Seminal trials in drugs approved for use in MDS by the United States Food and Drug Administration (FDA).
| MDS drug . | Study design . | N . | Results . | Comments . |
|---|---|---|---|---|
| MDS indicates myelodysplastic syndromes; US, United States; EU, European Union; HR, hazard ratio; CR, complete response; BSC, best supportive care; PR, partial response; OS, overall survival; IWG, International Working Group; AML, acute myeloid leukemia; LDAraC, low-dose cytarabine; IC, intensive chemotherapy. | ||||
| Lenalidomide3 | MDS-003: Phase II | 148 transfusion-dependent, lower-risk, del(5q) | Transfusion independence in 67%; cytogenetic CR in 45%; median response duration >2 years | US Registration study. Treatment-related cytopenias shown to correlate with response; cytogenetic CRs in some patients with complex karyo types. |
| Lenalidomide31 | MDS-002: Phase II | 215 transfusion-dependent, lower-risk, non-del(5q) | Transfusion independence in 26%; median response duration 41 weeks Non-FDA approved indication; treatment-related cytopenias have no correlation with response. | |
| Azacitidine (AZA)1 | CALGB 9221: Phase III | 99 randomized to AZA 92 randomized to BSC All MDS subtypes | CR+PR rate 16% for AZA using IWG criteria; Time to AML progression or death longer for AZA (21 vs 12 months, P = .007) | US Registration Study. No significant OS advantage for AZA likely due to crossover allowed for BSC group and mixed MDS population. |
| Azacitidine (AZA)33 | AZA-001: Phase III | 179 randomized to AZA 179 randomized to conventional care (CC: 105 to BSC; 49 to LDAraC; 25 to IC) Higher-risk MDS | CR+PR rate 29% for AZA vs 21% for CC; median OS 24 months for AZA vs 15 months for CC (HR = .58, P = .0001) | EU Registration Study. 34% of patients had AML; results driven by comparison to BSC arm; responses seen particularly in patients with chromosome 7 abnormalities. |
| Decitabine (DAC)2 | Phase III | 89 randomized to DAC 81 randomized to BSC All MDS subtypes | CR+PR rate 17% for DAC; Time to AML progression or death longer for DAC only in higher-risk group (11 vs 6 months, P = .028) | US Registration Study. Did not meet primary endpoint due to low median # cycles given and mixed MDS population. |
| Decitabine (DAC)36 | EORTC 06011: Phase III | 119 randomized to DAC 114 randomized to BSC Higher-risk MDS | CR+PR rate 23% for DAC; median OS 10.1 months for DAC vs 8.5 months for BSC (HR = .88, P = .38) | No significant OS advantage for DAC likely due to fewer median cycles given (4). |
| MDS drug . | Study design . | N . | Results . | Comments . |
|---|---|---|---|---|
| MDS indicates myelodysplastic syndromes; US, United States; EU, European Union; HR, hazard ratio; CR, complete response; BSC, best supportive care; PR, partial response; OS, overall survival; IWG, International Working Group; AML, acute myeloid leukemia; LDAraC, low-dose cytarabine; IC, intensive chemotherapy. | ||||
| Lenalidomide3 | MDS-003: Phase II | 148 transfusion-dependent, lower-risk, del(5q) | Transfusion independence in 67%; cytogenetic CR in 45%; median response duration >2 years | US Registration study. Treatment-related cytopenias shown to correlate with response; cytogenetic CRs in some patients with complex karyo types. |
| Lenalidomide31 | MDS-002: Phase II | 215 transfusion-dependent, lower-risk, non-del(5q) | Transfusion independence in 26%; median response duration 41 weeks Non-FDA approved indication; treatment-related cytopenias have no correlation with response. | |
| Azacitidine (AZA)1 | CALGB 9221: Phase III | 99 randomized to AZA 92 randomized to BSC All MDS subtypes | CR+PR rate 16% for AZA using IWG criteria; Time to AML progression or death longer for AZA (21 vs 12 months, P = .007) | US Registration Study. No significant OS advantage for AZA likely due to crossover allowed for BSC group and mixed MDS population. |
| Azacitidine (AZA)33 | AZA-001: Phase III | 179 randomized to AZA 179 randomized to conventional care (CC: 105 to BSC; 49 to LDAraC; 25 to IC) Higher-risk MDS | CR+PR rate 29% for AZA vs 21% for CC; median OS 24 months for AZA vs 15 months for CC (HR = .58, P = .0001) | EU Registration Study. 34% of patients had AML; results driven by comparison to BSC arm; responses seen particularly in patients with chromosome 7 abnormalities. |
| Decitabine (DAC)2 | Phase III | 89 randomized to DAC 81 randomized to BSC All MDS subtypes | CR+PR rate 17% for DAC; Time to AML progression or death longer for DAC only in higher-risk group (11 vs 6 months, P = .028) | US Registration Study. Did not meet primary endpoint due to low median # cycles given and mixed MDS population. |
| Decitabine (DAC)36 | EORTC 06011: Phase III | 119 randomized to DAC 114 randomized to BSC Higher-risk MDS | CR+PR rate 23% for DAC; median OS 10.1 months for DAC vs 8.5 months for BSC (HR = .88, P = .38) | No significant OS advantage for DAC likely due to fewer median cycles given (4). |