Multinational phase 3 study of first-line ibrutinib-venetoclax in chronic lymphocytic leukemia: long-term results from GLOW

Long-term efficacy and toxicity data are needed to inform optimal first-line treatment for individual patients with chronic lymphocytic leukemia (CLL). The multinational phase 3 GLOW study randomized older or comorbid patients 1:1 to first-line ibrutinib-venetoclax (n=106) or chlorambucil-obinutuzumab (n=105). Long-term results have now been published. Sixty-six month overall survival (OS) rates were 79.0% with ibrutinib-venetoclax and 60.8% with chlorambucil-obinutuzumab (HR 0.46). Ibrutinib-venetoclax reduced the risk of requiring second-line therapy by by 77.4% and continued to improve progression-free survival (PFS) versus chlorambucil-obinutuzumab (66-months rates 51.7% versus 18.1%; HR 0.27), regardless of IGHV/MRD status. Ibrutinib-venetoclax-treated patients with undetectable MRD at end-of-treatment had better PFS outcomes than those wth detectable MRD, especially in patients with unmutated IGHV. Grade 3-4 treatment-emergent adverse event-free PFS was 51.6 months with ibrutinib-venetoclax and 30.2 months with chlorambucil-obinutuzumab. The authors conclude that first-line ibrutinib-venetoclax results in superior outcomes compared with chlorambucil-obinutuzumab for CLL in older or comorbid patients (graphical abstract).