Lugano 2013: Ibrutinib Highly Active in Patients with Chronic Lymphocytic Leukemia with 17p Deletion
The 17p deletion in chronic lymphocytic leukemia (CLL) is associated with worse outcome in patients receiving standard chemotherapy. The Bruton’s tyrosine kinase (BTK) inhibitor ibrutinib has shown durable antitumor activity in high-risk CLL. Adrian Wiestner, MD, PhD, of the National Institutes of Health, and colleagues reported findings of a phase II study of ibrutinib in patients who had CLL with 17p deletion in a plenary session at the 12th International Conference on Malignant Lymphoma, held June 19–22 in Lugano, Switzerland (Abstract 008). The results indicate that ibrutinib achieves rapid and durable control over disease and is associated with an acceptable safety profile.
Findings were available for the first 29 patients in the trial, with a median follow-up of 9 months. In the trial, treatment-naive patients (n = 15, age range 33–82 years) and patients with relapsed/refractory CLL (n = 14, age range 56–79 years) received oral ibrutinib 420 mg daily until disease progression. High-risk disease (Rai stage III/IV) was present in 66% of patients.
Rapid, Durable Response
At 6 months, 88% of 25 evaluable patients had a nodal response (70% median reduction in lymph node size), 48% had a partial response by International Workshop on CLL (IWCLL) criteria, and 40% had a partial response with lymphocytosis. One patient had progressive disease (presumed transformation). Nodal response was observed in 93% of the patients with relapsed/refractory disease and in 82% of treatment-naive patients.
The estimated event-free survival at 12 months was 90%. All patients exhibited a reduction in splenomegaly, with a median reduction in spleen volume of 446 mL (46%) from baseline. Bone marrow biopsy at 6 months in 23 patients showed a median 76% reduction from baseline in tumor burden as assessed by immunohistochemistry for CD79a. Fluorescence in situ hybridization measurement of percent of tumor cells with the 17p deletion at 6 months in 18 patients showed a reduction from baseline in 15 patients (median reduction, 55%), no change in 1, and an increase in 3 patients.
Treatment was well tolerated, with nonhematologic toxicities of grade 3 or higher observed in 14% of patients. Two deaths occurred during the study and were not considered treatment-related.
Potential Strategy for High-risk Patients
The investigators concluded, “Ibrutinib as a single agent is effective in both treatment-naïve and relapsed/refractory patients with 17p deletion CLL, achieving rapid control over disease in blood, nodes, spleen, and marrow that is durable with an acceptable safety profile. Ibrutinib will be further investigated as a strategy for these high-risk patients.”
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