The recent trials including RIF or ATO plus ATRA as frontline treatment of APL patients
| Reference . | Type of study setting . | Arsenic type . | No. of patients . | % high risk . | Induction . | HCR % . | ED % . | DS % . | Hepatic toxicity % . | Consolidation . | Maintenance . | MCR % . | CIR % . | DFS % . | EFS % . | OS % . |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Lo-Coco 201310 | Randomized phase 3 | ATO | 77 | 0 | ATO 0.15 mg/kg/d + ATRA 45 mg/m2/d | 100 | 0 | 19 | 63 (grade 3-4) | ATRA 45 mg/m2/d 2 wk on/2 wk off for 7 mo ATO 0.15 mg/kg/d 4 wk on/4 wk off for 7 mo | No | 100 | 1 (2 y) | 97 (2 y) | 97 (2 y) | 99 (2 y) |
| Zhu 201321 | Randomized phase 3 | RIF | 111 | 19 | RIF 60 mg/kg/d + ATRA 25 mg/m2/d | 99.1 | 0.9 | 19 | 64.9 | Chemotherapy 3 cycles | ATRA 25 mg/m2/d for 2 wk/mo (in mo 1) + RIF 60 mg/kg/d for 2 wk/mo (in mo 2 and mo 3) for 2 y RIF 60 mg/kg/d for 2 wk/mo (in mo 2 and mo 3) for 2 y | 100 | n = 1 | 98.1 (2 y) | 99.1 (3 y) | |
| ATO | 114 | 21 | ATO 0.16 mg/kg/d + ATRA 25 mg/m2/d | 97.4 | 2.6 | 24.8 | 74.5 | Chemotherapy 3 cycles | ATRA 25 mg/m2/d for 2 wk/mo (in mo1) + ATO 0.16 mg/kg/d for 2 wk/mo (in mo 2 and mo 3) for 2 y | 100 | n = 1 | 95.5 (2 y) | 96.6 (3 y) | |||
| Zhu 201430 | Nonrandomized | RIF | 20 | 0 | RIF 60 mg/kg/d + ATRA 25 mg/m2/d | 100 | 0 | 10 | 55 | ATRA 25 mg/m2/d 2 wk on/2 wk off for 7 mo RIF 60 mg/kg/d 4 wk on/4 wk off for 7 mo | No | 100 | n = 0 | 100 (14 mo and 4 y) | 100 (14 mo and 4 y) | |
| Burnett 201512 | Randomized phase 3 | ATO | 116 | 26 | ATO 0.3 mg/kg/days 1-5 → 0.25 mg/kg, 2/wk, wk 2-8 ATRA 45 mg/m2/d + GO in high-risk | 94 | 4 | 19 | 71 | ATRA 45 mg/m2/d 2 wk on/2 wk off for 7 mo ATO 0.25 mg/kg twice weekly 4 wk on/4 wk off for 7 mo | No | NA | 1 (4 y) | 97 (4 y) | 91 (4 y) | 93 (4 y) |
| Iland 201513 | Nonrandomized | ATO | 124 | 18 | ATO 0.15 mg/kg/days 9-36 + ATRA 45 mg/m2/days 1-36 + IDA 6, 9, or 12 mg/m2/days 2, 4, 6, 8 | 95 | 3 | 14 | 44 | ATRA 45 mg/m2/d + ATO 0.15 mg/kg/d for 28 days for 1st cycle ATRA 45 mg/m2/d days 1-7, 15-21, and 29-35 + ATO 0.15 mg/kg/d 5 d per week for 5 wk for 2nd cycle | ATRA 45 mg/m2/days 1-14 every 90 d 6-MP 50-90 mg/m2/wk days 15-90 MTX 5-15 mg/m2/wk PO days 15-90 × 8 cycles | 100 | 97 (5 y) | 95 (5 y) | 94 (5 y) | |
| Abaza 201715 | Nonrandomized | ATO | 187 | 28.9 | ATO 0.15 mg/kg/d + ATRA 45 mg/m2/d + GO in high-risk | 96 | 4 | 11 | 14 (grade 3-4) | ATRA 45 mg/m2/d 2 wk on/2 wk off for 7 mo ATO 0.15 mg/kg/d 4 wk on/4 wk off for 7 mo | No | 98 | 4 (5 y) | 96 (5 y) | 85 (5 y) | 88 (5 y) |
| Zhu 201838 | Nonrandomized | RIF | 20 | 100 | RIF 60 mg/kg/d + ATRA 25 mg/m2/d + GO in low-dose chemo | 100 | 0 | 35 | 45 | ATRA 25 mg/m2/d 2 wk on/2 wk off for 7 mo RIF 60 mg/kg/d 4 wk on/4 wk off for 7 mo | No | 100 | 10 | 89.4 (3 y) | 100 (3 y) | |
| Zhu 201823 | Randomized phase 3 | RIF | 69 | 0 | RIF 60 mg/kg/d + ATRA 25 mg/m2/d | 100 | 0 | 26 | 58 | ATRA 25 mg/m2/d 2 wk on/2 wk off for 7 mo RIF 60 mg/kg/d 4 wk on/4 wk off for 7 mo | No | 100 | 3 (2 y) | 97 (2 y) | 100 (2 y) | |
| ATO | 36 | 0 | ATO 0.16 mg/kg/d + ATRA 25 mg/m2/d | 94 | 6 | 28 | 78 | ATRA 25 mg/m2/d 2 wk on/2 wk off for 7 mo ATO 0.16 mg/kg/d 4 wk on/4 wk off for 7 mo | No | 100 | 0 (2 y) | 94 (2 y) | 94 (2 y) | |||
| Yang 201847 | Randomized phase 3 (children) | RIF | 40 | 20 | RIF 135 mg/kg/d + ATRA 25 mg/m2/d + mitoxantrone | 100 | 0 | 2.5 | 5 (grade 3-4) | Chemotherapy-based 3 cycles | ATRA+RIF/MTX-6MP/ATRA/MTX-6MP in mo 1-3 for 8 cycles (2 y) | 100 | 0 (5 y) | 100 (5 y) | 100 (5 y) | |
| ATO | 42 | 33.3 | ATO 0.16 mg/kg/d + ATRA 25 mg/m2/d + mitoxantrone | 100 | 0 | 9.5 | 2.4 (grade 3-4) | Chemotherapy-based 3 cycles | ATRA+ATO/MTX-6MP/ATRA/MTX-6MP in mo 1-3 for 8 cycles (2 y) | 100 | 0 (5 y) | 100 (5 y) | 100 (5 y) |
| Reference . | Type of study setting . | Arsenic type . | No. of patients . | % high risk . | Induction . | HCR % . | ED % . | DS % . | Hepatic toxicity % . | Consolidation . | Maintenance . | MCR % . | CIR % . | DFS % . | EFS % . | OS % . |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Lo-Coco 201310 | Randomized phase 3 | ATO | 77 | 0 | ATO 0.15 mg/kg/d + ATRA 45 mg/m2/d | 100 | 0 | 19 | 63 (grade 3-4) | ATRA 45 mg/m2/d 2 wk on/2 wk off for 7 mo ATO 0.15 mg/kg/d 4 wk on/4 wk off for 7 mo | No | 100 | 1 (2 y) | 97 (2 y) | 97 (2 y) | 99 (2 y) |
| Zhu 201321 | Randomized phase 3 | RIF | 111 | 19 | RIF 60 mg/kg/d + ATRA 25 mg/m2/d | 99.1 | 0.9 | 19 | 64.9 | Chemotherapy 3 cycles | ATRA 25 mg/m2/d for 2 wk/mo (in mo 1) + RIF 60 mg/kg/d for 2 wk/mo (in mo 2 and mo 3) for 2 y RIF 60 mg/kg/d for 2 wk/mo (in mo 2 and mo 3) for 2 y | 100 | n = 1 | 98.1 (2 y) | 99.1 (3 y) | |
| ATO | 114 | 21 | ATO 0.16 mg/kg/d + ATRA 25 mg/m2/d | 97.4 | 2.6 | 24.8 | 74.5 | Chemotherapy 3 cycles | ATRA 25 mg/m2/d for 2 wk/mo (in mo1) + ATO 0.16 mg/kg/d for 2 wk/mo (in mo 2 and mo 3) for 2 y | 100 | n = 1 | 95.5 (2 y) | 96.6 (3 y) | |||
| Zhu 201430 | Nonrandomized | RIF | 20 | 0 | RIF 60 mg/kg/d + ATRA 25 mg/m2/d | 100 | 0 | 10 | 55 | ATRA 25 mg/m2/d 2 wk on/2 wk off for 7 mo RIF 60 mg/kg/d 4 wk on/4 wk off for 7 mo | No | 100 | n = 0 | 100 (14 mo and 4 y) | 100 (14 mo and 4 y) | |
| Burnett 201512 | Randomized phase 3 | ATO | 116 | 26 | ATO 0.3 mg/kg/days 1-5 → 0.25 mg/kg, 2/wk, wk 2-8 ATRA 45 mg/m2/d + GO in high-risk | 94 | 4 | 19 | 71 | ATRA 45 mg/m2/d 2 wk on/2 wk off for 7 mo ATO 0.25 mg/kg twice weekly 4 wk on/4 wk off for 7 mo | No | NA | 1 (4 y) | 97 (4 y) | 91 (4 y) | 93 (4 y) |
| Iland 201513 | Nonrandomized | ATO | 124 | 18 | ATO 0.15 mg/kg/days 9-36 + ATRA 45 mg/m2/days 1-36 + IDA 6, 9, or 12 mg/m2/days 2, 4, 6, 8 | 95 | 3 | 14 | 44 | ATRA 45 mg/m2/d + ATO 0.15 mg/kg/d for 28 days for 1st cycle ATRA 45 mg/m2/d days 1-7, 15-21, and 29-35 + ATO 0.15 mg/kg/d 5 d per week for 5 wk for 2nd cycle | ATRA 45 mg/m2/days 1-14 every 90 d 6-MP 50-90 mg/m2/wk days 15-90 MTX 5-15 mg/m2/wk PO days 15-90 × 8 cycles | 100 | 97 (5 y) | 95 (5 y) | 94 (5 y) | |
| Abaza 201715 | Nonrandomized | ATO | 187 | 28.9 | ATO 0.15 mg/kg/d + ATRA 45 mg/m2/d + GO in high-risk | 96 | 4 | 11 | 14 (grade 3-4) | ATRA 45 mg/m2/d 2 wk on/2 wk off for 7 mo ATO 0.15 mg/kg/d 4 wk on/4 wk off for 7 mo | No | 98 | 4 (5 y) | 96 (5 y) | 85 (5 y) | 88 (5 y) |
| Zhu 201838 | Nonrandomized | RIF | 20 | 100 | RIF 60 mg/kg/d + ATRA 25 mg/m2/d + GO in low-dose chemo | 100 | 0 | 35 | 45 | ATRA 25 mg/m2/d 2 wk on/2 wk off for 7 mo RIF 60 mg/kg/d 4 wk on/4 wk off for 7 mo | No | 100 | 10 | 89.4 (3 y) | 100 (3 y) | |
| Zhu 201823 | Randomized phase 3 | RIF | 69 | 0 | RIF 60 mg/kg/d + ATRA 25 mg/m2/d | 100 | 0 | 26 | 58 | ATRA 25 mg/m2/d 2 wk on/2 wk off for 7 mo RIF 60 mg/kg/d 4 wk on/4 wk off for 7 mo | No | 100 | 3 (2 y) | 97 (2 y) | 100 (2 y) | |
| ATO | 36 | 0 | ATO 0.16 mg/kg/d + ATRA 25 mg/m2/d | 94 | 6 | 28 | 78 | ATRA 25 mg/m2/d 2 wk on/2 wk off for 7 mo ATO 0.16 mg/kg/d 4 wk on/4 wk off for 7 mo | No | 100 | 0 (2 y) | 94 (2 y) | 94 (2 y) | |||
| Yang 201847 | Randomized phase 3 (children) | RIF | 40 | 20 | RIF 135 mg/kg/d + ATRA 25 mg/m2/d + mitoxantrone | 100 | 0 | 2.5 | 5 (grade 3-4) | Chemotherapy-based 3 cycles | ATRA+RIF/MTX-6MP/ATRA/MTX-6MP in mo 1-3 for 8 cycles (2 y) | 100 | 0 (5 y) | 100 (5 y) | 100 (5 y) | |
| ATO | 42 | 33.3 | ATO 0.16 mg/kg/d + ATRA 25 mg/m2/d + mitoxantrone | 100 | 0 | 9.5 | 2.4 (grade 3-4) | Chemotherapy-based 3 cycles | ATRA+ATO/MTX-6MP/ATRA/MTX-6MP in mo 1-3 for 8 cycles (2 y) | 100 | 0 (5 y) | 100 (5 y) | 100 (5 y) |
6-MP, 6-mercaptopurine; DS, differentiation syndrome; ED, early death; GO, gemtuzumab ozogamicin; HCR, hematological complete remission; IDA, idarubicin; MCR, molecular remission; MTX, methotrexate; NA, not applicable; PO, by mouth.