ENDURANCE
Carfilzomib or bortezomib in combination with lenalidomide and dexamethasone for patients with newly diagnosed multiple myeloma without intention for immediate autologous stem-cell transplantation (ENDURANCE): a multicentre, open-label, phase 3, randomised, controlled trial
Phase 3N = 1,087NCT01863550
- Population
- Patients aged 18 years or older with newly diagnosed multiple myeloma, no high-risk disease, ECOG performance status 0-2, ineligible for or not intending immediate autologous stem-cell transplantation; 516 were randomised at the end of induction to maintenance.
- Design
- Multicentre, open-label phase 3 trial (E1A11) with two randomisations. First: induction with bortezomib-lenalidomide-dexamethasone (VRd) or carfilzomib-lenalidomide-dexamethasone (KRd) for 36 weeks (coprimary endpoint progression-free survival). Second, after induction with a proteasome inhibitor-lenalidomide combination: indefinite-duration (continuous) or fixed-duration (2 years) lenalidomide in standard-risk patients not undergoing up-front autologous stem-cell transplantation (primary endpoint overall survival; 80% power to detect a 50% increase in median survival from 5 years to 7.5 years, two-sided alpha 5%, 395 patients randomised and 204 deaths over 9 years of follow-up).
- Primary endpoint
- PFS, OS
- Arms
- VRd induction (control, n = 542): Bortezomib 1.3 mg/m2, lenalidomide 25 mg days 1-14 and dexamethasone 20 mg, 12 cycles of 3 weeks
- KRd induction (experimental, n = 545): Carfilzomib 36 mg/m2, lenalidomide 25 mg days 1-21 and dexamethasone 40 mg, nine 4-week cycles
- Indefinite-duration lenalidomide (control, n = 260): Lenalidomide maintenance until progression or other stopping criteria
- Fixed-duration lenalidomide (2 years) (experimental, n = 256): Lenalidomide maintenance for 2 years
- People
- Kumar SK, ECOG-ACRIN Cancer Research Group
Δ 84-month OS+0.4 pointsΔ 84-month PFS−6.4 pointsPFSHR 1.04 (95% CI 0.83–1.31)Δ median PFS+0.2 months
Show the numbers
| Endpoint | Analysis | KRd induction / Fixed-duration lenalidomide (2 years) | VRd induction / Indefinite-duration lenalidomide | Effect |
|---|---|---|---|---|
| OSIntention-to-treat population randomised to maintenance at the end of induction (260 indefinite, 256 fixed duration) | primarymedian follow-up 86 monthsKumar 2026 | 69% at 7 y | 68.6% at 7 y | P=0.9380 deaths in each group. Difference -0.4 percentage points (95% CI -9.0 to 8.3), indefinite versus fixed duration. The abstract prints the interval as '95 confidence interval'. |
| PFSIntention-to-treat population randomised to maintenance at the end of induction (260 indefinite, 256 fixed duration) | primarymedian follow-up 86 monthsKumar 2026 | 29.7% at 7 y | 36.1% at 7 y | Difference 6.4 percentage points (95% CI -2.6 to 15.4). 5-year cumulative incidence of second primary cancers excluding nonmelanoma skin cancer 11.2% with indefinite versus 8.3% with fixed-duration lenalidomide; grade 3 or higher nonhematologic events 48.2% versus 31.5%. |
| PFSInduction randomisation, intention to treat (VRd 542, KRd 545), second planned interim analysis | interimKumar 2020 | median 34.6 months (28.8–37.8) | median 34.4 months | HR 1.04 (95% CI 0.83–1.31)P=0.74Induction randomisation (KRd versus VRd). The VRd median has a 95% CI of 30.1 to not estimable, so no interval is stored for that arm. The abstract's reported median follow-up for this analysis is not recorded. |
| Endpoint | Analysis | KRd induction / Fixed-duration lenalidomide (2 years) | VRd induction / Indefinite-duration lenalidomide | Effect |
|---|---|---|---|---|
| OSIntention-to-treat population randomised to maintenance at the end of induction (260 indefinite, 256 fixed duration) | primarymedian follow-up 86 monthsKumar 2026 | 69% at 7 y | 68.6% at 7 y | P=0.9380 deaths in each group. Difference -0.4 percentage points (95% CI -9.0 to 8.3), indefinite versus fixed duration. The abstract prints the interval as '95 confidence interval'. |
| PFSIntention-to-treat population randomised to maintenance at the end of induction (260 indefinite, 256 fixed duration) | primarymedian follow-up 86 monthsKumar 2026 | 29.7% at 7 y | 36.1% at 7 y | Difference 6.4 percentage points (95% CI -2.6 to 15.4). 5-year cumulative incidence of second primary cancers excluding nonmelanoma skin cancer 11.2% with indefinite versus 8.3% with fixed-duration lenalidomide; grade 3 or higher nonhematologic events 48.2% versus 31.5%. |
| PFSInduction randomisation, intention to treat (VRd 542, KRd 545), second planned interim analysis | interimKumar 2020 | median 34.6 months (28.8–37.8) | median 34.4 months | HR 1.04 (95% CI 0.83–1.31)P=0.74Induction randomisation (KRd versus VRd). The VRd median has a 95% CI of 30.1 to not estimable, so no interval is stored for that arm. The abstract's reported median follow-up for this analysis is not recorded. |
Data table
| Endpoint | HR | 95% CI |
|---|---|---|
| PFS | 1.04 | 0.83–1.31 |
- VRd induction (control)
- KRd induction (experimental)
Median-only curves assume a constant hazard (exponential) and fit plateaus, as seen with some immunotherapies, poorly.
Data table (modelled values)
| Months | VRd induction | KRd induction |
|---|---|---|
| 0 | 100.0% | 100.0% |
| 22 | 64.2% | 64.4% |
| 43 | 42.0% | 42.3% |
| 65 | 27.0% | 27.2% |
| 87 | 17.3% | 17.5% |
Appears in
Sources
Kumar SK, Jacobus SJ, Cohen AD, Weiss M, Callander N, Singh AK, et al. Carfilzomib or bortezomib in combination with lenalidomide and dexamethasone for patients with newly diagnosed multiple myeloma without intention for immediate autologous stem-cell transplantation (ENDURANCE): a multicentre, open-label, phase 3, randomised, controlled trial. Lancet Oncol. 2020;21(10):1317-1330.
Kumar S, Jacobus S, Cohen A, Weiss M, Callander N, Singh A, et al. Continuous or Fixed-Duration Maintenance Therapy in Multiple Myeloma. N Engl J Med. 2026;395(3):221-232.