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Bending the Curve Trial by Trial
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E1912

Ibrutinib-rituximab or chemoimmunotherapy for chronic lymphocytic leukemia

Phase 3N = 529NCT02048813

Population
Previously untreated CLL, age 70 years or younger
Design
Phase 3 trial; patients aged 70 or younger with previously untreated CLL randomly assigned 2:1 to ibrutinib-rituximab (six cycles of rituximab after one cycle of ibrutinib alone, then ibrutinib until progression) or six cycles of FCR. Primary endpoint PFS; overall survival secondary. Report of a planned interim analysis.
Primary endpoint
PFS
Arms
  • Ibrutinib-rituximab (experimental, n = 354): Ibrutinib plus rituximab for six cycles (after one cycle of ibrutinib alone), then ibrutinib until disease progression
  • FCR (control, n = 175): Six cycles of fludarabine, cyclophosphamide and rituximab
People
Shanafelt TD, senior author Tallman M
PFSHR 0.35 (95% CI 0.22–0.56)Δ 36-month PFS+16.5 pointsOSHR 0.17 (95% CI 0.05–0.54)Δ 36-month OS+7.3 pointsPFSHR 0.26 (95% CI 0.14–0.50)Δ 36-month PFS+28.2 points
Show the numbers
Results reported for E1912
EndpointAnalysisIbrutinib-rituximabFCREffect
PFSRandomly assigned patients (n=529); planned interim analysis; the abstract does not state the analysis populationinterimmedian follow-up 33.6 monthsShanafelt 201989.4% at 3 y72.9% at 3 yHR 0.35 (95% CI 0.22–0.56)P<0.001PFS at 3 years; results met the protocol-defined efficacy threshold for the interim analysis.
OSRandomly assigned patients (n=529); planned interim analysis; the abstract does not state the analysis populationinterimmedian follow-up 33.6 monthsShanafelt 201998.8% at 3 y91.5% at 3 yHR 0.17 (95% CI 0.05–0.54)P<0.001Overall survival at 3 years.
PFSPatients without IGHV mutation (subgroup)interimShanafelt 201990.7% at 3 y62.5% at 3 yHR 0.26 (95% CI 0.14–0.50)Subgroup analysis; PFS at 3 years.
PFSPatients with IGHV mutation (subgroup)interimShanafelt 201987.7% at 3 y88% at 3 yHR 0.44 (95% CI 0.14–1.36)Subgroup analysis; PFS at 3 years.
Results reported for E1912
EndpointAnalysisIbrutinib-rituximabFCREffect
PFSRandomly assigned patients (n=529); planned interim analysis; the abstract does not state the analysis populationinterimmedian follow-up 33.6 monthsShanafelt 201989.4% at 3 y72.9% at 3 yHR 0.35 (95% CI 0.22–0.56)P<0.001PFS at 3 years; results met the protocol-defined efficacy threshold for the interim analysis.
OSRandomly assigned patients (n=529); planned interim analysis; the abstract does not state the analysis populationinterimmedian follow-up 33.6 monthsShanafelt 201998.8% at 3 y91.5% at 3 yHR 0.17 (95% CI 0.05–0.54)P<0.001Overall survival at 3 years.
PFSPatients without IGHV mutation (subgroup)interimShanafelt 201990.7% at 3 y62.5% at 3 yHR 0.26 (95% CI 0.14–0.50)Subgroup analysis; PFS at 3 years.
PFSPatients with IGHV mutation (subgroup)interimShanafelt 201987.7% at 3 y88% at 3 yHR 0.44 (95% CI 0.14–1.36)Subgroup analysis; PFS at 3 years.
Hazard ratio (95% CI) by endpoint. Values below 1 favour the experimental arm.
PFSOSPFSPFS0.512◀ experimentalcontrol ▶
Data table
EndpointHR95% CI
PFS0.350.22–0.56
OS0.170.05–0.54
PFS0.260.14–0.5
PFS0.440.14–1.36
Primary publication: Shanafelt TD, Wang XV, Kay NE, Hanson CA, O'Brien S, Barrientos J, et al. Ibrutinib-Rituximab or Chemoimmunotherapy for Chronic Lymphocytic Leukemia. N Engl J Med. 2019;381(5):432-443. PubMedDOI

Appears in

Sources

  1. Shanafelt TD, Wang XV, Kay NE, Hanson CA, O'Brien S, Barrientos J, et al. Ibrutinib-Rituximab or Chemoimmunotherapy for Chronic Lymphocytic Leukemia. N Engl J Med. 2019;381(5):432-443.

    PubMedDOI