{"entity":{"id":"paper-elevate-tn-acalabrutinib-lancet-2020","kind":"paper","name":"ELEVATE-TN: acalabrutinib, alone or with obinutuzumab, against chemo-immunotherapy in untreated CLL","aka":[],"tldr":"In ELEVATE-TN, acalabrutinib, a second-generation BTK inhibitor, with or without an antibody, cut the risk of progression by 80-90% compared with chlorambucil-obinutuzumab in older or unfit patients with CLL.","summary":"ELEVATE-TN was a three-arm phase 3 trial of 535 treatment-naive patients aged 65 or older, or younger with comorbidities. Patients were randomised to acalabrutinib plus obinutuzumab, acalabrutinib monotherapy, or chlorambucil plus obinutuzumab; the primary endpoint was PFS for the combination versus chemo-immunotherapy. At a median follow-up of 28.3 months median PFS was not reached in either acalabrutinib arm versus 22.6 months with chemo-immunotherapy, with hazard ratios of 0.10 for the combination and 0.20 for monotherapy. Acalabrutinib caused less atrial fibrillation and bleeding than reported with ibrutinib, and the trial supported its front-line approval.","asOf":"2026-09-08","links":[{"label":"PubMed search","url":"https://pubmed.ncbi.nlm.nih.gov/?term=ELEVATE-TN%20acalabrutinib%20obinutuzumab%20chlorambucil%20Sharman%20Lancet%202020"},{"label":"ClinicalTrials.gov NCT02475681","url":"https://clinicaltrials.gov/study/NCT02475681"}],"tags":[],"related":[],"cancers":["cll"],"sections":[],"technologies":[],"targets":["btk","cd20"],"drugs":["acalabrutinib","obinutuzumab","ibrutinib","zanubrutinib"],"companies":["astrazeneca"],"institutions":[],"pathways":[],"terms":["pfs"],"trials":["elevate-tn","sequoia"],"people":[],"bottlenecks":["b-toxicity-qol","b-drug-pricing"],"keyPapers":[],"journals":["lancet"],"dependsOn":[],"notes":[],"journal":"The Lancet","year":2020,"doi":"10.1016/S0140-6736(20)30262-2","pmid":"32305093","authors":"Sharman JP, Egyed M, Jurczak W, et al.","paperType":"rct","findings":["535 patients; acalabrutinib + obinutuzumab (179), acalabrutinib (179), chlorambucil + obinutuzumab (177).","Median PFS not reached in both acalabrutinib arms vs 22.6 months; hazard ratio 0.10 (combination) and 0.20 (monotherapy).","Estimated 24-month PFS about 93% (combination), 87% (monotherapy) and 47% (chemo-immunotherapy).","Headache and diarrhoea were the commonest acalabrutinib adverse events; atrial fibrillation was uncommon.","Adding obinutuzumab to acalabrutinib improved PFS further in longer follow-up but was not the primary comparison."],"whatItMeans":"ELEVATE-TN put a more selective BTK inhibitor into first-line CLL and, with the head-to-head ELEVATE-RR trial, showed it is as effective as ibrutinib with fewer cardiac side effects. Continuous acalabrutinib became one of the two main front-line options alongside fixed-duration venetoclax combinations. The trade-off is indefinite therapy and cost versus a time-limited course.","caveats":["The comparator, chlorambucil-obinutuzumab, was already being superseded when the trial reported.","Continuous therapy until progression; no MRD-guided stopping.","Cross-trial comparisons with venetoclax regimens are indirect.","Overall survival was not significantly different at early follow-up."],"changedPractice":true,"participants":535},"route":"/key-papers/paper-elevate-tn-acalabrutinib-lancet-2020/","neighbours":{"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":"btk","kind":"target","name":"BTK (Bruton tyrosine kinase)","route":"/targets/btk/"},{"id":"cd20","kind":"target","name":"CD20","route":"/targets/cd20/"}],"drug":[{"id":"acalabrutinib","kind":"drug","name":"Acalabrutinib","route":"/drugs/acalabrutinib/"},{"id":"ibrutinib","kind":"drug","name":"Ibrutinib","route":"/drugs/ibrutinib/"},{"id":"obinutuzumab","kind":"drug","name":"Obinutuzumab","route":"/drugs/obinutuzumab/"},{"id":"zanubrutinib","kind":"drug","name":"Zanubrutinib","route":"/drugs/zanubrutinib/"}],"company":[{"id":"astrazeneca","kind":"company","name":"AstraZeneca","route":"/companies/astrazeneca/"}],"term":[{"id":"pfs","kind":"term","name":"Progression-free survival (PFS)","route":"/terms/pfs/"}],"trial":[{"id":"elevate-tn","kind":"trial","name":"ELEVATE-TN","route":"/trials/elevate-tn/"},{"id":"sequoia","kind":"trial","name":"SEQUOIA","route":"/trials/sequoia/"}],"bottleneck":[{"id":"b-drug-pricing","kind":"bottleneck","name":"Prices and value","route":"/bottlenecks/b-drug-pricing/"},{"id":"b-toxicity-qol","kind":"bottleneck","name":"Toxicity and quality of life are undervalued","route":"/bottlenecks/b-toxicity-qol/"}],"journal":[{"id":"lancet","kind":"journal","name":"The Lancet","route":"/journals/lancet/"}],"person":[{"id":"john-byrd","kind":"person","name":"John C. Byrd","route":"/people/john-byrd/"}]}}