseline characteristics. Dose modification resolved AEs for most patients, thereby facilitating continued treatment.