Impact of Minimal Residual Disease on Progression-Free Survival Outcomes After Fixed-Duration Ibrutinib-Venetoclax Versus Chlorambucil-Obinutuzumab in the GLOW Study

作者：Talha Munir, Carol Moreno, Carolyn Owen, George Follows, Ohad Benjamini, Ann Janssens, Mark‐David Levin, Anders Österborg, Tadeusz Robak, Martin Šimkovič, Don A. Stevens, Sergey Voloshin, Vladimir Vorobyev, Münci Yağcı, Loïc Ysebaert, Keqin Qi, Qianya Qi, Lori Parisi, Srimathi Srinivasan, Natasha Schuier, Kurt Baeten, Angela Howes, Donne Bennett Caces, Carsten Utoft Niemann, Arnon P. Kater · 发表于：Journal of Clinical Oncology · 年份：2023 · DOI：10.1200/jco.22.02283 · 被引用次数：45 · 研究领域：Chronic Lymphocytic Leukemia Research、Immunodeficiency and Autoimmune Disorders、Phagocytosis and Immune Regulation

PURPOSE In GLOW, fixed-duration ibrutinib + venetoclax showed superior progression-free survival (PFS) versus chlorambucil + obinutuzumab in older/comorbid patients with previously untreated chronic lymphocytic leukemia (CLL). The current analysis describes minimal residual disease (MRD) kinetics and any potential predictive value for PFS, as it has not yet been evaluated for ibrutinib + venetoclax treatment. METHODS Undetectable MRD (uMRD) was assessed by next-generation sequencing at <1 CLL cell per 10,000 (<10−4) and <1 CLL cell per 100,000 (<10−5) leukocytes. PFS was analyzed by MRD status at 3 months after treatment (EOT+3). RESULTS Ibrutinib + venetoclax achieved deeper uMRD (<10−5) rates in bone marrow (BM) and peripheral blood (PB), respectively, in 40.6% and 43.4% of patients at EOT+3 versus 7.6% and 18.1% of patients receiving chlorambucil + obinutuzumab. Of these patients, uMRD (<10−5) in PB was sustained during the first year post-treatment (EOT+12) in 80.4% of patients receiving ibrutinib + venetoclax and 26.3% receiving chlorambucil + obinutuzumab. Patients with detectable MRD (dMRD; ≥10−4) in PB at EOT+3 were more likely to sustain MRD levels through EOT+12 with ibrutinib + venetoclax versus chlorambucil + obinutuzumab. PFS rates at EOT+12 were high among patients treated with ibrutinib + venetoclax regardless of MRD status at EOT+3: 96.3% and 93.3% in patients with uMRD (<10−4) and dMRD (≥10−4) in BM, respectively, versus 83.3% and 58.7% for patients receiving...