IRIS
Needs reviewImatinib compared with interferon and low-dose cytarabine for newly diagnosed chronic-phase chronic myeloid leukemia
Phase 3N = 1,106NCT00006343NCT00333840
- Population
- Newly diagnosed chronic-phase CML
- Design
- Open-label multicenter randomized trial; crossover allowed if stringent criteria for treatment failure or intolerance were met. The 2017 long-term report gives the initial primary end point as event-free survival (not reported in the 2003 abstract) and, for the long-term analysis, overall survival in the imatinib group.
- Primary endpoint
- EFS
- Arms
- Imatinib (experimental, n = 553): Imatinib 400 mg daily
- IFN-α + cytarabine (control, n = 553): Interferon alfa + low-dose cytarabine
- People
- O'Brien SG, senior author Druker BJ, IRIS Investigators
Δ 18-month MCyR+52.4 pointsΔ 18-month CCyR+61.7 pointsΔ 18-month FFP+5.2 points
Show the numbers
| Endpoint | Analysis | Imatinib | IFN-α + cytarabine | Effect |
|---|---|---|---|---|
| MCyRAll randomly assigned patients (n=1106); the abstract of the primary report does not state the analysis population0–35% Philadelphia-positive metaphases | primarymedian follow-up 19 monthsO'Brien 2003 | 87.1% at 18 mo (84.1–90.0%) | 34.7% at 18 mo (29.3–40.0%) | P<0.001 |
| CCyRAll randomly assigned patients (n=1106); the abstract of the primary report does not state the analysis population | primarymedian follow-up 19 monthsO'Brien 2003 | 76.2% at 18 mo (72.5–79.9%) | 14.5% at 18 mo (10.5–18.5%) | P<0.001 |
| FFPAll randomly assigned patients (n=1106); the abstract of the primary report does not state the analysis populationFreedom from progression to accelerated phase or blast crisis | primaryO'Brien 2003 | 96.7% at 18 mo | 91.5% at 18 mo | P<0.001 |
| OSPatients randomly assigned to imatinib (n=553), intention-to-treat population of the imatinib group | long term-updatemedian follow-up 10.9 yearsHochhaus 2017 | 83.3% at 10 y | — | 65.6% of the control arm crossed over to imatinib (median 0.8 years on control therapy first), so the long-term analysis focuses on the imatinib arm and there is no valid OS comparison between arms. At 10 years 20.1% of the imatinib group had unknown survival status (censored at last contact), so the estimate rests on incomplete follow-up. |
| Endpoint | Analysis | Imatinib | IFN-α + cytarabine | Effect |
|---|---|---|---|---|
| MCyRAll randomly assigned patients (n=1106); the abstract of the primary report does not state the analysis population0–35% Philadelphia-positive metaphases | primarymedian follow-up 19 monthsO'Brien 2003 | 87.1% at 18 mo (84.1–90.0%) | 34.7% at 18 mo (29.3–40.0%) | P<0.001 |
| CCyRAll randomly assigned patients (n=1106); the abstract of the primary report does not state the analysis population | primarymedian follow-up 19 monthsO'Brien 2003 | 76.2% at 18 mo (72.5–79.9%) | 14.5% at 18 mo (10.5–18.5%) | P<0.001 |
| FFPAll randomly assigned patients (n=1106); the abstract of the primary report does not state the analysis populationFreedom from progression to accelerated phase or blast crisis | primaryO'Brien 2003 | 96.7% at 18 mo | 91.5% at 18 mo | P<0.001 |
| OSPatients randomly assigned to imatinib (n=553), intention-to-treat population of the imatinib group | long term-updatemedian follow-up 10.9 yearsHochhaus 2017 | 83.3% at 10 y | — | 65.6% of the control arm crossed over to imatinib (median 0.8 years on control therapy first), so the long-term analysis focuses on the imatinib arm and there is no valid OS comparison between arms. At 10 years 20.1% of the imatinib group had unknown survival status (censored at last contact), so the estimate rests on incomplete follow-up. |
Appears in
Sources
O'Brien SG, Guilhot F, Larson RA, et al. Imatinib compared with interferon and low-dose cytarabine for newly diagnosed chronic-phase chronic myeloid leukemia. N Engl J Med. 2003;348(11):994-1004.
Hochhaus A, Larson RA, Guilhot F, et al. Long-Term Outcomes of Imatinib Treatment for Chronic Myeloid Leukemia. N Engl J Med. 2017;376(10):917-927.