BACKGROUND: New treatments have improved outcomes for @entity1 with relapsed @entity1072 ( @entity1072 ), but complete remissions remain uncommon. Venetoclax has a distinct mechanism of action; it targets @entity588 , a protein central to the survival of @entity1072 cells. METHODS: We conducted a phase 1 dose-escalation study of daily oral venetoclax in @entity1 with relapsed or @entity1072 or @entity1072 ( @entity1072 ) to assess safety, pharmacokinetic profile, and efficacy. In the dose-escalation phase, 56 @entity1 received active treatment in one of eight dose groups that ranged from 150 to 1200 mg per day. In an expansion cohort, 60 additional @entity1 were treated with a weekly stepwise ramp-up in doses as high as 400 mg per day. RESULTS: The majority of the study @entity1 had received multiple previous treatments, and 89% had poor prognostic clinical or genetic features. Venetoclax was active at all dose levels. Clinical @entity5405 occurred in 3 of 56 @entity1 in the dose-escalation cohort, with one @entity204 . After adjustments to the dose-escalation schedule, clinical @entity5405 did not occur in any of the 60 @entity1 in the expansion cohort. Other toxic effects included mild @entity294 (in 52% of the @entity1 ), @entity1729 (in 48%), @entity390 (in 47%), and grade 3 or 4 @entity1398 (in 41%). A maximum tolerated dose was not identified. Among the 116 @entity1 who received venetoclax, 92 (79%) had a response. Response rates ranged from 71 to 79% among @entity1 in subgroups with an adverse prognosis, including those with resistance to @entity3118 , those with chromosome 17p deletions (deletion 17p @entity1072 ), and those with unmutated @entity7513 . Complete remissions occurred in 20% of the @entity1 , including 5% who had no minimal residual disease on flow cytometry. The 15-month progression-free survival estimate for the 400-mg dose groups was 69%. CONCLUSIONS: Selective targeting of @entity588 with venetoclax had a manageable safety profile and induced substantial responses in @entity1 with relapsed @entity1072 or @entity1072 , including those with poor prognostic features. (Funded by AbbVie and Genentech; ClinicalTrials.gov number, NCT01328626.).

Targeting @entity588 with Venetoclax in Relapsed XXXX .

@entity1 :: ('9606', 'Species') :: ['patients'] @entity5405 :: ('MESH:D015275', 'Disease') :: ['tumor lysis syndrome'] @entity390 :: ('MESH:D009325', 'Disease') :: ['nausea'] @entity588 :: ('596', 'Gene') :: ['BCL2'] @entity294 :: ('MESH:D003967', 'Disease') :: ['diarrhea'] @entity1072 :: ('MESH:D015451', 'Disease') :: ['CLL', 'small lymphocytic lymphoma', 'SLL', 'chronic lymphocytic leukemia', 'refractory CLL'] @entity3118 :: ('MESH:C024352', 'Chemical') :: ['fludarabine'] @entity1398 :: ('MESH:D009503', 'Disease') :: ['neutropenia'] @entity1729 :: ('MESH:D012141', 'Disease') :: ['upper respiratory tract infection'] @entity204 :: ('MESH:D003643', 'Disease') :: ['death'] @entity7513 :: ('3492', 'Gene') :: ['IGHV']
@entity1072 :: (MESH:D015451,Disease) :: ['Chronic Lymphocytic Leukemia']
