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.
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not linked directly; found by shared links- Key paperAMPLIFY: fixed-duration acalabrutinib plus venetoclax, with or without obinutuzumab, versus chemo-immunotherapy in fit CLL patients
Shares del(17p) / TP53 aberration in CLL, AbbVie (incl. ImmunoGen, Capstan), CD20, BCL-2.
- PairingVenetoclax + obinutuzumab (12 months)
Shares CLL14: one year of venetoclax plus obinutuzumab instead of chemo-immunotherapy in older, less fit CLL patients, CD20, BCL-2, Venetoclax.
- PairingCaution: chemoimmunotherapy in del(17p)/TP53 CLL
Shares del(17p) / TP53 aberration in CLL, Rituximab, Venetoclax, Chronic lymphocytic leukaemia.
- TrialCLL13 / GAIA
Shares CLL14: one year of venetoclax plus obinutuzumab instead of chemo-immunotherapy in older, less fit CLL patients, Rituximab, CD20, BCL-2.
- TrialAMPLIFY
Shares del(17p) / TP53 aberration in CLL, CD20, BCL-2, Venetoclax.
- InstitutionWalter and Eliza Hall Institute of Medical Research
Shares AbbVie (incl. ImmunoGen, Capstan), BCL-2, Venetoclax, Roche / Genentech.
- TrialCLL14
Shares CLL14: one year of venetoclax plus obinutuzumab instead of chemo-immunotherapy in older, less fit CLL patients, CD20, BCL-2, Venetoclax.
- PersonMichael Hallek
Shares CLL14: one year of venetoclax plus obinutuzumab instead of chemo-immunotherapy in older, less fit CLL patients, CD20, BCL-2, Venetoclax.