MEETING NEWS LYMPHOMA
Early-Phase Study Finds Venetoclax Plus Obinutuzumab Safe and Effective in Patients with Untreated CLL
Venetoclax – a highly selective , potent BCL2 inhibitor – demonstrated significant anti-tumor activity in patients with chronic lymphocytic leukemia ( CLL ), both as monotherapy and in combination with obinutuzumab , in preliminary results from a phase Ib study . Ian W . Flinn , MD , PhD , from the Sarah Cannon Center for Blood Cancer in Nashville , Tennessee , and co-authors reported updated safety , efficacy , and minimal residual disease ( MRD ) negativity data in patients with previously treated CLL at the 2017 ASH Annual Meeting .
“ This combination of venetoclax and obinutuzumab achieved high overall and complete remission rates ,” Dr . Flinn said during his presentation . This included “ high rates of undetectable bone marrow ( BM ) MRD , irrespective of response status .”
The trial enrolled patients with previously treated CLL ; patients were eligible if they had an Eastern Cooperative Oncology Group performance status score of ≤1 and adequate organ function .
Treatment was administered by one of two schedules during the first cycle : In schedule A , patients received venetoclax first ; in schedule B , patients received obinutuzumab first .
The recommended target dose for the safety-expansion cohorts was venetoclax 400 mg , which was determined from an earlier dose-finding cohort . Obinutuzumab was administered according to the approved dosing schedule ( cycle 1 : 100 mg on day 1 , 900 mg on day 2 , 1,000 mg on days 8 and 15 ; cycle 2-6 : 1,000 mg on day 1 , based on a 28-day cycle ).
Thirty-two patients ( median age = 63 years ; range not provided ) received six cycles of venetoclax plus obinutuzumab , followed by an additional six cycles of venetoclax alone . Depending on CLL disease status , venetoclax could be extended after one year of treatment .
The primary endpoints were safety and tolerability of venetoclax plus obinutuzumab , as well as efficacy and MRD negativity .
During the first cycle of treatment , six patients received schedule A and 26 received schedule B . All 32 patients completed six cycles of venetoclax plus obinutuzumab ; follow-up continued for at least nine months from treatment onset . Twelve patients were followed for longer than 15 months .
Median time on study was 11.3 months ( range not provided ). All patients experienced at least one adverse event ( AE ); the most commonly reported AEs were neutropenia , febrile neutropenia , and thrombocytopenia . No cases of tumor lysis syndrome were reported on either schedule , and there were no treatment discontinuations related to AEs . There were no deaths as of data cutoff ( date not reported ).
All 32 patients in the study responded to treatment ( overall response rate = 100 %), including 17 patients with complete response ( CR ), one with CR with incomplete hematologic recovery ( 56.3 %), and 14 with partial response ( 43.8 %).
The rate of progression-free survival at one year was 100 percent . At 437 and 451 days after treatment initiation , two patients ( 6.3 %) had disease progression , both of whom had del17p mutation at screening .
MRD negativity in peripheral blood occurred in all participants , and 20 patients ( 62.5 % in intention-to-treat population ; 74 % in patients with samples available ) achieved MRD negativity in BM .
Dr . Flinn called the rates of MRD negativity “ unprecedented ,” compared with other chemo-immunotherapy regimens or chemotherapy-free approaches . These results suggest “ that [ venetoclax plus obinutuzumab ] may be administered with a favorable benefit-risk profile ,” the authors concluded .
This combination is being tested in a phase III trial , and Dr . Flinn noted that questions remain about the optimal venetoclax-based combination . ●
The authors report financial relationships with Roche , AbbVie , and Genentech .
REFERENCE
Flinn IW , Gribben JG , Dyer MJS , et al . Safety , efficacy and MRD negativity of a combination of venetoclax and obinutuzumab in patients with previously untreated chronic lymphocytic leukemia — results from a phase 1b study ( GP28331 ). Abstract # 430 . Presented at the 2017 ASH Annual Meeting , December 10 , 2017 ; Atlanta , GA .
SCENES FROM THE 2017 ASH ANNUAL MEETING
18 Focus on Lymphoma & Myeloma