The MURANO study: final analysis and retreatment/crossover substudy results of VenR for patients with relapsed/refractory CLL

作者：Arnon P. Kater, Rosemary Harrup, Thomas J. Kipps, Barbara Eichhorst, Carolyn Owen, Sarit Assouline, Nicole Lamanna, Tadeusz Robak, Javier de la Serna, Ulrich Jäger, Guillaume Cartron, Marco Montillo, Clemens Mellink, Anton W. Langerak, Brenda Chyla, Relja Popovic, Yanwen Jiang, Rosemary Millen, Marcus Lefebure, Maria Thadani‐Mulero, Michelle Boyer, John F. Seymour · 发表于：Blood · 年份：2025 · DOI：10.1182/blood.2024025525 · 被引用次数：57 · 研究领域：Chronic Lymphocytic Leukemia Research、Advanced Breast Cancer Therapies、Diabetes Treatment and Management

ABSTRACT: Fixed-duration venetoclax-rituximab (VenR) in patients with relapsed/refractory chronic lymphocytic leukemia (CLL) in the phase 3 MURANO trial resulted in superior progression-free survival (PFS) and overall survival (OS) vs bendamustine-rituximab (BR). We report the final analyses of MURANO (median follow-up, 7 years). Patients were randomized to VenR (venetoclax 400 mg daily for 2 years plus monthly rituximab for 6 months; n = 194) or BR (6 months; n = 195). In a substudy, patients with progressive disease (PD) received VenR as retreatment or crossover from BR. At the final data cut (3 August 2022), the median PFS with VenR was 54.7 months vs 17.0 months with BR. The 7-year PFS with VenR was 23.0%. The 7-year OS was 69.6% and 51.0%, respectively. Among VenR-treated patients with undetectable minimal residual disease (MRD; uMRD) and no PD at end of treatment (EOT; n = 83), the median PFS from EOT was 52.5 vs 18.0 months in patients with MRD at EOT (n = 35; P < .0001). Fourteen patients had enduring uMRD. Three distinct mutations in BCL2 in 4 patients were identified. In the substudy, 25 patients were retreated with VenR, and 9 patients crossed over to VenR; the median PFS was 23 and 27 months, and the best overall response rate was 72% and 89%, respectively. At the end of combination treatment (EOCT), after retreatment or crossover, 8 and 6 patients achieved uMRD, respectively. No new safety findings were observed. Overall, these final MURANO analyses support consi...