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

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.

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Journal
Blood
Published
2025-02-26
DOI
https://doi.org/10.1182/blood.2024025525
Citations
31
Primary Topic
Chronic Lymphocytic Leukemia Research
Type
article
Field-Weighted Citation Impact
50.39

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article

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

Rosemary Millen, Nicole Lamanna, Rosemary Anne Harrup, Yanwen Jiang et al.
31 citations
Blood
Chronic Lymphocytic Leukemia Research
50.39
article

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

Rosemary Millen, Nicole Lamanna, Rosemary Anne Harrup, Yanwen Jiang, Clemens Mellink, Guillaume Cartron, Thomas J. Kipps, Ulrich Jäger, Marco Montillo, Relja Popovic, Carolyn Owen, Maria Thadani‐Mulero, Arnon Philip Kater, Brenda Chyla, Sarit Assouline, Anton W. Langerak, Michelle Boyer, John Francis Seymour, Javier de la Serna, Marcus Lefebure, Tadeusz Robak, Barbara F. Eichhorst
article en
31 citations

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.

BloodVol. 145(23)
TH Köln - University of Applied Sciences (DE), The Royal Melbourne Hospital (AU), Amgen (United States) (US), University of San Diego (US), University of Calgary (CA), University of Cologne (DE), Columbia University Irving Medical Center (US), Peter MacCallum Cancer Centre (AU), Jewish General Hospital (CA), Erasmus MC (NL), Amsterdam UMC Location University of Amsterdam (NL), Royal Hobart Hospital (AU), AbbVie (United States) (US), University of California San Diego (US), Research Institute Hospital 12 de Octubre (ES), Centre Hospitalier Universitaire de Montpellier (FR), Azienda Socio Sanitaria Territoriale Grande Ospedale Metropolitano Niguarda (IT), Hospital Universitario 12 De Octubre (ES), Occupational Cancer Research Centre (CA), Roche (United Kingdom) (GB), Medical University of Lodz (PL), Amsterdam University Medical Centers (NL), Medical University of Vienna (AT), Erasmus University Rotterdam (NL)
F. Hoffmann-La Roche, Genentech
Good health and well-being
Openalex Percentile: Top 0%
Chronic Lymphocytic Leukemia Research
50.39
DOIOpen Access PDFOpenAlex
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