Phase I interim safety and efficacy of venetoclax (ABT-199/GDC-0199) monotherapy for relapsed/refractory (R/R) multiple myeloma (MM).

8576 Background: The anti-apoptotic protein BCL-2 has been implicated in mediating the survival of MM cells. Venetoclax (VEN) is a potent, selective, orally bioavailable small-molecule BCL-2 inhibitor. VEN induces cell death in MM cell lines and primary samples in vitro, especially in t(11;14)-positive (pos) cells, which express a high ratio of BCL2 to MCL1(VEN resistance factor). The current Ph 1 study evaluates safety and efficacy of VEN in pts with R/R MM. Methods: Primary objectives are to evaluate safety, PK, and RPTD; other objectives include preliminary efficacy and impact of chromosomal abnormalities. In dose-escalation cohorts, VEN was given PO daily at 300, 600, 900, or 1200 mg after a 2-week dose ramp-up. Pts were monitored for tumor lysis syndrome (TLS). Results: As of 12/19/2014, there were 28 pts with median age 65 (12/16 F/M); 9 ISS stage I, 11 stage II, 6 stage III. Median (range) prior therapies: 6 (1–13). 23 had prior bortezomib (15 refractory), 26 lenalidomide (12 refractory), and 13 au...