ASH 2018: Ibrutinib Alone or in Combination With Rituximab vs Bendamustine Plus Rituximab in Older Patients With CLL
A new study presented by Woyach et al at the 2018 American Society of Hematology (ASH) Annual Meeting & Exposition (Abstract 6) showed that older patients with chronic lymphocytic leukemia (CLL) have a significantly lower rate of disease progression if treated with ibrutinib rather than bendamustine plus rituximab—the combination regimen previously considered to be one of the most effective therapies for this group of patients. The study, which is the first head-to-head comparison between these treatment regimens, also suggested that adding rituximab to ibrutinib does not offer any benefit beyond that seen with ibrutinib alone.
“Our results establish that ibrutinib should be a standard of care for older patients with CLL,” said lead study author Jennifer A. Woyach, MD, of The Ohio State University Comprehensive Cancer Center, in a statement. “The findings also suggest that when designing trials for CLL in older patients, ibrutinib is the efficacy standard by which other drugs should be measured.” The U.S. Food and Drug Administration (FDA) approved ibrutinib as a first-line treatment for CLL in 2016.
Study Methods and Results
The trial enrolled 547 older patients with previously untreated, symptomatic CLL between 2013 and 2016. Participants ranged from 65 to 89 years old. One-third were randomly assigned to receive bendamustine plus rituximab, one-third received ibrutinib plus rituximab, and one-third received ibrutinib alone. Researchers tracked patient outcomes for a median of 38 months.
The rates of survival without any disease progression at 2 years (the study’s primary endpoint) were significantly better in patients who received ibrutinib plus rituximab (88%) and ibrutinib alone (87%) compared with bendamustine plus rituximab (74%). However, there was no difference in overall survival among the 3 groups at 2 years. In this study, patients whose disease progressed after receiving bendamustine plus rituximab crossed over to receive ibrutinib as a second-line treatment.
The addition of rituximab to ibrutinib did not appear to improve outcomes compared with ibrutinib alone. Overall, patients responded well to all 3 treatment regimens, with an overall response rate of 94% in those receiving ibrutinib alone, 93% in those receiving ibrutinib plus rituximab, and 81% in those receiving bendamustine plus rituximab.
As seen in previous trials, ibrutinib was associated with some significant side effects. In particular, up to 17% of patients receiving ibrutinib developed atrial fibrillation. The toxicities observed in the ibrutinib arms of this trial warrant further study and caution in using this drug in all older patients, Dr. Woyach noted.
Despite the fact that CLL is most common in older people, the trial is one of just a few that have included patients older than age 65 alone. Most clinical trials for CLL have been conducted in younger adults. The comparison of ibrutinib to bendamustine and rituximab is of much more interest, since the latter regimen is currently widely used in the treatment of patients with CLL older than age 60.
“The study highlights the importance of doing clinical trials for older patients, because the toxicities are likely to be different for older vs younger patients, even with the same drug,” said Dr. Woyach.
Disclosure: See the study authors’ full disclosures at ash.confex.com.
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