Targeted Therapies Usher in a New Era in CLL: Wierda Discusses Key Facets of Emerging Agents
Published Online: Friday, April 4, 2014
William G. Wierda, MD, PhD
Wierda discussed emerging therapies for the most prevalent form of adult leukemia in an interview during the 18th Annual International Congress on Hematologic Malignancies®: Focus on Leukemias, Lymphomas, and Myeloma. Physicians’ Education Resource® , LLC, hosted the conference on February 14-15 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 one prior therapy.
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 dosage is 420 mg daily orally.
It remains to be seen what impact ibrutinib and other targeted therapies will have over the long term in CLL. In chronic myeloid leukemia (CML), imatinib (Gleevec), a tyrosine kinase inhibitor (TKI), has helped transform the natural history of the disease.
Already, ibrutinib is among a growing list of 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 PER conference. “We’re entering a phase of a more targeted treatment approach and hopefully a less chemoimmunotherapy/ chemotherapy- based era.
“We will see a clear improvement in outcomes for patients with CLL, and when I think in terms of during my career, this is clearly a transformative period with significant incremental advances in therapy, particularly for the elderly who have difficulty tolerating myelosuppressive chemoimmunotherapy, and for patients with 17p CLL, for whom we have no effective treatment,” noted Wierda, who has been conducting research in CLL for more than a decade.
However, Wierda said the introduction of TKIs to the armamentarium for CLL would likely present issues of resistance like what was experienced in CML and other tumor types.
“Our work is not done,” he said. “We still have a lot of issues to address, and I think there still is clearly room for advances in treatments for patients with CLL.”
Ibrutinib is the second new therapy that the FDA approved for patients with CLL in less than four months. In November, the agency approved the monoclonal antibody obinutuzumab (Gazyva) in combination with chlorambucil for patients with previously untreated CLL.
Wierda, who serves on the National Comprehensive Cancer Network (NCCN) committee that develops guidelines for treatment of CLL, said the panel has incorporated data concerning both ibrutinib and obinutuzumab into the latest update, and will further review the new therapies at its meeting in late June. In an interview with OncologyLive, Wierda discussed the emerging targeted therapies, including issues in translating new regimens into clinical practice.
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