Ibrutinib delays progression versus chemoimmunotherapy in older CLL patients
medwireNews: Treatment with ibrutinib either alone or in combination with rituximab significantly delays disease progression or death compared with bendamustine plus rituximab in older patients with untreated chronic lymphocytic leukaemia (CLL), phase III trial data show.
According to data published in The New England Journal of Medicine and simultaneously presented at the 60th American Society of Hematology Annual Meeting in San Diego, California, USA, progression-free survival (PFS) at 2 years was estimated to be 87% among 182 patients aged 65 years or older who had previously untreated CLL and were randomly assigned to receive continuous ibrutinib (420 mg/day).
The predicted 2-year PFS rate was similar, at 88%, among the 182 patients who received ibrutinib in combination with rituximab (375 mg/m2 per week for 6 cycles) but significantly lower, at 74%, among the 183 treated with bendamustine (90 mg/m2 on days 1 and 2 of each cycle for 6 cycles) plus rituximab (375 mg/m2 per week in cycle 1 and 500 mg/m2 per week in subsequent cycles).
Indeed, compared with bendamustine plus rituximab, treatment with ibrutinib alone or in combination with rituximab was associated with significant 61% and 62% reduced risks for disease progression or death, respectively.
By contrast, there was no significant difference in PFS between the two ibrutinib regimens.
Patients in the ibrutinib and ibrutinib plus rituximab groups also had a significantly higher response rate than those in the bendamustine plus rituximab group (93% and 94% vs 81%), but a significantly lower rate of undetectable minimal residual disease (1% and 4% vs 8%).
This finding raises the question of “whether indefinite therapy with a [Bruton’s tyrosine kinase] inhibitor is needed”, Jennifer Woyach (Ohio State University Comprehensive Cancer Center, Columbus, USA) and co-authors remark.
“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”, they add, noting that treatments with combined targeted therapies may help to address this issue and will be evaluated in future studies.
During the median 38-month follow-up period, 66 patients died overall with no significant difference in overall survival (OS) observed among the three treatment groups. At 2 years, estimated overall survival was 90%, 94% and 95% with ibrutinib, ibrutinib plus rituximab and bendamustine plus rituximab, respectively.
Among the adverse events of special interest, patients who received ibrutinib or ibrutinib plus rituximab had fewer grade 3 or higher haematological events than those who received bendamustine plus rituximab (41% and 39% vs 61%, respectively), but the incidence of grade 3 or higher nonhaematological events was higher with ibrutinib or ibrutinib plus rituximab (74% and 74% vs 63%).
Woyach et al conclude that their findings “show the efficacy of treatment with continuous ibrutinib among patients with untreated CLL”.
They add: “An ongoing National Clinical Trials Network (NCTN) trial […] aims to evaluate whether treatment with ibrutinib plus rituximab is superior to chemoimmunotherapy among younger adults.”
By Laura Cowen
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