Table 4 Autophagy-modulating agents used in AML clinical trials
Drug | Target mechanism | enrolled patients | Combination therapy | Phase (status) | Clinical outcomes (N) | Ref |
|---|---|---|---|---|---|---|
Sirolimus | mTOR inhibitor (autophagy induction) | High-risk AML | Mitoxantrone, etoposide, and cytarabine (MEC) | Phase I&II (complete) | ORR: 47% ORR with baseline target inhibition: 71% ORR without target inhibition: 20% | NCT00780104 NCT01184898 [232] |
RAD001 (everolimus) | mTOR inhibitor (autophagy induction) | First relapse AML (under 65 years) | 7 + 3 (cytarabine + daunorubicin) | Phase Ib (complete) | CR: 68% (19/28) FLT3-ITD mutated patient achieved CR (3/4) | NCT01074086[233] |
| Â | Â | Elderly AML | Low-dose Ara-C | Phase Ib (complete) | ORR: 25% (6/24) PR: 4.2% (1/24) | NCT00636922 [234] |
Vitamin D | Autophagy induction | Elderly AML after treatment failure | Deferasirox | Retrospective case–control study | Median survival: 10.4 months vs 4 months (treated vs best supportive care) | [239] |
Bortezomib | Autophagy induction | Elderly, eligible AML/relapsed AML | Weekly idarubicin | Phase I (complete) | CR: 20% (4/20) PR: 5% (1/20) | NCT00382954[240] |
|  |  | Eligible AML | 7 + 3 (cytarabine + daunorubicin) | Phase I&II (complete) | CR: 65% CRp: 4% | [241] |
Chidamide | Autophagy inhibition | Relapse/refractory AML | Decitabine, cytarabine, aclarubicin, and granulocyte colony-stimulating factor | Phase I/II (complete) | CR: 25.8% (24/93) CRi: 20.4% (19/93) PR: 8.6% (8/93) | NCT02886559[243] |