A new study presented at ASH 2018 shows older patients with chronic lymphocytic leukaemia (CLL) have a significantly lower rate of disease progression if treated with the targeted therapy ibrutinib rather than the chemotherapy drug bendamustine plus the antibody 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 suggests adding rituximab to ibrutinib does not add benefits beyond those seen with ibrutinib alone.
CLL is a cancer of the white blood cells that is most common in older adults.
The U.S. Food and Drug Administration (FDA) approved ibrutinib as a first-line treatment for CLL in 2016.
“Our results establish that ibrutinib should be a standard of care for older patients with CLL – it is more effective than the best available chemoimmunotherapy regimen,” said lead study author Jennifer A. Woyach, MD, of The Ohio State University Comprehensive Cancer.
“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 trial enrolled 547 older patients with previously untreated, symptomatic CLL between 2013 – 2016.
Participants ranged from 65-89 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, just over three years.
Rates of survival without any disease progression at two 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 three groups at two 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 receiving ibrutinib alone.
Overall, patients responded well to all three treatment regimens, with an overall response rate (tumour reduction) of 94 percent in those receiving ibrutinib alone, 93 percent in those receiving ibrutinib plus rituximab, and 81 percent in those receiving bendamustine plus rituximab.
As seen in previous trials, ibrutinib was associated with some significant side effects.
In particular, up to 17 percent of patients receiving ibrutinib developed atrial fibrillation, an abnormal heart rhythm that increases the risk of strokes and other cardiovascular problems.
The toxicities observed in the ibrutinib arms of this trial warrant further study and caution in using this drug in all older patients, Woyach noted.
Despite the fact that CLL is most common in older people, the trial is one of just a few that have included only patients over age 65.
Most clinical trials for CLL have been conducted in younger adults.
In addition, ibrutinib’s FDA approval for first-line treatment of CLL in 2016 was based on comparison to chemotherapy with chlorambucil, a drug approved in 1957 which is considered an obsolete therapy by most clinicians.
The comparison of ibrutinib to bendamustine and rituximab is of much more interest, since the latter regimen is currently widely used for treatment of patients with CLL over age 60.
“The study highlights the importance of doing clinical trials for older patients, because the toxicities are likely to be different for older versus younger patients, even with the same drug,” said Woyach.