Table 1.
Thalidomide maintenance studies after ASCT and conventional therapy
| Study group | Median age, y (no. of patients) | Induction therapy | Maintenance dose, duration of treatment | Improvement in quality of response | EFS or PFS* | OS* | Survival after relapse | Thalidomide tolerance |
|---|---|---|---|---|---|---|---|---|
| IFM 99-02: Attal et al15 (2006) | Mean 59 ± 8 (N = 597) | VAD: 3 or 4 cycles, Single ASCT | (A) Thalidomide 400 mg/d until PD | VGPR: (A) 67% | 3-y EFS: (A) 52% | 4-y OS: (A) 87% | 1-y OS: (A) 75% | 39% stopped thalidomide because of side effects, mostly PNP, all grades of PNP 68%, grades 3 or 4: 7% |
| Pamidronate 90 mg, every 4 wks, until PD | ||||||||
| (B) Pamidronate 90 mg, every 4 wks, until PD | (B) 55% | (B) 37% | (B) 74% | (B) 73% | ||||
| (C) None | (C) 57% | (C) 36% | (C) 77% | (C) 78% | ||||
| P = .03 | P < .009 | P < .04 | P = .7 | |||||
| ALLG MM6: Spencer et al16 (2009) | ≤ 70 (N = 243) | Mostly VAD Single ASCT | (A) Thalidomide 100-200 mg/d, for 12 mo | VGPR: (A) 65% | 3-y PFS estimate: (A) 42% | 3-y OS estimate: (A) 86% | 1-y OS estimate: (A) 79% | 30% stopped therapy because of intolerance (mostly PNP), 10% grades 3 or 4 PNP and 9% stopped because of PD |
| Prednisolone 50 mg on alternate days until PD | ||||||||
| (B) Prednisolone 50 mg on alternate days until PD | (B) 44% | (B) 23% | (B) 75% | (B) 77% | ||||
| P = .001 | P < .001 | P = .004 | P = .237 | |||||
| MRC Myeloma IX: Morgan et al17 (2012) | Intensive, 59 (N = 493) | CVAD vs CTD, single ASCT | (A) Thalidomide, 50-100 mg/day, until PD† | No difference in the percentage of patients that upgraded response status P = .19 | PFS: (A) 30 mo | 3-year OS: (A) 75% | (A) 20 mo | 52.2% discontinued maintenance before PD mainly because of adverse events, median duration of treatment: 7 mo‡ |
| (B) None† | (B) 27 mo P = .003 | (B) 80% P = .26 | (B) 36 mo P = .003 | |||||
| Nonintensive, 73 (N = 327) | CTD attenuated vs MP | (A) Thalidomide, 50-100 mg/day, until PD† | PFS: (A) 11 mo | (A) 38 mo | (A) 21 mo | |||
| (B) None† | (B) 9 mo P = .014 | (B) 39 mo P = .995 | (B) 26 mo P = .25 | |||||
| TT2: Barlogie et al18 (2006) | ≤ 75, median NA (N = 668) Median follow-up: 42 mo | (A) 4 induction cycles, double ASCT 4 consolidation cycles, thalidomide 400 mg/d during induction, 100 mg between ASCT, 200 mg with consolidation | (A) Thalidomide 100 mg during the first year, thereafter 50 mg on alternate days, until PD | CR: (A) 62% | 4-y EFS: A) 65% | OS: A) Not stated | Median OS: A) 1.1 y | 30% stopped thalidomide within 2 y |
| (B) Same induction without thalidomide | (B) None | (B) 43% P = .001 | (B) 44% P = .01 | (B) Not stated P = .9 | (B) 2.7 y P = .001 | |||
| TT2: Barlogie et al19 (2008) | Median follow-up: 70 mo | CR: (A) 64%† | EFS median: (A) 6.0 y | 8-y OS estimate: (A) 57% | 5-y OS estimate: (A) 27% | ∼ 80% stopped thalidomide because of toxicity within 2 y† | ||
| (B) 43% | (B) 4.1 y | (B) 44% | (B) 23% | |||||
| P = .001 | P = .001 | P = .09 | P = .11 | |||||
| TT2: Barlogie et al20 (2010) | Median follow-up: 87 mo (N = 668) | NA | EFS median: 4.8 y | OS median 9 y | 7.2 y OS estimate: | NA | ||
| (A) 45.2% | ||||||||
| (B) 42.2% | ||||||||
| P = .27 | ||||||||
| HOVON 50: Lokhorst et al21 (2008) | 56 (N = 556) | VAD vs TAD Single or double ASCT | (A) Thalidomide, 50 mg/d, until PD | VGPR: | EFS: | Median: | Median OS: | PNP grades 2-4: ∼ 50% Treatment discontinued or dose reduced: 58% |
| (A) 66% | (A) 34 mo | (A) 73 mo | (A) 20 mo | |||||
| (B) 22 mo, P < .001 | ||||||||
| (B) IFN-α, 3 MU, 3 times weekly, until PD | (B) 54% | PFS: | (B) 60 mo | (B) 31 mo | ||||
| P = .005 | (A) 34 mo | P = .77 | P = .009 | |||||
| (B) 25 mo P < .001 | ||||||||
| NCIC CTG MY10: Stewart et al22 (2010) | 58 (N = 332) | Induction therapy not specified Single ASCT | (A) Thalidomide 200 mg/d and alternate-day prednisone 50 mg, until PD | PFS: (A) 28 mo | 4-y OS estimate: (A) 68% | Increased toxicity, including PNP and reduced quality of life, improved appetite, and sleep VTE: 7% | ||
| (B) None | (B) 17 mo | (B) 60% | VTE: 0% | |||||
| P < .0001 | P = .21 | |||||||
| CEMSG: Ludwig et al25 (2010) | 72 (N = 124) | Thalidomide/dexamethasone vs MP | (A) Thalidomide 200 mg up to maximum tolerated dose, until PD IFN-α-2b, 3 MU, 3 times weekly | (A) PR to VGPR or CR: 8% | PFS: (A) 27.7 mo | (A) 52.6 mo | OS after PD: (A) 8.1 mo | PNP grades 3 or 4: 11% |
| (B) IFN-α-2b, 3 MU, 3 times weekly | (B) PR to VGPR or CR: 2% | (B) 13.2 mo P = .0068 | (B) 51.4 mo P = .81 | (B) 25.5 mo P = .056 |
*
Data are median values unless otherwise stated.
†
Same regimen for intensive and nonintensive patients.
‡
Results for intensive and nonintensive group combined.