Lindsey Roeker, MD, hematologic oncologist, Memorial Sloan Kettering Cancer Center, discusses the rationale for combining venetoclax (Venclexta) with BTK inhibitors for use in patients with chronic lymphocytic leukemia (CLL).

Because CLL cells are B cells that have undergone changes to their genetic code, they do things that other B cells would not do. For example, CLL cells make copies of themselves and do not die after a normal lifespan, according Roeker. However, the combination of BTK inhibitors, which are cytostatic, and venetoclax, which is cytotoxic, allows for the targeting of both mechanisms of proliferation and survival of CLL , Roeker says. 

Additionally, BTK inhibitors and venetoclax are effective in different ways, Roeker adds. BTK inhibitors appear to be more effective in targeting nodal disease, whereas venetoclax is effective in targeting peripheral disease. By combining these therapies together, CLL cells can be driven out of the lymph nodes and eliminated in the peripheral blood, Roeker concludes.

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Lindsey Roeker, MD, discusses the rationale for combining venetoclax with BTK inhibitors for use in patients with chronic lymphocytic leukemia.

Dr. Roeker on the Rationale for BTK/Venetoclax Combos in CLL 

Lindsey Roeker, MD, hematologic oncologist, Memorial Sloan Kettering Cancer Center, discusses the emerging role of minimal residual disease (MRD) as a predictive end point in chronic lymphocytic leukemia (CLL).

Understanding how to optimize MRD is developing in CLL, Roeker says. Clinical trials evaluating combined-modality regimens are including MRD as a predictive end point for response, Roeker explains. 

A correlation between MRD negativity and prolonged progression-free survival (PFS) has been observed in patients with CLL treated with chemoimmunotherapy, Roeker says. Additionally, findings from the phase 3 MURANO trial (NCT02005471) demonstrated that undetectable MRD (uMRD) was associated with improved PFS, as well as overall survival, in patients with relapsed/refractory CLL, Roeker adds.

Additional research with ongoing trials is needed to determine whether uMRD can predict for long-term PFS benefit or whether fixed-duration treatment is a sufficient and simpler way to treat patients with CLL, Roeker concludes.

Lindsey Roeker, MD, discusses the emerging role of minimal residual disease as a predictive end point in chronic lymphocytic leukemia.



Lindsey Roeker, MD

Articles

Dr. Roeker on the Rationale for BTK/Venetoclax Combos in CLL

Dr. Roeker on the Emerging Role of MRD in CLL