In vitro sensitivity of CLL at screening does not predict for clinical outcomes. (A) Lymphocyte response. For patients with lymphocytosis >5 × 10⁹/L at screening, the percentage reduction in lymphocyte count at week 6 on venetoclax did not correlate with the screening in vitro sensitivity (n = 13; R² < 0.001). Data points are color coded by cohort dose (≥400 mg in black or <400 mg in gray); lack of correlation is not explained by differences in dose of venetoclax (R² = 0.001 for patients receiving ≥400 mg/d only). (B) Nodal response. The percentage reduction in the lymph node mass (represented by the SPD of 6 target lesions on CT) at week 6 on venetoclax did not correlate with the screening in vitro sensitivity (n = 22; R² = 0.07). Data points color coded by cohort dose (≥400 mg in black or <400 mg in gray); lack of correlation is not explained by differences in dose of venetoclax (R² < 0.01 for patients receiving ≥400 mg/d only). (C) Marrow response. The percentage reduction in BM CLL infiltration at week 24 on venetoclax did not correlate with screening in vitro sensitivity (n = 17; R² = 0.006). Data points color coded by cohort dose (≥400 mg in black or <400 mg in gray); lack of correlation is not explained by differences in dose of venetoclax (R² = 0.006 for patients receiving ≥400 mg/d only). (D) Best iwCLL response. Correlation between screening PB CLL LC₅₀ and overall best objective response to venetoclax observed for 22 CLL patients on the M12-175 study as judged by iwCLL criteria (ANOVA P = .42). Data points color coded by cohort dose (≥400 mg in black or <400 mg in gray); lack of correlation is not explained by differences in dose of venetoclax (ANOVA P = .47 for patients receiving ≥400 mg/d only). CR, complete remission or complete remission with incomplete count recovery; PR, partial response; SD, stable disease.