Figures & data
Figure 1 Many cancer cells are able to evade apoptosis through impairment of the mitochondrial apoptotic pathway, controlled by proapoptotic (eg, BAK, BAX, BIM) and prosurvival (eg, BCL2, BCL-XL) members of the BCL2 family.
Notes: In CLL, cells show BCL2 overexpression. The BCL2 inhibitor venetoclax selectively binds to BCL2 and liberates proapoptotic proteins, inducing mitochondrial outer-membrane permeabilization and leading to caspase activation. This reaction induces apoptosis.
Abbreviation: CLL, chronic lymphocytic leukemia.
Abbreviation: CLL, chronic lymphocytic leukemia.
Figure 2 Durability of benefit with ongoing venetoclax therapy.
Notes: (A) Progression-free survival (PFS) in the expansion and dose-escalation cohorts; (B) PFS for patients with or without del(17p); (C) PFS and venetoclax-dose levels (400, <400, or >400 mg); (D) duration of complete and partial response. From N Engl J Med, Roberts AW, Davids MS, Pagel JM, et al, Targeting BCL2 with venetoclax in relapsed chronic lymphocytic leukemia, 374, 311–322, Copyright ©2016 Massachusetts Medical Society. Reprinted with permission from Massachusetts Medical Society.Citation48
Figure 3 Response to venetoclax.
Notes: (A) Cumulative incidence of overall response and CR by independent review-committee assessment. (B) Cumulative incidence of minimal residual disease-negative status in peripheral blood for all patients and for patients achieving CR or CRi by independent review-committee assessment. Kaplan–Meier curves for (C) overall survival, (D) progression-free survival (n=107), (E) duration of overall response for all responders by independent review-committee assessment (n=85), and (F) duration of overall response for all responders separated by response subgroups (independently assessed).
Abbreviations: CR, complete remission; CRi, CR with incomplete recovery of blood counts; nPR, nodular partial response.
Abbreviations: CR, complete remission; CRi, CR with incomplete recovery of blood counts; nPR, nodular partial response.
Figure 4 Venetoclax activity by compartment.
Notes: Absolute change from baseline in peripheral absolute lymphocyte count in patients with a baseline absolute lymphocyte count >5×109 cells/L (n=87) (A) and unidimensional nodal diameter (n=96) (B). Thresholds of 4×109 cells/L (A) and 15 mm (B) corresponded to requirements for complete remission. Line length indicates absolute best change from baseline; each line represents one patient, with patients arranged in descending order of baseline measurement. Nodal measurements were computed tomography scan-derived unidimensional diameters of largest target lesions for patients who had at least one follow-up computed tomography scan on study. Response categories assessed by independent review committee.
