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

Kater, AP; Harrup, R; Owen, CJ; Kipps, TJ; Assouline, S; Eichhorst, B; Lamanna, N; Robak, T; de la Serna, J; Jaeger, U; Cartron, G; Montillo, M; Mellink, C; Langerak, AW; Chyla, B; Popovic, R; Jiang, Y; Millen, R; Lefebure, M; Thadani-Mulero, M; Boyer, M; Seymour, JF

Author(s): Kater, AP; Harrup, R; Owen, CJ; Kipps, TJ; Assouline, S; Eichhorst, B; Lamanna, N; Robak, T; de la Serna, J; Jaeger, U; Cartron, G; Montillo, M; Mellink, C; Langerak, AW; Chyla, B; Popovic, R; Jiang, Y; Millen, R; Lefebure, M; Thadani-Mulero, M; Boyer, M; Seymour, JF;
Details: Publication Year 2025-06-05,Volume 145,Issue #23,Page 2733-2745
Journal Title: Blood
Publication Type: Research article
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 consideration of fixed-duration VenR therapy for patients with relapsed/refractory CLL. This trial was registered at www.clinicaltrials.gov as #NCT02005471.
Publisher: American Society of Hematology
Keywords: Humans; *Leukemia, Lymphocytic, Chronic, B-Cell/drug therapy/mortality/pathology/genetics; Male; Female; Aged; Middle Aged; Cross-Over Studies; *Antineoplastic Combined Chemotherapy Protocols/therapeutic use/adverse effects; *Rituximab/administration & dosage/therapeutic use/adverse effects; Bridged Bicyclo Compounds, Heterocyclic/administration & dosage/therapeutic; use/adverse effects; Sulfonamides/administration & dosage/therapeutic use/adverse effects; Aged, 80 and over; Retreatment; *Neoplasm Recurrence, Local/drug therapy; Adult; Bendamustine Hydrochloride/administration & dosage
Department(s): Haematology
Publisher's Version: https://doi.org/10.1182/blood.2024025525
Terms of Use/Rights Notice: Refer to copyright notice on published article.

Creation Date: 2025-03-21 02:49:40

Last Modified: 2025-07-31 02:10:13