Venetoclax – new drones to deploy against chronic lymphocytic leukemia

02/2018

Prof. MUDr. Tomáš Kozák, Ph.D., MBA

Interní hematologická klinika, 3. LF UK a FNKV, Praha

SUMMARY

Venetoclax is orally available bcl-2 inhibitor effective in tumors with high antiapoptotic activity as chronic lymphocytic leukemia and some other haematological malignancies. Venetoclax also bypasses TP53 and is active in diseases with lack or mutation of TP53. All clinical studies so far have shown high activity of venetoclax in monotherapy and in combination therapy in both relapsing/refractory chronic lymphocytic leukemia and in the 1^st line. Venetoclax can induce response in 70-100% with high complete remission rate. Venetoclax is able to achieve minimal residual disease negativity in up to 60% in relapsing/refractory setting and up to 70% in 1^st line. Venetoclax is well tolerated with major toxicity being hematological. After the introduction of rump-up stepwise strategy to the initial phase of treatment the clinical tumor lysis syndrome, originally associated with venetoclax, became very rare. After final results of current clinical studies are reported we can expect significant change in the treatment strategy especially in high risk chronic lymphocytic leukemia.

KEY WORDS

venetoclax, bcl-2, apoptosis, minimal residual disease, chronic lymphocytic leukemia