An interim analysis of a large phase III study suggests that the combination of ibrutinib and bendamustine/rituximab (BR) improves outcomes for patients with chronic-lymphocytic leukemia (CLL) that worsened despite prior therapy.
At a median follow-up of 17 months, patients who received ibrutinib and BR had an 80% lower risk of disease progression or death than those who received placebo and BR. Based on this striking benefit, patients were permitted to cross over from the placebo group to receive ibrutinib.
CLL is the most common adult leukemia in Western countries. For years, the standard treatment for CLL has been a combination of chemotherapy and targeted therapy (e.g., rituximab). Although these treatments help control the disease for many years, they cannot cure it, and all patients ultimately become resistant to therapy.
Until recently, patients whose disease worsened or came back despite treatment have had limited options. Last year, however, the FDA approved two new targeted drugs for such patients ─ ibrutinib and idelalisib in combination with rituximab. Ibrutinib is a first-in-class oral once-daily targeted treatment that blocks Bruton's tyrosine kinase (BTK). This protein fuels the growth of lymphocytes, the type of white blood cells that are affected by CLL.
"This was one of the most rigorous clinical trials ever conducted in CLL and it truly validates ibrutinib as an important drug for this cancer," said lead study author Asher Chanan-Khan, MD, a professor of medicine at Mayo Clinic in Jacksonville, FL. "We found that ibrutinib can be safely paired with existing therapy to powerfully prolong remissions and improve patients' well-being."
In the study, 578 patients with previously treated CLL were randomly assigned to treatment with ibrutinib and BR or placebo and BR. After an average follow-up of 17.2 months, the median progression-free survival was 13.3 months in the placebo group and was not reached in the ibrutinib group. The risk of progression or death was decreased by 80% in those who received ibrutinib.
Response rates were significantly higher in the ibrutinib group than in the placebo group (82.7% vs. 67.8%). Disease-related fatigue improved in the ibrutinib group, and patients reported benefit sooner (at six months vs. 14 months).
At the time of the interim analysis, 90 (31%) patients from the placebo group had already crossed over to the ibrutinib group. The rates and types of side effects were comparable between the two treatment groups. The most frequent side effects were low blood cell counts and nausea.
The next steps for this area of research include evaluating ibrutinib as a single agent and in combination with drugs targeting the CD20 protein in patients with newly diagnosed, symptomatic, and asymptomatic CLL.
This study received funding from Janssen Research & Development, LLC (Janssen).