EHA2021: Phase III GLOW Trial of Ibrutinib and Venetoclax as First-Line CLL Therapy
Posted: Monday, June 14, 2021
The all-oral and once-daily combination therapy consisting of fixed-duration ibrutinib plus venetoclax was superior to chlorambucil plus obinutuzumab as first-line treatment of patients with chronic lymphocytic leukemia (CLL), with improved depth and duration of remission. Arnon Kater, MD, PhD, of the University of Amsterdam, presented these results from the GLOW trial on behalf of his colleagues during the European Hematology Association Virtual Congress (EHA2021; Abstract LB1902).
This phase III trial enrolled 211 patients with CLL who had a Cumulative Illness Rating Scale (CIRS) score of greater than 6 or a creatinine clearance less than 70 mL/min (suitable for reduced treatment). Patients were randomly assigned 1:1 to receive either 3 cycles of 420 mg of daily ibrutinib, followed by 12 cycles of ibrutinib and 400 mg of daily venetoclax, or 6 cycles of standard-dose chlorambucil and obinutuzumab.
After a median follow-up of 27.7 months, progression-free survival was superior in the ibrutinib-plus-venetoclax group compared with standard therapy (hazard ratio = 0.216, P < .0001). The median progression-free survival was not reached in the experimental group, but it was 21 months for the chlorambucil-and-obinutuzumab group. At 3 months after the end of treatment, the rate of undetectable minimal residual disease (MRD) in the bone marrow was higher with ibrutinib/venetoclax (51.9%) compared with chlorambucil/obinutuzumab (17.1%). Within the experimental group, 84.5% of patients maintained peripheral blood undetectable MRD 12 months after therapy cessation. The complete response rates were 38.7% and 11.4% among the ibrutinib/venetoclax and chlorambucil/obinutuzumab cohorts, respectively.
The most common grade 3 or higher adverse events in the experimental group were neutropenia/decreased neutrophil count (34.9%), diarrhea (10.4%), and hypertension (7.5%), whereas neutropenia/decreased neutrophil count (49.5%), thrombocytopenia (20%), pneumonia (5.7%), and tumor-lysis syndrome (5.7%) were more common in the control group. Seven patients in the ibrutinib/venetoclax cohort and two patients in the chlorambucil/obinutuzumab cohort experienced grade 5 adverse events.
Disclosure: There was no disclosure information available with the abstract submission.