# MURANO: two years of venetoclax plus rituximab versus chemo-immunotherapy in relapsed CLL

Source: https://onco.cc/key-papers/paper-murano-venetoclax-rituximab-nejm-2018/  
OnCo record `paper-murano-venetoclax-rituximab-nejm-2018` (Key paper). Data CC BY-NC 4.0, attribute "Data from OnCo (onco.cc)"; commercial use needs a licence.

## TL;DR

In relapsed CLL, a time-limited venetoclax-rituximab course cut progression risk by more than 80% compared with bendamustine-rituximab and later improved survival.

## Summary

MURANO randomised 389 patients with relapsed or refractory CLL to venetoclax for two years plus six months of rituximab, or six cycles of bendamustine-rituximab. The primary endpoint was investigator-assessed PFS. At 24 months PFS was 84.9% versus 36.3% (hazard ratio 0.17), with benefit across del(17p) and other high-risk subgroups. Rates of undetectable MRD were much higher with venetoclax-rituximab. With five years of follow-up the overall survival advantage held (about 82% versus 62%), and most patients who reached undetectable MRD at end of therapy stayed in remission for years off treatment.

## Fields

- Kind: Key paper
- Last checked: 2026-09-08
- Journal: New England Journal of Medicine
- Year: 2018
- DOI: 10.1056/NEJMoa1713976
- Authors: Seymour JF, Kipps TJ, Eichhorst B, et al.
- Findings: 389 patients with relapsed/refractory CLL; venetoclax (2 years) + rituximab vs bendamustine-rituximab.; 24-month PFS 84.9% vs 36.3%; hazard ratio 0.17.; Benefit preserved in del(17p), TP53-mutated and IGHV-unmutated disease.; Peripheral-blood undetectable MRD at end of combination treatment was far more frequent with venetoclax-rituximab.; Five-year overall survival roughly 82% vs 62%; end-of-treatment MRD status predicted subsequent PFS.
- What it means: MURANO made fixed-duration venetoclax the standard for relapsed CLL and showed that stopping therapy after a deep response is safe for most patients. It also established MRD at end of treatment as a practical guide to who is likely to stay in remission. Retreatment with venetoclax at relapse appears feasible.
- Caveats: Bendamustine-rituximab is a weak comparator by today's standards; there is no head-to-head against BTK inhibitors in this setting.; Few patients had prior BTK inhibitor exposure, so results may not apply after BTKi failure.; Open-label design with investigator-assessed endpoints.; Tumour-lysis prophylaxis and ramp-up add complexity.

## Sources

- Full text (DOI): https://doi.org/10.1056/NEJMoa1713976
- ClinicalTrials.gov NCT02005471: https://clinicaltrials.gov/study/NCT02005471

## Connected records

- key papers: [CLL14: one year of venetoclax plus obinutuzumab instead of chemo-immunotherapy in older, less fit CLL patients](https://onco.cc/key-papers/paper-cll14-venetoclax-obinutuzumab-nejm-2019/)
- cancers: [Chronic lymphocytic leukaemia](https://onco.cc/cancers/cll/), [Relapsed or refractory chronic lymphocytic leukaemia](https://onco.cc/cancers/cll-relapsed/)
- targets: [BCL-2](https://onco.cc/targets/bcl2/), [CD20](https://onco.cc/targets/cd20/)
- drugs: [Bendamustine](https://onco.cc/drugs/bendamustine/), [Rituximab](https://onco.cc/drugs/rituximab/), [Venetoclax](https://onco.cc/drugs/venetoclax/)
- companies: [AbbVie (incl. ImmunoGen, Capstan)](https://onco.cc/companies/abbvie/), [Roche / Genentech](https://onco.cc/companies/roche-genentech/)
- terms: [del(17p) / TP53 aberration in CLL](https://onco.cc/terms/del17p-tp53/), [Minimal / molecular residual disease (MRD)](https://onco.cc/terms/mrd/), [Overall survival (OS)](https://onco.cc/terms/os/), [Progression-free survival (PFS)](https://onco.cc/terms/pfs/)
- bottlenecks: [Acquired resistance to every therapy](https://onco.cc/bottlenecks/b-resistance/), [Dormant cells and minimal residual disease](https://onco.cc/bottlenecks/b-dormancy-mrd/)
- journals: [New England Journal of Medicine](https://onco.cc/journals/nejm/)
- people: [John F. Seymour](https://onco.cc/people/john-seymour/)

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