Ibrutinib, alone or with rituximab, outperforms bendamustine and rituximab in older patients with previously untreated chronic lymphocytic leukaemia (CLL), according to findings presented at ASH 2018.
In study released at the 2018 American Society of Hematology (ASH) Annual Meeting in San Diego, and published concurrently in the New England Journal of Medicine, 547 patients from the US and Canada were randomised to one of the three arms and followed for over three years.
Patients had an average age of 71 years (range 65-89 years) and those whose disease progressed after receiving bendamustine plus rituximab crossed over to ibrutinib as a second-line treatment.
The study found no significant different in progression free survival (PFS) between patients receiving ibrutinib alone or ibrutinib with rituximab but both groups receiving the targeted therapy did better than the group of patients receiving bendamustine.
The estimated proportion of patients with PFS at two years was 87% with ibrutinib alone, 88% with ibrutinib plus rituximab and 74% for bendamustine plus rituximab.
“The hazard ratio for disease progression or death was 0.39 (95% CI, 0.26 to 0.58) for the comparison of ibrutinib with bendamustine plus rituximab (one-sided P<0.001) and 0.38 (95% CI, 0.25 to 0.59) for the comparison of ibrutinib plus rituximab with bendamustine plus rituximab (one-sided P<0.001),” the study authors said.
“Progression-free survival was longer with the ibrutinib-containing regimens than with bendamustine plus rituximab in all cytogenetic factor–related subgroups, but the difference was greater among patients with del(17p13.1).”
However the study found there was no significant difference in overall survival between the groups (94%, 90% and 95% respectively).
In addition, the proportion of patients with undetectable minimal residual disease was significantly higher with bendamustine plus rituximab (8%) than with the ibrutinib-containing regimens (1% and 4%).
“The significantly lower rates of undetectable minimal residual disease with the ibrutinib-containing regimens than with bendamustine plus rituximab suggest that treatment with single-agent ibrutinib must be continued indefinitely,” the study authors said.
“The rate of grade 3, 4, or 5 hematologic adverse events was higher with bendamustine plus rituximab (61%) than with ibrutinib or ibrutinib plus rituximab (41% and 39%, respectively), whereas the rate of grade 3, 4, or 5 nonhematologic adverse events was lower with bendamustine plus rituximab (63%) than with the ibrutinib-containing regimens (74% with each regimen).”
“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 Dr Jennifer Woyach who presented the findings at ASH.
“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.”
Dr Woyach, from the Ohio State University Comprehensive Cancer Center, added the toxicities such as arrhythmias observed in the ibrutinib arms of the trial warrant further study.