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ELEVATE-RR

Acalabrutinib versus ibrutinib in previously treated chronic lymphocytic leukemia: results of the first randomized phase III trial

Phase 3N = 533NCT02477696

Population
Previously treated CLL with centrally confirmed del(17)(p13.1) or del(11)(q22.3)
Design
Open-label, randomised, noninferiority phase 3 trial; patients with previously treated CLL and centrally confirmed del(17)(p13.1) or del(11)(q22.3) randomly assigned to acalabrutinib 100 mg twice daily or ibrutinib 420 mg once daily until progression or unacceptable toxicity. Primary endpoint: independent review committee-assessed noninferiority of PFS.
Primary endpoint
PFS
Arms
  • Acalabrutinib (experimental, n = 268): Acalabrutinib 100 mg twice daily
  • Ibrutinib (control, n = 265): Ibrutinib 420 mg once daily
People
Byrd JC, senior author Jurczak W
PFSHR 1.00 (95% CI 0.79–1.27)Δ median PFS0 monthsOSHR 0.82 (95% CI 0.59–1.15)
Show the numbers
Results reported for ELEVATE-RR
EndpointAnalysisAcalabrutinibIbrutinibEffect
PFSRandomly assigned patients (n=533); the abstract does not state the analysis populationprimarymedian follow-up 40.9 monthsByrd 2021median 38.4 months (33.0–38.6)median 38.4 months (33.0–41.6)HR 1.00 (95% CI 0.79–1.27)Noninferiority analysis (independent review committee); acalabrutinib determined noninferior to ibrutinib.
OSRandomly assigned patients (n=533); the abstract does not state the analysis populationprimarymedian follow-up 40.9 monthsByrd 2021——HR 0.82 (95% CI 0.59–1.15)Secondary endpoint; median OS not reached in either arm; 63 (23.5%) deaths with acalabrutinib and 73 (27.5%) with ibrutinib.
Results reported for ELEVATE-RR
EndpointAnalysisAcalabrutinibIbrutinibEffect
PFSRandomly assigned patients (n=533); the abstract does not state the analysis populationprimarymedian follow-up 40.9 monthsByrd 2021median 38.4 months (33.0–38.6)median 38.4 months (33.0–41.6)HR 1.00 (95% CI 0.79–1.27)Noninferiority analysis (independent review committee); acalabrutinib determined noninferior to ibrutinib.
OSRandomly assigned patients (n=533); the abstract does not state the analysis populationprimarymedian follow-up 40.9 monthsByrd 2021——HR 0.82 (95% CI 0.59–1.15)Secondary endpoint; median OS not reached in either arm; 63 (23.5%) deaths with acalabrutinib and 73 (27.5%) with ibrutinib.
Hazard ratio (95% CI) by endpoint. Values below 1 favour the experimental arm.
PFSOS0.512◀ experimentalcontrol ▶
Data table
EndpointHR95% CI
PFS10.79–1.27
OS0.820.59–1.15
Illustrative — modelled from reported values, not trial data. PFS, primary.
0%25%50%75%100%020406080Months (modelled)
  • Acalabrutinib (experimental)
  • Ibrutinib (control)

Median-only curves assume a constant hazard (exponential) and fit plateaus, as seen with some immunotherapies, poorly.

Data table (modelled values)
MonthsAcalabrutinibIbrutinib
0100.0%100.0%
2464.8%64.8%
4842.0%42.0%
7227.3%27.3%
9617.7%17.7%
Primary publication: Byrd JC, Hillmen P, Ghia P, Kater AP, Chanan-Khan A, Furman RR, et al. Acalabrutinib Versus Ibrutinib in Previously Treated Chronic Lymphocytic Leukemia: Results of the First Randomized Phase III Trial. J Clin Oncol. 2021;39(31):3441-3452. PubMedDOI

Appears in

Sources

  1. Byrd JC, Hillmen P, Ghia P, Kater AP, Chanan-Khan A, Furman RR, et al. Acalabrutinib Versus Ibrutinib in Previously Treated Chronic Lymphocytic Leukemia: Results of the First Randomized Phase III Trial. J Clin Oncol. 2021;39(31):3441-3452.

    PubMedDOI