Phase II Trial Shows Benefit of Ibrutinib in Relapsed/Refractory CLL With 17p Deletion
O’Brien et al found further evidence of the benefit of ibrutinib (Imbruvica) in relapsed/refractory chronic lymphocytic leukemia (CLL) with the 17p deletion, according to an extended analysis of the phase II RESONATE-17 trial reported in The Lancet Oncology. Ibrutinib currently is approved for use in this setting.
Study Details
In the open-label trial, 144 patients (all-treated population) with del17p CLL or small lymphocytic lymphoma (n = 7) enrolled from 40 sites in the United States, Canada, Europe, Australia, and New Zealand between January 2013 and June 2013 received ibrutinib at 420 mg once daily until progressive disease or unacceptable toxicity. The primary endpoint was overall response in the all-treated population (patient receiving at least one dose of study drug).
Patient enrollment is complete; follow-up is ongoing. Patients had a median age of 64 years and a median of two previous treatments.
Extended Analysis
At the prespecified primary analysis of overall response after a median follow-up of 11.5 months, response was observed in 64% of patients on independent review committee assessment and 83% on investigator assessment. In an extended analysis, with a median follow-up of 27.6 months, the response rate was 83% on investigator assessment, 24-month progression-free survival was 63%, and 24-month overall survival was 75%. Among 91 patients with any baseline cytopenia, sustained hematologic improvement was observed in 79%.
Safety
Treatment was discontinued due to adverse events, unacceptable toxicity, or death in 24 patients (17%). Major bleeding occurred in 9% of patients (grade 3 in 8%). Grade ≥ 3 infection occurred in 30%, including pneumonia in 13%.
In the extended analysis, 18 patients died as a result of adverse events; among these deaths, 4 were due to pneumonia; 3, to CLL; 2, to Richter’s syndrome; 2, to sepsis; 2, to myocardial infarction; and 1 each, to septic shock, encephalopathy, general deterioration in physical health, abnormal hepatic function, and renal infarction. No clinically relevant changes in IgA, IgG, or IgM were observed at 6 or 24 months.
The investigators concluded: “A high proportion of patients had an overall response to ibrutinib and the risk:benefit profile was favourable, providing further evidence for use of ibrutinib in the most difficult subset of patients with chronic lymphocytic leukaemia or small lymphocytic lymphoma. Ibrutinib represents a clinical advance in the treatment of patients with del17p chronic lymphocytic leukaemia and has been incorporated into treatment algorithms as a primary treatment for these patients.”
The study was funded by Pharmacyclics LLC, an AbbVie Company.
Susan O’Brien, MD, of the Chao Family Comprehensive Cancer Center, University of California Irvine, is the corresponding author of The Lancet Oncology article.
The content in this post has not been reviewed by the American Society of Clinical Oncology, Inc. (ASCO®) and does not necessarily reflect the ideas and opinions of ASCO®.
