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First evidence of single agent activity of BCL-2 inhibitor venetoclax

T-cell prolymphocytic leukemia (T-PLL) is a rare and aggressive T-lymphoid malignancy usually refractory to current treatment strategies and associated with a short overall survival. A group of researchers from Vienna led by CeMM and in collaboration with colleagues from the LBI-CR pursued to identify novel effective treatments for T-PLL patients by functional testing of primary patient-derived lymphoma cells using a library of 106 FDA-approved anti-cancer drugs or compounds currently in clinical development. They found that the BCL-2 inhibitor venetoclax (ABT-199) demonstrated the strongest T-PLL specific response when comparing individual ex vivo drug response in 86 patients with refractory hematologic malignancies. Mechanistically, responses to venetoclax correlated with protein expression of BCL-2 but not with otehr BCL-2 family members. Based on the ex vivo responses venetoclax treatment was commenced in two late stage refractory T-PLL patients resulting in favourable clinical responses. Our findings demonstrate first evidence of single agent activity of venetoclax both, ex vivo and in human offering a novel agent in T-PLL.

This report was recently published in the prestigious journal Blood.