Randomized trials evaluating the role of continued (maintenance) therapy with lenalidomide, bortezomib, and bortezomib-based regimen in TE patients
| Study group or source . | Age (median), y; no. of patients . | Induction consolidation therapy . | Maintenance dose, duration of TX . | Improvement in quality of response . | TTP or PFS* . | OS* . | Survival after relapse . | Tolerance . |
|---|---|---|---|---|---|---|---|---|
| Attal et al24 | 55; N = 614 | VAD, VD, and other induction therapy, single or double ASCT; Consolidation: lenalidomide 25 mg/d, days 1-21, every 28 d, 2 cycles | Len 10-15 mg/d continuously† | CR: 25%† (P = .49); VGPR: 76%‡ (P = .13) | 42 mo | OS at 5 y: 79% | 12 mo | Discontinuation because of AEs: 21%; SPM: 26 |
| Placebo | CR: 23%† (P = .49); VGPR: 71%‡ (P = .13) | 24 mo; P < 108 | OS at 5 y: 73% | 12 mo | 15%; SPM: 6 | |||
| Sonneveld et al16 | 57; N = 827 | PAD | Bortezomib 1.3 mg/m2, biweekly for 2 y | CR/nCR: 49%; greater than or equal to VGPR: 76% | 35 mo | OS at 5 y 61% | n.a. | Grade 3 and 4 PNP 5% |
| VAD | Thal 50 mg/d for 2 y | CR/nCR: 38%; greater than or equal to VGPR: 61% | 28 mo; P = .02 | 55%; P = .007 | 8% | |||
| McCarthy et al25 | 59; N = 460 | Any, followed by ASCT | Len 10 mg/d with dose adaptations (5-15 mg/d) continuously† | n.a. | TTP, median 46 mo | No. of deaths 23 | n.a. | Discontinuation because of AEs: 12% or other reasons: 13%; SPM: 15 |
| Placebo | 27 mo; P < .0001 | 39; P = .018 | 78% of Eligible patients of the control group had been crossed over to lenalidomide TX | Because of AEs: 2% or other reasons: 6%; SPM: 6 | ||||
| Palumbo et al26 | 57; N = 273 | Rd-MPR or Rd-ASCT | Len 10 mg/d, days 1-21, continuously† | CR: 43%; | 41.9 mo | OS at 3 y 88.0% | Similar survival after relapse | All patient subgroups benefitted from maintenance therapy with the exception of stage 3 patients |
| None | CR: 28.7%, P < .001 | 21.6 mo | OS at 3 y 79.2%; P = .14 | |||||
| Gay et al33 | 56-57; N = 389 | Rd-CycloRd or ASCT × 1-2 | Len 10 mg/d, days 1-21 plus Pred (50) qod, d 11-28 | 37.5 mo 28.5 mo, | OS at 3 y 83% OS at 3 v 88% | PFS2 at 50 mo | ||
| Len 10 mg/d, days 1-21 | P = .3 | P = .21 | ASCT-LenPred: 66%; RCD-LenPred: 47%; ASCT-Len: 57%; RCD-Len: 51% | |||||
| Jackson et al18 | N = 428; Len: 53 | CTD/CTDa RCT/RCTa ASCT | 10 mg days 1-21 continuously† | Greater number of patients with deeper response (combined analysis of TE and TNE patients) | 50 mo | n.a. | n.a. | Longer duration of maintenance TX reduced risk of relapse; benefit seen in cytogenetic high-risk patients, albeit to lesser degree |
| Control: 54 | None | 28 mo; P < .0001 |
| Study group or source . | Age (median), y; no. of patients . | Induction consolidation therapy . | Maintenance dose, duration of TX . | Improvement in quality of response . | TTP or PFS* . | OS* . | Survival after relapse . | Tolerance . |
|---|---|---|---|---|---|---|---|---|
| Attal et al24 | 55; N = 614 | VAD, VD, and other induction therapy, single or double ASCT; Consolidation: lenalidomide 25 mg/d, days 1-21, every 28 d, 2 cycles | Len 10-15 mg/d continuously† | CR: 25%† (P = .49); VGPR: 76%‡ (P = .13) | 42 mo | OS at 5 y: 79% | 12 mo | Discontinuation because of AEs: 21%; SPM: 26 |
| Placebo | CR: 23%† (P = .49); VGPR: 71%‡ (P = .13) | 24 mo; P < 108 | OS at 5 y: 73% | 12 mo | 15%; SPM: 6 | |||
| Sonneveld et al16 | 57; N = 827 | PAD | Bortezomib 1.3 mg/m2, biweekly for 2 y | CR/nCR: 49%; greater than or equal to VGPR: 76% | 35 mo | OS at 5 y 61% | n.a. | Grade 3 and 4 PNP 5% |
| VAD | Thal 50 mg/d for 2 y | CR/nCR: 38%; greater than or equal to VGPR: 61% | 28 mo; P = .02 | 55%; P = .007 | 8% | |||
| McCarthy et al25 | 59; N = 460 | Any, followed by ASCT | Len 10 mg/d with dose adaptations (5-15 mg/d) continuously† | n.a. | TTP, median 46 mo | No. of deaths 23 | n.a. | Discontinuation because of AEs: 12% or other reasons: 13%; SPM: 15 |
| Placebo | 27 mo; P < .0001 | 39; P = .018 | 78% of Eligible patients of the control group had been crossed over to lenalidomide TX | Because of AEs: 2% or other reasons: 6%; SPM: 6 | ||||
| Palumbo et al26 | 57; N = 273 | Rd-MPR or Rd-ASCT | Len 10 mg/d, days 1-21, continuously† | CR: 43%; | 41.9 mo | OS at 3 y 88.0% | Similar survival after relapse | All patient subgroups benefitted from maintenance therapy with the exception of stage 3 patients |
| None | CR: 28.7%, P < .001 | 21.6 mo | OS at 3 y 79.2%; P = .14 | |||||
| Gay et al33 | 56-57; N = 389 | Rd-CycloRd or ASCT × 1-2 | Len 10 mg/d, days 1-21 plus Pred (50) qod, d 11-28 | 37.5 mo 28.5 mo, | OS at 3 y 83% OS at 3 v 88% | PFS2 at 50 mo | ||
| Len 10 mg/d, days 1-21 | P = .3 | P = .21 | ASCT-LenPred: 66%; RCD-LenPred: 47%; ASCT-Len: 57%; RCD-Len: 51% | |||||
| Jackson et al18 | N = 428; Len: 53 | CTD/CTDa RCT/RCTa ASCT | 10 mg days 1-21 continuously† | Greater number of patients with deeper response (combined analysis of TE and TNE patients) | 50 mo | n.a. | n.a. | Longer duration of maintenance TX reduced risk of relapse; benefit seen in cytogenetic high-risk patients, albeit to lesser degree |
| Control: 54 | None | 28 mo; P < .0001 |
AE, adverse event; CALGB, Cancer and Leukemia Group B; CI, confidence interval; CTD, cyclophosphamide-thalidomide-dexamethasone; CTDa, same as CTD, but dose attenuated; HOVON, Stichting Hemato-Oncologie voor Volwassenen Nederland; HR, hazard ratio; GMMG, German-speaking Myeloma-Multicenter Group; Len, lenalidomide; LenPred, lenalidomide-prednisone; n.a., not available; nCR, near complete remission; PAD, bortezomib-doxorubicin-dexamethasone; PNP, polyneuropathy; qod, every other day; RCD, Revlimid-cyclophosphamide-dexamethasone; RCT, Revlimid-cyclophosphamide-thalidomide; RCTa, same as RCT, but dose attenuated; SPM, secondary primary malignancy; TTP, time to progression; TX, treatment; VAD, vincristine-doxorubicin-dexamethasone; VD, Velcade-dexamethasone.
Median unless otherwise stated.
Until progression of disease or intolerance.
Patients on placebo were not allowed to cross over to lenalidomide after PD.