In an analysis of the phase III GLOW trial reported in the Journal of Clinical Oncology, Talha Munir, MBBS, and colleagues found that fixed-duration ibrutinib/venetoclax produced higher rates of undetectable measurable residual disease (MRD) vs chlorambucil/obinutuzumab in previously untreated patients with chronic lymphocytic leukemia (CLL) who were aged 65 or older and/or who had comorbidities. Progression-free survival rates were high in the ibrutinib/venetoclax group irrespective of MRD status.
Talha Munir, MBBS
Study Details
In the GLOW trial, 211 patients were randomly assigned to receive fixed-duration ibrutinib/venetoclax (n = 106) or chlorambucil/obinutuzumab (n = 105). Trial results showed superior progression-free survival with ibrutinib/venetoclax. In the current analysis, undetectable MRD was assessed at levels of < 10-4 and < 10-5, with progression-free survival at 12 months after treatment being analyzed by MRD status at 3 months after treatment.
Key Findings
At 3 months after the end of treatment, undetectable MRD at < 10-5 was observed in the bone marrow of 40.6% of patients in the ibrutinib/venetoclax group vs 7.6% of those in the chlorambucil/obinutuzumab group and in peripheral blood in 43.4% vs 18.1%. Among these patients, undetectable MRD at < 10-5 in peripheral blood was sustained at 12 months after the end of treatment in 80.4% vs 26.3%.
Patients with detectable MRD (≥ 10-4) in peripheral blood at 3 months after the end of treatment in the ibrutinib/venetoclax group were less likely to have increased levels of MRD at 12 months after the end of treatment vs the chlorambucil/obinutuzumab group.
Progression-free survival at 12 months after the end of treatment was high in the ibrutinib/venetoclax group regardless of MRD status at 3 months after the end of treatment. Rates were 96.3% vs 83.3% in the chlorambucil/obinutuzumab group for patients with undetectable MRD at < 10-4 and 93.3% vs 58.7% for patients with detectable MRD in bone marrow.
Progression-free survival at 12 months after the end of treatment was high in the ibrutinib/venetoclax group among patients with wild-type IGHV, independent of MRD status in bone marrow at 3 months after the end of treatment. Rates were 93.8% vs 62.5% in the chlorambucil/obinutuzumab group for patients with undetectable MRD at < 10-4 and 90.0% vs 38.7% for patients with detectable MRD.
The investigators concluded: “Molecular and clinical relapses were less frequent during the first year post-treatment with ibrutinib/venetoclax vs chlorambucil/obinutuzumab regardless of MRD status at [3 months after the end of treatment] and IGHV status. Even for patients not achieving undetectable MRD (<10-4), progression-free survival rates remained high with ibrutinib/venetoclax; this is a novel finding and requires additional follow-up to confirm its persistence over time.”
Dr. Munir, of St. James’s Hospital, Leeds, United Kingdom, is the corresponding author of the Journal of Clinical Oncology article.
Disclosure: The study was supported by Janssen Research & Development, LLC. For full disclosures of the study authors, visit ascopubs.org.
