Infection and Prophylaxis With Venetoclax Plus Obinutuzumab in CLL14

Danielle M. Brander, MD, of Duke University School of Medicine, summarizes the CLL14 trial in chronic lymphocytic leukemia (CLL), which randomized patients to chlorambucil plus obinutuzumab or fixed-duration venetoclax plus obinutuzumab given for about 12 months. Final results at EHA 2026, at a median observation of about 110 months, showed durable progression-free survival, while in the primary analysis grade 3 or 4 infection occurred in 17.5% of patients on venetoclax plus obinutuzumab versus 15% on chlorambucil plus obinutuzumab. Marc J. Braunstein, MD, PhD, of NYU Grossman Long Island School of Medicine, suspects many CLL14 infections were driven by obinutuzumab, recalling efforts to avoid anti-CD20 antibodies during the COVID-19 pandemic. Before starting the regimen, he reviews vaccination history and checks hepatitis B and C given reactivation risk with obinutuzumab. During treatment he counsels vigilance about reporting infections, maintains close surveillance, and would consider intravenous immunoglobulin for a patient with infection and reduced IgG.