{"entity":{"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","aka":[],"tldr":"A fixed one-year course of two targeted drugs kept CLL under control far longer than chemo-immunotherapy, and most patients had no detectable disease when treatment stopped.","summary":"CLL14 randomised 432 previously untreated patients with CLL and coexisting conditions (CIRS score above 6 or creatinine clearance under 70 mL/min) to 12 cycles of venetoclax plus obinutuzumab or chlorambucil plus obinutuzumab. The primary endpoint was investigator-assessed progression-free survival. At 24 months PFS was 88.2% versus 64.1% (hazard ratio 0.35), and undetectable MRD in peripheral blood three months after treatment ended was 75.5% versus 35.2%. Grade 3-4 neutropenia and infections were similar between arms. With six years of follow-up more than half of venetoclax-obinutuzumab patients remained progression-free against roughly a fifth on chemo-immunotherapy, though overall survival was not significantly different.","asOf":"2026-09-08","links":[{"label":"Full text (DOI)","url":"https://doi.org/10.1056/NEJMoa1815281"},{"label":"ClinicalTrials.gov NCT02242942","url":"https://clinicaltrials.gov/study/NCT02242942"}],"tags":[],"related":["venetoclax-plus-obinutuzumab"],"cancers":["cll"],"sections":[],"technologies":[],"targets":["bcl2","cd20"],"drugs":["venetoclax","obinutuzumab"],"companies":["abbvie","roche-genentech"],"institutions":[],"pathways":[],"terms":["mrd","pfs","ighv-status","del17p-tp53"],"trials":["cll14","cll13-gaia"],"people":["michael-hallek"],"bottlenecks":["b-dormancy-mrd","b-aging-comorbidity"],"keyPapers":[],"journals":["nejm"],"dependsOn":[],"notes":[],"journal":"New England Journal of Medicine","year":2019,"doi":"10.1056/NEJMoa1815281","authors":"Fischer K, Al-Sawaf O, Bahlo J, et al.","paperType":"rct","findings":["432 patients with untreated CLL and comorbidities; 12 cycles of venetoclax-obinutuzumab vs chlorambucil-obinutuzumab.","24-month PFS 88.2% vs 64.1%; hazard ratio 0.35.","Undetectable MRD (below 10^-4) in blood 3 months after treatment end: 75.5% vs 35.2%.","Grade 3-4 neutropenia 52.8% vs 48.1%; grade 3-4 infections 17.5% vs 15.0%.","Benefit held across IGHV-unmutated and TP53-aberrant subgroups, though del(17p)/TP53 patients relapsed earlier."],"whatItMeans":"CLL14 established the first chemotherapy-free, fixed-duration regimen for front-line CLL and made MRD-guided thinking mainstream in the disease. Patients get a year of treatment and then a treatment-free period rather than indefinite therapy. The choice today is between fixed-duration venetoclax combinations and continuous BTK inhibitors, with no proven survival difference.","caveats":["Overall survival has not differed significantly, partly because effective salvage therapies exist.","Patients were older and less fit; CLL13/GAIA later confirmed benefit in fit patients.","Venetoclax requires a 5-week ramp-up and tumour-lysis monitoring, which is a practical burden.","Retreatment strategy after relapse was not defined by the trial."],"changedPractice":true,"participants":432},"route":"/key-papers/paper-cll14-venetoclax-obinutuzumab-nejm-2019/","neighbours":{"pairing":[{"id":"venetoclax-plus-obinutuzumab","kind":"pairing","name":"Venetoclax + obinutuzumab (12 months)","route":"/pairings/venetoclax-plus-obinutuzumab/"}],"cancer":[{"id":"cll","kind":"cancer","name":"Chronic lymphocytic leukaemia","route":"/cancers/cll/"},{"id":"cll-treatment-naive","kind":"cancer","name":"Chronic lymphocytic leukaemia, first treatment","route":"/cancers/cll-treatment-naive/"}],"target":[{"id":"bcl2","kind":"target","name":"BCL-2","route":"/targets/bcl2/"},{"id":"cd20","kind":"target","name":"CD20","route":"/targets/cd20/"}],"drug":[{"id":"obinutuzumab","kind":"drug","name":"Obinutuzumab","route":"/drugs/obinutuzumab/"},{"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":"ighv-status","kind":"term","name":"IGHV mutational status","route":"/terms/ighv-status/"},{"id":"mrd","kind":"term","name":"Minimal / molecular residual disease (MRD)","route":"/terms/mrd/"},{"id":"pfs","kind":"term","name":"Progression-free survival (PFS)","route":"/terms/pfs/"}],"trial":[{"id":"cll13-gaia","kind":"trial","name":"CLL13 / GAIA","route":"/trials/cll13-gaia/"},{"id":"cll14","kind":"trial","name":"CLL14","route":"/trials/cll14/"}],"person":[{"id":"kirsten-fischer","kind":"person","name":"Kirsten Fischer","route":"/people/kirsten-fischer/"},{"id":"michael-hallek","kind":"person","name":"Michael Hallek","route":"/people/michael-hallek/"}],"bottleneck":[{"id":"b-dormancy-mrd","kind":"bottleneck","name":"Dormant cells and minimal residual disease","route":"/bottlenecks/b-dormancy-mrd/"},{"id":"b-aging-comorbidity","kind":"bottleneck","name":"Older and multimorbid patients are excluded and undertreated","route":"/bottlenecks/b-aging-comorbidity/"}],"journal":[{"id":"nejm","kind":"journal","name":"New England Journal of Medicine","route":"/journals/nejm/"}],"paper":[{"id":"paper-murano-venetoclax-rituximab-nejm-2018","kind":"paper","name":"MURANO: two years of venetoclax plus rituximab versus chemo-immunotherapy in relapsed CLL","route":"/key-papers/paper-murano-venetoclax-rituximab-nejm-2018/"}]}}