Table 1.
Summary of placebo controlled, randomized studies of maintenance therapy in AML.
| Trial | Reference Number | Number of patients entering maintenance randomization | Age (Range) | Maintenance treatment regimen | Follow up | Disease/Relapse/Leukemia Free Survival (DFS/RFS/LFS) | Overall Survival (OS) |
|---|---|---|---|---|---|---|---|
| HMA | |||||||
| UK NCRI AML16 | (46) | 530 | 53–84 | Azacitidine vs placebo | 50.4 months | Not reported | No significant difference in OS |
| HOVON97 | (47) | 116 | 60–81 | Azacitidine vs placebo | 41.4 months | Median DFS 15.9 months in azacitidine arm vs 10.3 months in placebo arm | No significant difference in OS |
| QUAZAR AML-001 | (21) | 472 | 55–86 | CC-486 (oral azacitidine) vs placebo | 41.2 months | Median RFS 10.2 months in CC-486 arm vs 4.8 months in placebo arm (p = 0.0001) | Median OS 24.7 months in CC-486 arm vs 14.8 months in placebo arm (p = 0.0009) |
| ECOG-ACRIN E2906 | (48) | 120 | 60–85 | Decitabine vs placebo | 49.8 months | No significant difference in DFS | No significant difference in OS |
| Cytotoxic Chemotherapy | |||||||
| Swiss Group for Clinical Cancer Research | (26) | 74 | 7–65 | Ara-C-thioguanine alternating with Ara-C-predinsone-vincristine vs placebo | 44 months | No significant difference in DFS | No significant difference in OS |
| German AML Cooperative Group | (30) | 145 | 15–78 | Ara-C-daunorubicin alternating with Ara-C–thioguanine and Ara-C-cyclophosphamide vs placebo | 2.5 years | Median RFS 13 months in maintenance arm vs 8 months in the nonmaintenance arm (p = 0.003) | Not Reported |
| SW Leukemia Group | (31) | 32 | 18–74 | Thioguanine and etoposide alternating with CCNU vs placebo | Not Reported | No significant difference in DFS | Not Reported |
| EORTC HOVON | (28) | 147 | 60–88 | Low dose Ara-C vs placebo | 6 years | Median DFS 51 weeks in Ara-C arm vs 29 weeks in no-Ara-C arm (p = 0.006) | No significant difference in OS |
| Finnish Leukemia Group | (27) | 108 | 16–59 | Ara-C-thioguanine vs human leukocyte IFN vs placebo | 82 months | No significant difference in DFS between any of the three arms | No significant difference in OS between any of the three arms |
| Group LAME | (32) | 70 | <20 (range not reported) | Oral mercaptopurine and monthly pulses of subcutaneous cytarabine vs placebo | Not Reported | No significant difference in DFS | OS inferior in maintenance arm (p=0.04) |
| Immunotherapy | |||||||
| Manchester Royal Infirmary | (51) | 41 | Adult patients (median or range not reported) | BCG and irradiated allogeneic myeloblasts vs placebo | Not Reported | Median RFS 35.14 weeks in maintenance arm vs 19.71 weeks in no maintenance arm (p = 0.039) | Median OS 96.14 weeks in maintenance arm vs 53 weeks in no maintenance arm 9p = 0.045) |
| Finnish Leukemia Group | (27) | 108 | 16–59 | Ara-C-thioguanine vs human leukocyte IFN vs placebo | 82 months | No difference in DFS between any of the three arms | No significant difference in OS between any of the three arms |
| UK MRC AML11 | (69) | 362 | 44–75 | IFN-α vs placebo | Not Reported | No significant difference in DFS | No significant difference in OS |
| CALGB 9720 | (57) | 163 | 60–83 | IL-2 vs placebo | Not Reported | No significant difference in DFS | No significant difference in OS |
| AML-12 | (60) | 550 | 15–60 | IL-2 vs placebo | 3.6 years | No significant difference in DFS | No significant difference in OS |
| ALFA-9801 | (59) | 161 | 50–70 | IL-2 vs placebo | 49 months | No significant difference in DFS | No significant difference in OS |
| ELAM02 | (61) | 154 | <18 (range not reported) | IL-2 vs placebo | 49 months | No significant difference in DFS | No significant difference in OS |
| Brune et al. | (68) | 160 | 18–84 | Histamine dihydrochloride plus IL-2 vs placebo | 47 months | 36 month LFS of 34% in HDC/IL-2 arm vs 24% in placebo arm (p = 0.01) | No significant difference in OS |