Table 1.
Studies using HMA for relapse prevention after allo-HSCT in AML.
| Reference | HMA | Study design | Number of patients (disease) | Median age, yrs | Schedule | Median starting time | No of cycles median | GVHD incidence | Response |
|---|---|---|---|---|---|---|---|---|---|
| de Lima et al. ( 66 ) | AZA | Phase I | 45 (AML: 37; MDS: 8) |
60 (24–73) | 8, 16, 24, 32 and 40 mg/m2
d1–5 |
+40 | 1–4 | Acute GVHD Grades II–III: 27% chronic GVHD: 37% |
- 1-yr EFS: 58% - 1-yr OS: 77% |
| Platzbecker et al. ( 67 ) RELAZA trial | AZA | Prospective Preemptive (detection of MRD after transplant) |
20 (AML: 17; MDS: 3) |
58 (20–74) | 75 mg/m2
d1–7 |
+169 | 4 (1–11) | —— | - 16 Patients (80%) responded (increase or stable CD34+ with no relapse) |
| Oshikawa et al. ( 68 ) | AZA | Retrospective matched cohort study | 10 (AML) | 49 (17–65) | 30 mg/m2 d1–7 + GO 3 mg/m2 d 8 |
+78 | 1.5 (1–4) | —— | - 1-yr OS (70% in AZA-GO group vs. 59.8% in controls) - 1-yr DFS (60% vs. 42.8%) |
| Pusic et al. ( 69 ) | DAC | Prospective dose finding | 22 (AML:17; MDS:5) |
59 (21–68) | 5, 7.5, 10 and 15 mg/m2
d1–5 |
+50 to +100 | 5 (1–8) | Acute GVHD grades I–II: 27% grades III–IV: 9% |
- 2-yr OS: 56% - 2-yr DFS: 48% |
| Han et al. ( 70 ) | DAC | Phase I | 16 (AML:5; MDS:11) |
49 | 5 mg/m2
d1–5 then individualized |
+86 | 1–4 | Chronic GVHD: 12.5% | ——– |
|
Craddock et al. (
71
)
RICAZA trial |
AZA | Prospective | 37 (AML) | 60 (40–71) | 36 mg/m2 d1.5 | +54 | 3–10 | Acute GVHD grades I–II: 46% grades III–IV: 0% |
- 1-yr OS: 81% - 2-yr OS: 49% - 1-yr RFS:57% - 2-yr RFS: 49% |
| El Cheikh et al. ( 72 ) | AZA | Observational | 18 (AML:13; MDS:5) |
58 (16–65) | 32 mg/m2 d1–5 | +60 | 16 (1–45) | Acute GVHD ≧̸ grade II: 28% | - 1-yr OS: 70% - 1-yr DFS: 63% |
| Platzbecker et al. ( 73 ) RELAZA 2 | AZA | Prospective Phase II Preemptive (detection of MRD after transplant) |
53 (AML:48; MDS:5) |
59 (52–69) | 75 mg/m2
d1–7 |
—— | Up to 24 | Acute GVHD grade III: 2% |
- 1-yr RFS: 46% |
| Oran et al. ( 74 ) | AZA | RCT | 187 AML/MDS AZA (93) Ct (94) |
57 | 32 mg/m2 d1–5 | +42 to +100 | 4 (1–12) | —— | Median RFS: AZA: 2.07 yrs Ct: 1.28 yrs p = 0.43 |
| de Lima et al. ( 75 ) | CC-486 | Prospective Phase I/II dose finding |
30 (AML: 26; MDS:4) |
64 (28–80) | 150–300 mg d1–7 or d1–14 | +42 to +84 | 9 (1–12) | Acute GVHD grade III: 10% |
- 1-yr OS: 86% (7-day cohort) - 1-year OS: 81% (14-day cohort) |
| Marini et al. ( 76 ) | AZA | Retrospective | 32 Pro: 21 Pre: 11 |
Pro: 58 (15–69) Pre: 52 (30–63) |
Pro: 32 mg/m2 d1–5 Pre: 75 mg/m2 d1–5/7 |
Pro: +116 Pre: +138 |
Pro: 6 (1–18) Pre: 4 (4–22) |
All GVHD:40% | Pro: - 1-yr OS: 100% - 1-yr EFS: 95% Pre: - 1-yr OS: 82% - 1-yr EFS: 54% |
HMA, hypomethylating agent; AZA, 5-azacytidine; EFS, event-free survival; OS, overall survival; GO, gemtuzumab ozogamicin; DFS, disease-free survival; DAC, decitabine; RFS, relapse-free survival; RCT, randomized controlled study; pts, patients; Ct, control arm; yrs, years; pro, prophylaxis; pre, preemptive.