{"entity":{"id":"paper-roberts-venetoclax-relapsed-cll-nejm-2016","kind":"paper","name":"Targeting BCL2 with venetoclax in relapsed chronic lymphocytic leukemia","aka":[],"tldr":"The first-in-human study of venetoclax, the BCL-2 blocker that grew from a discovery at the Walter and Eliza Hall Institute in Melbourne. Four in five people with relapsed CLL responded.","summary":"A phase 1 dose-escalation study (NCT01328626) of daily oral venetoclax in relapsed or refractory chronic lymphocytic leukaemia or small lymphocytic lymphoma, led from the Royal Melbourne Hospital, the Walter and Eliza Hall Institute and Peter MacCallum Cancer Centre with AbbVie and Genentech. 56 patients received one of eight doses from 150 to 1,200 mg a day; 60 more were treated in an expansion cohort with a weekly stepwise ramp-up to 400 mg. Most had several previous treatments and 89 percent had poor prognostic clinical or genetic features.\n\nClinical tumour lysis syndrome occurred in 3 of 56 patients in dose escalation, with one death; after the ramp-up schedule was introduced it occurred in none of the 60 in the expansion cohort. 92 of 116 patients (79 percent) responded, including 71 to 79 percent in subgroups with fludarabine resistance, 17p deletion or unmutated IGHV; 20 percent had complete remission, 5 percent without minimal residual disease by flow cytometry. Estimated 15-month progression-free survival at 400 mg was 69 percent.","asOf":"2026-11-03","links":[{"label":"NEJM 2016","url":"https://doi.org/10.1056/NEJMoa1513257"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/26639348/"}],"tags":[],"related":[],"cancers":["cll"],"sections":["targeted-therapy"],"technologies":[],"targets":[],"drugs":["venetoclax"],"companies":[],"institutions":["wehi","peter-mac"],"pathways":[],"terms":[],"trials":["murano"],"people":["andrew-roberts","john-seymour"],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"journal":"New England Journal of Medicine","year":2016,"doi":"10.1056/NEJMoa1513257","pmid":"26639348","authors":"Roberts AW, Davids MS, Pagel JM, Kahl BS, Puvvada SD, Gerecitano JF, Kipps TJ, Anderson MA, Brown JR, Gressick L, Wong S, Dunbar M, Zhu M, Desai MB, Cerri E, Heitner Enschede S, Humerickhouse RA, Wierda WG, Seymour JF","paperType":"translational","findings":["Response in 92 of 116 patients (79%); 71% to 79% in fludarabine-resistant, 17p-deleted and IGHV-unmutated subgroups.","Complete remission in 20%, including 5% with no minimal residual disease by flow cytometry.","Clinical tumour lysis syndrome in 3 of 56 in dose escalation (one death), none of 60 after the weekly ramp-up.","No maximum tolerated dose identified; 15-month progression-free survival estimate 69% at 400 mg."],"whatItMeans":"It showed that blocking BCL-2 could clear chronic lymphocytic leukaemia that other drugs had not, and the ramp-up dosing it introduced to prevent tumour lysis is still how venetoclax is started.","caveats":["Phase 1 and single-arm; the randomised evidence came later, in MURANO and CLL14.","Funded by AbbVie and Genentech, with company employees among the authors."],"participants":116},"route":"/key-papers/paper-roberts-venetoclax-relapsed-cll-nejm-2016/","neighbours":{"cancer":[{"id":"cll","kind":"cancer","name":"Chronic lymphocytic leukaemia","route":"/cancers/cll/"}],"section":[{"id":"targeted-therapy","kind":"section","name":"Targeted Therapy","route":"/fronts/targeted-therapy/"}],"drug":[{"id":"venetoclax","kind":"drug","name":"Venetoclax","route":"/drugs/venetoclax/"}],"institution":[{"id":"peter-mac","kind":"institution","name":"Peter MacCallum Cancer Centre","route":"/institutions/peter-mac/"},{"id":"wehi","kind":"institution","name":"Walter and Eliza Hall Institute of Medical Research","route":"/institutions/wehi/"}],"trial":[{"id":"murano","kind":"trial","name":"MURANO","route":"/trials/murano/"}],"person":[{"id":"andrew-roberts","kind":"person","name":"Andrew Roberts","route":"/people/andrew-roberts/"},{"id":"john-seymour","kind":"person","name":"John F. Seymour","route":"/people/john-seymour/"}]}}