Table 2.
Results from selected trials with hypomethylating agents in newly diagnosed high-risk MDS. AZA: azacitidine; DEC: decitabine; BSC: best standard of care; CR: complete response; LFS: leukemia-free survival; EFS: event-free survival; DoR: duration of response; OS: overall survival; iv: intravenous; sc: subcutaneous.
| Autor (Reference) | Therapy | Phase | N | Outcomes | |
|---|---|---|---|---|---|
| Monotherapy | Silverman et al., 2002 [45] | AZA vs. BSC | III | 191 | ORR: AZA 60% vs. BSC 5% (p > 0.001) CR: AZA 7% vs. BSC 0% (p = 0.01) LFS: AZA 21 months vs. BSC 13 months (p = 0.007) |
| Fenaux et al., 2009 [46] | AZA vs. BSC | III | 358 | ORR: AZA 29% vs. BSC 12% (p = 0.0001) CR: AZA 17% vs. 8% (p = 0.015) OS: AZA 24.5 months vs. BSC 15 months (p = 0.0001) |
|
| Kantarjian et al., 2006 [48] | DEC vs. BSC | III | 170 | ORR: DEC 17% vs. BSC 0% (p = 0.001) CR: DEC 9% vs. BSC 0% LFS: DEC 12.1 months vs. BSC 7.8 months (p = 0.16) OS: DEC 14.0 vs. BSC 14.9 (p = 0.636) |
|
| Kantarjian et al., 2007 [49] | DEC (20 mg/m2 iv × 5 days vs. 20 mg/m2 sc × 5 days vs. 10 mg/m2 iv × 5 days) | II | 95 | ORR: 73% CR: 34% 18 month EFS: 51% 18 month OS: 56% |
|
| Steensma et al., 2009 [50] | DEC | II | 99 | ORR: 32% CR: 17% OS: 19.4 months |
|
| Combination therapies | Sekeres et al., 2021 [53] | AZA +/− pevonedistat | II | 120 | ORR: AZA + pevonedistat 79.3% vs. AZA 56.7% CR: AZA + pevonedistat 51.7% vs. AZA 26.7% DoR: AZA + pevonedistat 34.6 months vs. AZA 13.1 months EFS: AZA + pevonedistat 20.2 months vs. AZA 14.8 months (p = 0.045) OS: AZA + pevonedistat 23.9 months vs. AZA 19.1 months (p = 0.240) |
| Sallmann et al., 2020 [54] | AZA + magrolimab | I | 33 | ORR: 91% CR: 42% DoR: median not reached OS: median not reached |
|
| Sallman et al., 2021 [55] | AZA + eprenetapopt | Ib/II | 40 (TP53 mut) | ORR: 73% CR: 50% DoR: 8.4 months OS: 10.4 months |
|
| Garcia et al., 2020 [56] | AZA + venetoclax | Ib | 78 | ORR: 77% CR: 37% DoR: 12.9 moths OS: 27.5 months |