Table 2.
Selected novel bridging to transplant strategies for elderly AML patients.
| Therapy | Reference | Type of Study | N | CR% | alloHCT% | PFS | OS | NRM% | Remarks |
|---|---|---|---|---|---|---|---|---|---|
| Azacitidine | [58] | Prospective, Phase III (Azacitidine vs. conventional care) |
488 (241 Aza vs. 247 CC) |
19.5% (+8.3% CRi) |
- | 6.7 months | 10.4 months | 16.2% | Selected patients not eligible for allo-HSCT |
| [61] | Retrospective (Azacitidine pretreatment before allo-HCT in HR-MDS and sAML) |
20 | 20% | 100% | 145 days | 202 days | n.d. | Incidence of grade II to IV acute GVHD was significantly lower with Azacitidine pretreatment | |
| [60] | Prospective (Azacitidine followed by HSCT vs. no HSCT in MDS and AML) |
97 (19 with AML) |
24% | 56% | n.d. | HSCT: 20.9 months; No HSCT: 9.4 months |
n.d. | Azacitidine responders had a significantly longer survival than non-responders | |
| [62] | Retrospective (Azacitine vs. induction before allo-HCT in MDS and sAML) |
68 | n.d. | 100% | n.d. | estimated 1-year OS 57% | n.d. | Pre-HSCT azacitidine led to a 66% lower hazard of relapse than conventional induction | |
| Decitabine | [57] | Retrospective (Decitabine before allo-HSCT in MDS and AML) |
15 (5 with AML) |
33% | 100% | n.d. | Longtime survival in 6 patients (40%), 2 with AML | 33% (all transplant associated) |
|
| [55] | Prospective (Decitabine vs. conventional care) |
485 | 27.7% (CR + CRi) |
- | n.d. | 7.7 months | 24% | Selected patients not eligible for allo-HSCT | |
| [56] | Prospective, Phase II | 53 | 47% | 8% | 55 weeks | 46 weeks | 15% (60 days) |
CR rate of 50% in complex karyotypes | |
| [54] | Prospective | 116 | 46% | n.d. | n.d. | n.d. | n.d. | CR rate of 67% in cytogenetic unfavorable risk group and 100% with TP53 mutations | |
| Guadecit abine | [63] | Prospective, Phase II (5 or 10 day schedule of Guadecitabine) |
107 | 50-59% | 5% | n.d. | 10.5 / 9.5 months | 22% | Schedule of 60 mg/m2 on day 1–5 recommended |
| CPX-351 | [64] | Prospective, Phase II (CPX-351 vs. 7 + 3) |
126 (85 CPX-351, 41 7 + 3) |
48,8% (+17.9% CRi) |
16.5% | 6.5 months | 14.7 months | 4.7% (60 days) |
In sAML subgroup CPX-351 significantly improved OS (12.1 vs. 6.1 months) |
|
CPX-351
Venetoclax and LDAC |
[65] | Prospective, Phase III (CPX-351 vs. 7 + 3) |
309 (153 CPX-351, 156 7 + 3) |
47.7% (CR + CRi) |
n.d. | n.d. | 9.56 months | 13.7% (60 days) |
|
| [66] | Prospective, Phase Ib/II | 71 | 62% (CR + CRi) |
1% | n.d. | 11.4 months | 1% | ||
| Venetoclax and HMA | [67] | Prospective, Phase Ib (Venetoclax + Decitabine or Azacitidine, dose escalation) |
57 | 61% (CR + CRi) |
18% | n.d. | 12.3 months | 7% | Equal response and safety profile in combination with azacitidine and decitabine |
Selected novel bridging to transplant strategies for elderly AML patients.