Novel Agent Efficacious in Chronic Lymphocytic Leukemia

Get Permission

3.3s.18_chart_b.jpgA novel inhibitor of B-cell receptor signaling produced high rates of remission and was well tolerated in patients with chronic lymphocytic leukemia (CLL) who were refractory to at least two previous treatments, reported Susan O’Brien, MD, of The University of Texas MD Anderson Cancer Center, Houston.1

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

New Molecular Target

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

In the study, 61 patients with CLL or small lymphocytic lymphoma who were relapsed/refractory to standard treatments received PCI-32765 daily (420 or 840 mg) in 28-day cycles. Almost three-fourths of the patients had at least one poor-risk molecular feature. Median follow-up for the 420-mg cohort was 10.2 months and for the 840-mg cohort was 6.5 months.

Responses were observed in 67% of patients receiving 420 mg and in 68% of those receiving 840 mg, with nodal partial responses seen in 23% of patients. Responses appeared to be independent of molecular risk features.

Evolving Responses

3.3s.18_winter.jpg“At the ASCO Annual Meeting, we reported partial response rates of 48%. Now we report a response rate of about 67%. The responses have evolved over time,” Dr. O’Brien noted.

Only 5% of patients have progressed; 6-month progression-free survival was 92% in the 420-mg cohort and 90% in the 840-mg cohort. Phase III trials of PCI-32765 are planned.

Jane Winter, MD, of Northwestern University Feinberg School of Medicine, Chicago, who moderated the press briefing where the results were announced, commented, “PCI-32765 is a promising new agent that is based on a novel strategy: targeting the B-cell receptor. It has a very low toxicity profile and high response rates. This is just the beginning of many new agents for the treatment of CLL and other lymphoid malignancies.” ■

Disclosure: Dr. O’Brien receives research support from and is a consultant for Pharmacyclics. Dr. Winter reported no potential conflicts of interest.


1. O’Brien S, Burger JA, Blum KA, et al: The Bruton’s tyrosine kinase inhibitor PCI-32765 induces durable responses in relapsed or refractory chronic lymphocytic leukemia/small lymphocytic lymphoma: Follow-up of a phase Ib/II study. 53rd American Society of Hematology Annual Meeting. Abstract 983. Presented December 13, 2011.