# ELEVATE-TN: acalabrutinib, alone or with obinutuzumab, against chemo-immunotherapy in untreated CLL

Source: https://onco.cc/key-papers/paper-elevate-tn-acalabrutinib-lancet-2020/  
OnCo record `paper-elevate-tn-acalabrutinib-lancet-2020` (Key paper). Data CC BY-NC 4.0, attribute "Data from OnCo (onco.cc)"; commercial use needs a licence.

## TL;DR

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.

## Fields

- Kind: Key paper
- Last checked: 2026-09-08
- Journal: The Lancet
- Year: 2020
- DOI: 10.1016/S0140-6736(20)30262-2
- Authors: Sharman JP, Egyed M, Jurczak W, et al.
- 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.
- What it means: 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- Caveats: The comparator, chlorambucil-obinutuzumab, was already being superseded when the trial reported.; Continuous therapy until progression; no MRD-guided stopping.; Cross-trial comparisons with venetoclax regimens are indirect.;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.

## Sources

- PubMed search: https://pubmed.ncbi.nlm.nih.gov/?term=ELEVATE-TN%20acalabrutinib%20obinutuzumab%20chlorambucil%20Sharman%20Lancet%202020
- ClinicalTrials.gov NCT02475681: https://clinicaltrials.gov/study/NCT02475681

## Connected records

- cancers: [Chronic lymphocytic leukaemia](https://onco.cc/cancers/cll/), [Chronic lymphocytic leukaemia, first treatment](https://onco.cc/cancers/cll-treatment-naive/)
- targets: [BTK (Bruton tyrosine kinase)](https://onco.cc/targets/btk/), [CD20](https://onco.cc/targets/cd20/)
- drugs: [Acalabrutinib](https://onco.cc/drugs/acalabrutinib/), [Ibrutinib](https://onco.cc/drugs/ibrutinib/), [Obinutuzumab](https://onco.cc/drugs/obinutuzumab/), [Zanubrutinib](https://onco.cc/drugs/zanubrutinib/)
- companies: [AstraZeneca](https://onco.cc/companies/astrazeneca/)
- terms: [Progression-free survival (PFS)](https://onco.cc/terms/pfs/)
- trials: [ELEVATE-TN](https://onco.cc/trials/elevate-tn/), [SEQUOIA](https://onco.cc/trials/sequoia/)
- bottlenecks: [Prices and value](https://onco.cc/bottlenecks/b-drug-pricing/), [Toxicity and quality of life are undervalued](https://onco.cc/bottlenecks/b-toxicity-qol/)
- journals: [The Lancet](https://onco.cc/journals/lancet/)
- people: [John C. Byrd](https://onco.cc/people/john-byrd/)

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