CLL14: Venetoclax-obinutuzumab in previously untreated CLL

Final analysis results from the randomized phase III CLL14 study (NCT02242942), evaluating fixed-duration venetoclax + obinutuzumab (Ven + Obi; n = 216) vs chlorambucil + obinutuzumab (Clb + Obi; n = 216) in previously untreated patients with chronic lymphocytic leukemia (CLL) and coexisting medical conditions, were presented by Kirsten Fischer at the European Hematology Association (EHA) 2026 Congress, June 11–14, 2026, Stockholm, SE. The primary endpoint was progression-free survival (PFS). 

Key data: At a median observation time of 110.1 months, Ven + Obi demonstrated a median PFS of 76.6 months vs 37.9 months with Clb + Obi (hazard ratio [HR], 0.50; 95% confidence interval [CI], 0.39–0.63; p < 0.001). Median time-to-next treatment (TTNT) was 91.9 vs 52.5 months (HR, 0.54; 95% CI, 0.43–0.70; p < 0.0001). Median overall survival (OS) was not reached with Ven + Obi vs 112.7 months with Clb + Obi (HR, 0.80; 95% CI, 0.59–1.09; p = 0.161). End-of-treatment measurable residual disease (MRD) status remained prognostic for both PFS and OS. A higher incidence of second primary malignancies (SPMs) was observed with Ven + Obi vs Clb + Obi (2.6 vs 1.5 per 1,000 patient-months; p = 0.047).

Key learning: One-year fixed-duration Ven + Obi achieves durable long-term efficacy in previously untreated patients with CLL. The increased incidence of SPMs in the Ven + Obi arm warrants ongoing monitoring in long-term follow-up.