RESONATE-2
Ibrutinib as initial therapy for patients with chronic lymphocytic leukemia
Phase 3N = 269NCT01722487
- Population
- Previously untreated CLL or SLL, age 65 or older; the long-term report describes patients without del(17p)
- Design
- International, open-label randomised phase 3 trial of ibrutinib versus chlorambucil in previously untreated older patients. The primary endpoint was PFS assessed by an independent review committee. The 2022 long-term report (up to 8 years of follow-up) describes the population as without del(17p) and also lists the open-label extension study NCT01724346.
- Primary endpoint
- PFS
- Arms
- Ibrutinib (experimental, n = 136): Ibrutinib 420 mg once daily until disease progression or unacceptable toxicity
- Chlorambucil (control, n = 133): Chlorambucil 0.5-0.8 mg/kg for up to 12 cycles
- People
- Burger JA, RESONATE-2 Investigators
PFSHR 0.16OSHR 0.16Δ 24-month OS+13 pointsΔ ORR+51 pointsPFSHR 0.154 (95% CI 0.108–0.220)Δ 84-month PFS+50 points
Show the numbers
| Endpoint | Analysis | Ibrutinib | Chlorambucil | Effect |
|---|---|---|---|---|
| PFSRandomly assigned patients (n=269); the abstract does not state the analysis population | primarymedian follow-up 18.4 monthsBurger 2015 | — | median 18.9 months | HR 0.16P<0.001Median PFS not reached with ibrutinib. No confidence interval for the hazard ratio in the abstract. |
| OSRandomly assigned patients (n=269); the abstract does not state the analysis population | primarymedian follow-up 18.4 monthsBurger 2015 | 98% at 2 y | 85% at 2 y | HR 0.16P=0.001Estimated survival rate at 24 months. |
| ORRRandomly assigned patients (n=269); the abstract does not state the analysis population | primaryBurger 2015 | 86% | 35% | P<0.001 |
| PFSPatients randomly assigned (n=269, up to 8 years of follow-up); the abstract does not state the analysis population | long term-updatemedian follow-up 82.7 monthsBarr 2022 | 59% at 7 y | 9% at 7 y | HR 0.154 (95% CI 0.108–0.220)PFS at 7 years. Follow-up range 0.1-96.6 months. Arm sizes 136 and 133 are from this report. |
| OSPatients randomly assigned to ibrutinib (n=136), up to 8 years of follow-up | long term-updatemedian follow-up 82.7 monthsBarr 2022 | 78% at 7 y | — | Overall survival at 7 years reported for the ibrutinib arm only in the abstract. |
| Endpoint | Analysis | Ibrutinib | Chlorambucil | Effect |
|---|---|---|---|---|
| PFSRandomly assigned patients (n=269); the abstract does not state the analysis population | primarymedian follow-up 18.4 monthsBurger 2015 | — | median 18.9 months | HR 0.16P<0.001Median PFS not reached with ibrutinib. No confidence interval for the hazard ratio in the abstract. |
| OSRandomly assigned patients (n=269); the abstract does not state the analysis population | primarymedian follow-up 18.4 monthsBurger 2015 | 98% at 2 y | 85% at 2 y | HR 0.16P=0.001Estimated survival rate at 24 months. |
| ORRRandomly assigned patients (n=269); the abstract does not state the analysis population | primaryBurger 2015 | 86% | 35% | P<0.001 |
| PFSPatients randomly assigned (n=269, up to 8 years of follow-up); the abstract does not state the analysis population | long term-updatemedian follow-up 82.7 monthsBarr 2022 | 59% at 7 y | 9% at 7 y | HR 0.154 (95% CI 0.108–0.220)PFS at 7 years. Follow-up range 0.1-96.6 months. Arm sizes 136 and 133 are from this report. |
| OSPatients randomly assigned to ibrutinib (n=136), up to 8 years of follow-up | long term-updatemedian follow-up 82.7 monthsBarr 2022 | 78% at 7 y | — | Overall survival at 7 years reported for the ibrutinib arm only in the abstract. |
Data table
| Endpoint | HR | 95% CI |
|---|---|---|
| PFS | 0.154 | 0.108–0.22 |
- Chlorambucil (control)
Median-only curves assume a constant hazard (exponential) and fit plateaus, as seen with some immunotherapies, poorly.
Data table (modelled values)
| Months | Chlorambucil |
|---|---|
| 0 | 100.0% |
| 12 | 64.4% |
| 24 | 41.5% |
| 35 | 27.7% |
| 47 | 17.8% |
Appears in
Sources
Burger JA, Tedeschi A, Barr PM, Robak T, Owen C, Ghia P, et al. Ibrutinib as Initial Therapy for Patients with Chronic Lymphocytic Leukemia. N Engl J Med. 2015;373(25):2425-37.
Barr PM, Owen C, Robak T, Tedeschi A, Bairey O, Burger JA, et al. Up to 8-year follow-up from RESONATE-2: first-line ibrutinib treatment for patients with chronic lymphocytic leukemia. Blood Adv. 2022;6(11):3440-3450.