William G. Wierda, MD, PhD
The approval of the first small-molecule targeted therapy for patients with chronic lymphocytic leukemia (CLL) launches a new era that may transform management of the disease, yet significant challenges in translating research advances into improvements for long-term outcomes remain, according to William G. Wierda, MD, PhD, a leading researcher in the field. Wierda discussed emerging therapies for CLL during an interview at the 18th Annual International Congress on Hematologic Malignancies, mid-February 2014 in New York City.
The conference occurred within days of the FDA’s accelerated approval of ibrutinib (Imbruvica) for patients with CLL who have received at least one prior therapy. Ibrutinib, the first Bruton tyrosine kinase (BTK) inhibitor on the market, was approved in November for the treatment of patients with mantle cell lymphoma who have received at least 1 prior therapy.
TABLE. Targeted CLL Therapies in Development1,2
aSponsors and collaborators may not be participating in every clinical trial for a given agent.
bIbrutinib is FDA-approved for patients with CLL who have received at least 1 prior therapy. CLL indicates chronic lymphocytic leukemia; del, deletion on short arm of chromosome.
1. Wierda WG. 17p del CLL patients—first-line vs relapsed/refractory. Presented at: 18th Annual International Congress on Hematologic Malignancies: Focus on Leukemias, Lymphomas, and Myeloma. February 14-15, 2014; New York, NY.
2. NIH Clinical Trials Registry. www.ClinicalTrials.gov.
In CLL, ibrutinib demonstrated an overall response rate of 58.3% (95% CI: 43.2%-72.4%) among 48 heavily pretreated patients with a median age of 67 years (range, 37-82 y).1
All responses were partial. The duration of response (DOR) ranged from 5.6 months to greater than 24.2 months, with the median DOR not yet reached. The indicated dose is 420 mg daily orally. It remains to be seen whether or not ibrutinib and other targeted therapies will transform CLL like imatinib (Gleevec), a tyrosine kinase inhibitor (TKI), helped transform treatment of chronic myeloid leukemia. Already, ibrutinib is among a growing list of other targeted inhibitors under development for CLL (Table
The four major groups of inhibitors target BTK, phosphatidylinositol 3-kinase (PI3K), the spleen tyrosine kinase (Syk), and BCL2 proteins.
“It is the whole class of agents that is transformative,”said Wierda, a professor and center medical director in the department of leukemia at The University of Texas MD Anderson Cancer Center in Houston, Texas, who also served on the program committee for the conference. “We’re entering a phase of a more targeted treatment approach and hopefully a less chemoimmunotherapy/chemotherapybased era.