Dr. Smith on the Rationale Behind the Fixed Duration Trial for Ibrutinib/Venetoclax in CLL

Mitchell R. Smith, MD, PhD
Published: Tuesday, Dec 10, 2019



Mitchell R. Smith, MD, PhD, division director, Cancer and Blood Disorders, and professor of medicine, GW Cancer Center, discusses the rationale behind the trial looking at the fixed duration of the ibrutinib (Imbruvica) and venetoclax (Venclexta) combination in chronic lymphocytic leukemia (CLL).

Preclinical data showed there was synergy between ibrutinib and venetoclax, which makes sense, according to Smith, because ibrutinib blocks site signaling and venetoclax promotes cell death. Ibrutinib and venetoclax are opposites in terms of proliferation and lack of apoptosis, adds Smith.

Although there was some apprehension regarding the ibrutinib/venetoclax combination, data from the early studies looked promising enough, specifically the depth of response, to warrant formal examination, explains Smith. In chronic myeloid leukemia (CML), TKI treatment can be stopped, but only in certain patients who reach minimal residual disease negativity for a few years. Even then, stopping TKI treatment must be done very carefully, says Smith. In CML, there was evidence to suggest that TKI treatment could be stopped during pregnancy and that the response would be regained. Therefore, researchers began to consider that TKIs and small molecule inhibitors may be different than chemotherapy in the treatment of patients with CLL, concludes Smith.
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Mitchell R. Smith, MD, PhD, division director, Cancer and Blood Disorders, and professor of medicine, GW Cancer Center, discusses the rationale behind the trial looking at the fixed duration of the ibrutinib (Imbruvica) and venetoclax (Venclexta) combination in chronic lymphocytic leukemia (CLL).

Preclinical data showed there was synergy between ibrutinib and venetoclax, which makes sense, according to Smith, because ibrutinib blocks site signaling and venetoclax promotes cell death. Ibrutinib and venetoclax are opposites in terms of proliferation and lack of apoptosis, adds Smith.

Although there was some apprehension regarding the ibrutinib/venetoclax combination, data from the early studies looked promising enough, specifically the depth of response, to warrant formal examination, explains Smith. In chronic myeloid leukemia (CML), TKI treatment can be stopped, but only in certain patients who reach minimal residual disease negativity for a few years. Even then, stopping TKI treatment must be done very carefully, says Smith. In CML, there was evidence to suggest that TKI treatment could be stopped during pregnancy and that the response would be regained. Therefore, researchers began to consider that TKIs and small molecule inhibitors may be different than chemotherapy in the treatment of patients with CLL, concludes Smith.



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