By Laura Cowen
The experimental drug ibrutinib (PCI-32765) is highly active and well tolerated in elderly, treatment-naive patients with chronic lymphocytic leukemia (CLL), US researchers report.
The findings arise from a phase Ib/II trial evaluating two doses of single-agent ibrutinib in patients aged 65 years and older (median 71 years) who require stem-cell transplantation for treatment of active CLL.
John Byrd (Ohio State University Comprehensive Cancer Center, Columbus, USA) and colleagues explain that standard treatment with fludarabine-based therapy, although effective, carries a significant risk for morbidity and mortality in elderly patients. Therefore, older CLL patients represent a high priority for new therapeutic approaches.
Ibrutinib is one such approach. It is the first drug designed to target Bruton's tyrosine kinase, a protein that is essential for CLL-cell survival and proliferation, the researchers note.
Study participants were treated with oral ibrutinib at doses of 420 mg (n=26) or 840 mg (n=5) administered daily for 28-day cycles until disease progression.
With a median follow up of 10.7 months, 73% of patients in the 420 mg cohort achieved a response according to 2008 International Workshop on CLL criteria. Partial responses accounted for 65%, while the remaining 8% experienced complete remission with no morphologic evidence of CLL in marrow.
An additional 12% of patients in this group achieved nodal responses with lymphocytosis.
Byrd and team estimate that 12-month median progression-free survival for the 420 mg cohort is 93%.
The 840 mg cohort was terminated after activity and safety were found to be similar to that of the 420 mg group. Among the patients in the 840 mg cohort, followed up for a median of 4.6 months, two achieved a partial response and one achieved a nodal response.
The researchers report that the majority of adverse events were grade 2 or less in severity, most commonly diarrhea, nausea, and fatigue.
Grade 3 or 4 nonhematologic adverse events potentially related to ibrutinib occurred in 19% of patients and 10% experienced grade 3 or 4 infections or cytopenias.
"This interim report indicates that older patients respond well to this oral, targeted therapy, which lacks many of the side effects of chemotherapy and produces a quite dramatic 1-year progression-free survival," said Byrd in a press statement.
"The high overall response rate and lack of side effects suggests that ibrutinib deserves further study as a first-line treatment in elderly CLL patients," he concluded.
The study findings were due to be presented at the 2012 American Society for Clinical Oncology Annual Meeting in Chicago, Illinois, at the time of writing.
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