{"entity":{"id":"paper-murano-venetoclax-rituximab-nejm-2018","kind":"paper","name":"MURANO: two years of venetoclax plus rituximab versus chemo-immunotherapy in relapsed CLL","aka":[],"tldr":"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.","asOf":"2026-09-08","links":[{"label":"Full text (DOI)","url":"https://doi.org/10.1056/NEJMoa1713976"},{"label":"ClinicalTrials.gov NCT02005471","url":"https://clinicaltrials.gov/study/NCT02005471"}],"tags":[],"related":["paper-cll14-venetoclax-obinutuzumab-nejm-2019"],"cancers":["cll"],"sections":[],"technologies":[],"targets":["bcl2","cd20"],"drugs":["venetoclax","rituximab","bendamustine"],"companies":["abbvie","roche-genentech"],"institutions":[],"pathways":[],"terms":["mrd","pfs","os","del17p-tp53"],"trials":[],"people":[],"bottlenecks":["b-dormancy-mrd","b-resistance"],"keyPapers":[],"journals":["nejm"],"dependsOn":[],"notes":[],"journal":"New England Journal of Medicine","year":2018,"doi":"10.1056/NEJMoa1713976","authors":"Seymour JF, Kipps TJ, Eichhorst B, et al.","paperType":"rct","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."],"whatItMeans":"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."],"changedPractice":true,"participants":389},"route":"/key-papers/paper-murano-venetoclax-rituximab-nejm-2018/","neighbours":{"paper":[{"id":"paper-cll14-venetoclax-obinutuzumab-nejm-2019","kind":"paper","name":"CLL14: one year of venetoclax plus obinutuzumab instead of chemo-immunotherapy in older, less fit CLL patients","route":"/key-papers/paper-cll14-venetoclax-obinutuzumab-nejm-2019/"}],"cancer":[{"id":"cll","kind":"cancer","name":"Chronic lymphocytic leukaemia","route":"/cancers/cll/"},{"id":"cll-relapsed","kind":"cancer","name":"Relapsed or refractory chronic lymphocytic leukaemia","route":"/cancers/cll-relapsed/"}],"target":[{"id":"bcl2","kind":"target","name":"BCL-2","route":"/targets/bcl2/"},{"id":"cd20","kind":"target","name":"CD20","route":"/targets/cd20/"}],"drug":[{"id":"bendamustine","kind":"drug","name":"Bendamustine","route":"/drugs/bendamustine/"},{"id":"rituximab","kind":"drug","name":"Rituximab","route":"/drugs/rituximab/"},{"id":"venetoclax","kind":"drug","name":"Venetoclax","route":"/drugs/venetoclax/"}],"company":[{"id":"abbvie","kind":"company","name":"AbbVie (incl. ImmunoGen, Capstan)","route":"/companies/abbvie/"},{"id":"roche-genentech","kind":"company","name":"Roche / Genentech","route":"/companies/roche-genentech/"}],"term":[{"id":"del17p-tp53","kind":"term","name":"del(17p) / TP53 aberration in CLL","route":"/terms/del17p-tp53/"},{"id":"mrd","kind":"term","name":"Minimal / molecular residual disease (MRD)","route":"/terms/mrd/"},{"id":"os","kind":"term","name":"Overall survival (OS)","route":"/terms/os/"},{"id":"pfs","kind":"term","name":"Progression-free survival (PFS)","route":"/terms/pfs/"}],"bottleneck":[{"id":"b-resistance","kind":"bottleneck","name":"Acquired resistance to every therapy","route":"/bottlenecks/b-resistance/"},{"id":"b-dormancy-mrd","kind":"bottleneck","name":"Dormant cells and minimal residual disease","route":"/bottlenecks/b-dormancy-mrd/"}],"journal":[{"id":"nejm","kind":"journal","name":"New England Journal of Medicine","route":"/journals/nejm/"}],"person":[{"id":"john-seymour","kind":"person","name":"John F. Seymour","route":"/people/john-seymour/"}]}}