Venetoclax-obinutuzumab for previously untreated chronic lymphocytic leukemia: 6-year results of the randomized phase 3 CLL14 study

作者：Othman Al‐Sawaf, Sandra Robrecht, Can Zhang, Stefano Olivieri, Yi Meng Chang, Anna‐Maria Fink, Eugen Tausch, Christof Schneider, Matthias Ritgen, Karl‐Anton Kreuzer, Liliya Sivcheva, Carsten Utoft Niemann, Anthony P. Schwarer, Javier Loscertales, Robert Weinkove, Dirk Strumberg, Allanah Kilfoyle, Beenish S. Manzoor, Dureshahwar Jawaid, Nnadozie Emechebe, Jacob Devine, Michelle Boyer, Eva Diana Runkel, Barbara Eichhorst, Stephan Stilgenbauer, Yanwen Jiang, Michael Hallek, Kirsten Fischer · 发表于：Blood · 年份：2024 · DOI：10.1182/blood.2024024631 · 被引用次数：145 · 研究领域：Chronic Lymphocytic Leukemia Research、Immunodeficiency and Autoimmune Disorders、Lymphoma Diagnosis and Treatment

ABSTRACT: In the CLL14 study, patients with previously untreated chronic lymphocytic leukemia (CLL) and coexisting conditions were randomized to 12 cycles of venetoclax-obinutuzumab (Ven-Obi, n = 216) or chlorambucil-obinutuzumab (Clb-Obi, n = 216). Progression-free survival (PFS) was the primary end point. Key secondary end points included time-to-next-treatment (TTNT), rates of undetectable minimal residual disease (uMRD), overall survival (OS), and rates of adverse events. Patient reported outcomes of time until definitive deterioration (TUDD) in quality of life (QoL) were analyzed. At a median observation time of 76.4 months, PFS remained superior for Ven-Obi compared with Clb-Obi (median, 76.2 vs 36.4 months; hazard ratio [HR], 0.40; 95% confidence interval [CI], 0.31-0.52; P < .0001). Likewise, TTNT was longer after Ven-Obi (6-year TTNT, 65.2% vs 37.1%; HR, 0.44; 95% CI, 0.33-0.58; P < .0001). In the Ven-Obi arm, presence of del(17p), unmutated immunoglobulin heavy-chain variable region, and lymph node size of ≥5 cm were independent prognostic factors for shorter PFS. The 6-year OS rate was 78.7% in the Ven-Obi and 69.2% in the Clb-Obi arm (HR, 0.69; 95% CI, 0.48-1.01; P = .052). A significantly longer TUDD in global health status/QoL was observed in the Ven-Obi than in the Clb-Obi arm (median, 82.1 vs 65.1 months; HR, 0.70; 95% CI, 0.51-0.97). Follow-up-adjusted second primary malignancies incidence rates were 2.3 and 1.4 per 1000 patient-months in the Ven-Obi and Clb-...