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Novel Oral B-Cell Receptor Inhibitor Very Effective in Chronic Lymphocytic Leukemia

Response Rates Increasing Over Time, with Low Toxicities
February 2012 Vol 5, No 1, Special Issue - Leukemia

A novel inhibitor of B-cell receptor signaling, PCI-32765, produced high rates of remission and was well tolerated in patients with chronic lymphocytic leukemia (CLL) whose disease was refractory to at least 2 previous treatments, reported Susan O’Brien, MD, of the University of Texas M.D. Anderson Cancer Center, Houston.

 “To have agents that are this effective and that are not myelosuppressive is very exciting,” Dr O’Brien said. “These agents will change the paradigm for the treatment of CLL.”  

PCI-32765 is the first drug designed to target Bruton’s tyrosine kinase, a protein that is essential for CLL cell survival and proliferation.

A total of 61 patients with relapsed or refractory CLL received oral PCI-32765 daily (420 mg in previously untreated and 840 mg in previously treated patients) for 28-day cycles or until disease progression. At least 1 poor-risk molecular feature was present in 72% of patients. Median follow-up was 10.2 months for the 420-mg cohort and 6.5 months for the 840-mg cohort.

Response rates were 70% in the 420-mg cohort and 44% in the 840-mg group. Nodal partial responses (PRs) were reported in 35% of patients (>50% reduction in aggregate lymph node size), with residual lymphocytosis. Reponses appear to be independent of molecular risk features.  

Dr O’Brien noted that response rates have steadily increased over the duration of the study. “At ASCO, we reported a PR rate of 48%. Now we report a response rate of about 70%. The responses have evolved over time,” she said.

Some 82% of the original patients are still using this treatment; only 8% of patients have progressed so far. The 6-month progression-free survival was 92% in the 420-mg cohort and 90% in the 840-mg cohort.

PCI-32765 is well tolerated, with most adverse events reported being grade 1 or 2. Myelosuppression has not been a problem with this agent, Dr O’Brien said. Phase 3 clinical trials with PCI-32765 are planned.

Jane Winter, MD, Professor of Med­icine at Northwestern Univer­sity Feinberg School of Medicine, Chicago, who moderated the press briefing, commented, “This appears to be a highly effective new agent, with a new strategy that targets the B-cell receptor. It has a very low toxicity profile and high efficacy, and it is just the beginning of many new agents in CLL.”
 

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Last modified: August 30, 2021
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