Background: Ibrutinib, a B-cell receptor pathway inhibitor, is approved in the United States for the treatment of patients with chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL) and allows for treatment without chemotherapy. Ibrutinib is an oral treatment taken once daily at a dose of 420 mg (3 capsules) until disease progression or unacceptable toxicity. In this open-label phase 1b/2 study, single-agent ibrutinib demonstrated efficacy and tolerability in patients with both treatment-naive (TN) and relapsed/refractory (R/R) CLL/SLL after approximately 5 years of treatment, the longest follow-up to date for ibrutinib-treated patients. Nurse navigators can educate patients about maximizing the long-term benefits of ibrutinib by adherence to therapy and adverse event (AE) management.
Objective: Report the efficacy and safety results of the phase 1b/2 study after 5 years of treatment.
Methods: Patients with CLL/SLL were given ibrutinib until disease progression or unacceptable toxicity. Long-term efficacy and safety outcomes were evaluated.
Results: Of 132 ibrutinib-treated patients (23% TN, 77% R/R) followed for a median of 56 months, 89% responded to treatment. The rates of complete response increased over time with extended treatment from 6% at 1 year to 29% at 5 years in TN patients and from 3% at 1 year to 10% at 5 years in R/R patients. An estimated 92% of TN and 43% of R/R patients were alive and had not progressed at month 60; 92% of TN and 57% of R/R patients were estimated to be alive at month 60. Survival outcomes were greater in patients who had fewer prior lines of treatment. Ibrutinib was generally well tolerated, with AEs leading to discontinuation in 25% and dose reduction in 13% of patients. The most frequent grade ≥3 AEs were hypertension (26%), pneumonia (22%), neutropenia (17%), and atrial fibrillation (9%). The onset of new grade ≥3 AEs was greatest during the first year of treatment and decreased during subsequent years. Additionally, AEs leading to dose reductions and discontinuations occurred more frequently in the first year compared with subsequent years with continued treatment. Of all treated patients, 61% of TN and 30% of R/R patients continue taking ibrutinib on study. Additional guidance on strategies to manage common AEs associated with ibrutinib use will also be presented.
Conclusions: After 5 years of follow-up, single-agent ibrutinib provided substantial disease control and sustained survival benefit. Patients who received ibrutinib earlier in their treatment course experienced better survival outcomes. The best response to ibrutinib improved over time, with more patients achieving a complete response after prolonged treatment. Nurse navigators can play a key role in educating patients about the benefits of taking ibrutinib continuously at the full recommended dose to achieve long-term clinical benefits. Nurse navigators can also inform patients about AEs that they may experience and instruct patients on when to contact their care team with questions or concerns. Because ibrutinib is taken orally once daily, patients can achieve disease control and survival benefits without frequent clinic visits; however, it is critical that nurse navigators set up follow-up care and communication plans with their patients.
