Lenalidomide plus high-dose dexamethasone versus lenalidomide plus low-dose dexamethasone as initial therapy for newly diagnosed multiple myeloma: an open-label randomised controlled trial
N = 445NCT00098475
- Population
- Patients with untreated symptomatic multiple myeloma; trial coordinated by the Eastern Cooperative Oncology Group.
- Design
- Open-label randomised non-inferiority trial in patients with untreated symptomatic myeloma, assigned to lenalidomide 25 mg on days 1-21 of a 28-day cycle with dexamethasone 40 mg on days 1-4, 9-12 and 17-20 (high dose) or on days 1, 8, 15 and 22 (low dose). After four cycles patients could stop to pursue stem-cell transplantation or continue until progression. The primary endpoint was response rate after four cycles by European Group for Blood and Bone Marrow Transplant criteria; the non-inferiority margin was an absolute difference of 15% in response rate. Analysis was by modified intention to treat. The trial was stopped after the second interim analysis and patients on high-dose therapy crossed over to low-dose therapy.
- Primary endpoint
- ORR
- Arms
- Lenalidomide plus high-dose dexamethasone (control, n = 223): Lenalidomide 25 mg days 1-21 of 28 plus dexamethasone 40 mg on days 1-4, 9-12, 17-20
- Lenalidomide plus low-dose dexamethasone (experimental, n = 222): Lenalidomide 25 mg days 1-21 of 28 plus dexamethasone 40 mg on days 1, 8, 15, 22
- People
- Rajkumar SV, Eastern Cooperative Oncology Group
Δ ORR−11 pointsΔ 12-month OS+9 points
Show the numbers
| Endpoint | Analysis | Lenalidomide plus low-dose dexamethasone | Lenalidomide plus high-dose dexamethasone | Effect |
|---|---|---|---|---|
| ORRModified intention to treat (214 and 205 patients evaluable)Complete or partial response within four cycles, by European Group for Blood and Bone Marrow Transplant criteria. | primaryRajkumar 2010 | 68% | 79% | P=0.008169 of 214 versus 142 of 205; odds ratio 1.75 (80% CI 1.30 to 2.32), not a 95% interval. |
| OSRandomised patients (second interim analysis at 1 year) | interimRajkumar 2010 | 96% at 12 mo (94–99%) | 87% at 12 mo (82–92%) | P=0.0002Observed at the second interim analysis, after which the trial was stopped. Grade 3 or worse toxic effects in the first 4 months: 52% (117 patients) with high dose versus 35% (76 of 220) with low dose (p=0.0001); deaths in the first 4 months 12 of 222 versus 1 of 220 (p=0.003). |
| Endpoint | Analysis | Lenalidomide plus low-dose dexamethasone | Lenalidomide plus high-dose dexamethasone | Effect |
|---|---|---|---|---|
| ORRModified intention to treat (214 and 205 patients evaluable)Complete or partial response within four cycles, by European Group for Blood and Bone Marrow Transplant criteria. | primaryRajkumar 2010 | 68% | 79% | P=0.008169 of 214 versus 142 of 205; odds ratio 1.75 (80% CI 1.30 to 2.32), not a 95% interval. |
| OSRandomised patients (second interim analysis at 1 year) | interimRajkumar 2010 | 96% at 12 mo (94–99%) | 87% at 12 mo (82–92%) | P=0.0002Observed at the second interim analysis, after which the trial was stopped. Grade 3 or worse toxic effects in the first 4 months: 52% (117 patients) with high dose versus 35% (76 of 220) with low dose (p=0.0001); deaths in the first 4 months 12 of 222 versus 1 of 220 (p=0.003). |
Appears in
Sources
Rajkumar SV, Jacobus S, Callander NS, Fonseca R, Vesole DH, Williams ME, et al. Lenalidomide plus high-dose dexamethasone versus lenalidomide plus low-dose dexamethasone as initial therapy for newly diagnosed multiple myeloma: an open-label randomised controlled trial. Lancet Oncol. 2010;11(1):29-37.