Article
Novel Agent Targeting the B-Cell Receptor Shows Efficacy, Without Myelosuppression, in Chronic Lymphocytic Leukemia
Author(s):
First drug targeting Bruton's tyrosine kinase (Btk) produced high rates of remission in patients with CLL.
Susan O'Brien, MD
A novel inhibitor of B-cell receptor signaling produced high rates of remission, and was very well tolerated, in patients with chronic lymphocytic leukemia (CLL) who were refractory to at least 2 previous treatments.
This news came from results of a study presented at the 53rd Annual Meeting of the American Society of Hematology by Susan O’Brien, MD, professor, Department of Leukemia, Division of Cancer Medicineat the University of Texas MD Anderson Cancer Center, Houston, Texas.
“To have agents that are this effective and are not myelosuppressive is very exciting,” O’Brien said at a press briefing. “Efficacy increases over time. There is a relative lack of toxicity. There is a lack of myelosuppression. These agents will really change the paradigm for the treatment of CLL.”
The agent, called PCI-32765, is the first drug designed to target Bruton’s tyrosine kinase (Btk), a protein that is essential for CLL cell survival and proliferation. Btk is a central mediator of B-cell receptor signaling, which is essential for normal B-cell development. PCI-32765 is an orally administered, irreversible inhibitor of Btk that induces apoptosis and inhibits cellular migration and adhesion in malignant B-cells.
“An early analysis of the phase Ib/II study, PCYC-1102, showed PCI-32765 to be highly active and tolerable in patients with CLL. In this study we report longer-term follow-up of this multicenter phase Ib/II trial,” O’Brien said.
The investigators enrolled 61 patients with CLL (previously untreated ≥65 years old, with relapsed/refractory [R/R] disease after at least 2 prior therapies) for treatment with oral PCI-32765 daily for 28-day cycles until progression of disease. Seventy-two percent of patients had at least one poor-risk molecular feature: del(17p) 31%, del(11q) 33%, IgVH un-mutated 57%.
Doses of 420 mg (in previously untreated and R/R patients) and 840 mg daily (in R/R patients) were examined. The patients with R/R disease were evaluated in this analysis. Median follow-up for the 420-mg cohort was 10.2 months and for the 840-mg cohort was 6.5 months.
Objective response rates (ORR) in the 420-mg cohort, previously reported as 48% after 6 months of follow-up, was 70%, at 10 months; the ORR in the 840-mg cohort was 44% at 6.5 months median follow-up. Nodal partial response has been observed in 35% of patients (>50% reduction in aggregate lymph node size), with residual lymphocytosis. The ORR appears to be independent of molecular risk features.
