MURANO: two years of venetoclax plus rituximab versus chemo-immunotherapy in relapsed CLL
In relapsed CLL, a time-limited venetoclax-rituximab course cut progression risk by more than 80% compared with bendamustine-rituximab and later improved survival.
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.
- 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.
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.
- 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.