Table 8.
Selected conventional care regimens for patients with AML
| Selected conventional care regimens | |
|---|---|
| Patients eligible for intensive chemotherapy | |
| Induction therapy (all ages) (“7+3”)*,†,‡ | • 3 d of an IV anthracycline: daunorubicin at least 60 mg/m2; idarubicin 12 mg/m2; or mitoxantrone 12 mg/m2, and 7 d of continuous infusion cytarabine (100-200 mg/m2) |
| Consolidation therapy‡,§ | |
| Younger patients (18-60/65 y) | |
| • Favorable-risk genetics | • 2-4 cycles of IDAC (1000-1500 mg/m2 IV over 3 h q12h, d1-3; or 1000-1500 mg/m2 IV over 3 h d1-5 or 6) |
| • Intermediate-risk genetics | • Allogeneic HCT from matched-related or unrelated donor |
| • 2-4 cycles of IDAC (1000-1500 mg/m2 IV over 3 h q12h, d1-3; or 1000-1500 mg/m2 IV over 3 h d1-5 or 6), or | |
| • High-dose therapy and autologous HCT | |
| • Adverse-risk genetics | • Allogeneic HCT from matched-related or unrelated donor |
| Older patients (>60/65 y) | |
| • Favorable-risk genetics | • 2-3 cycles of IDAC (500-1000 mg/m2 IV over 3 h q12h, d1-3; or 500-1000 mg/m2 IV over 3 h d1-5 or 6) |
| • Intermediate/adverse-risk genetics | • No established value of intensive consolidation therapy; consider allogeneic HCT in patients with low HCT-Comorbidity Index, or investigational therapy |
| Patients considered not candidates for intensive chemotherapy|| | |
| Azacitidine¶ | 75 mg/m2, SC, d1-7, q4 wk, until progression |
| Decitabine# | 20 mg/m2, IV, d1-5, q4 wk, until progression |
| Low-dose cytarabine** | Low-dose cytarabine (20 mg q12h, SC, d1-10, q4 wk; until progression); not recommended in patients with adverse-risk genetics |
| Best supportive care | Including hydroxyurea; for patients who cannot tolerate any antileukemic therapy, or who do not wish any therapy |
| Common salvage regimens in patients not responding to a first induction cycle or with relapsed disease who are candidates for intensive therapy | |
| IDAC†† (with or without anthracycline) | IDAC (1000-1500 mg/m2 IV over 3 h q12 h, d1-3 [500-1000 mg/m2 in patients >60 y]; or 1000-1500 mg/m2 IV over 3 h d1-5 or 6 [500-1000 mg/m2 in patients >60 y]); with or without daunorubicin 45-60 mg/m2, IV, d1-3; idarubicin 8-10 mg/m2, IV, d3-5, or mitoxantrone 8-10 mg/m2, IV, d1-3 |
| FLAG-IDA‡‡ | Fludarabine 30 mg/m2 IV, d2-6; cytarabine 1500-2000 mg/m2 IV over 3 h, starting 4 h after fludarabine infusion, d2-6; idarubicin 10 mg/m2 IV, d2-4; G-CSF 5 µg/kg, SC, d1-5; additional G-CSF may be administered starting 7 d after end of chemotherapy until WBC count >500/uL |
| Consider dose reduction in patients >60 y: fludarabine 20 mg/m2; cytarabine 500-1000 mg/m2; idarubicin 8 mg/m2 | |
| MEC | Mitoxantrone 8 mg/m2, d1-5; etoposide 100 mg/m2, d1-5; cytarabine 1000 mg/m2, d1-5 |
| Allogeneic HCT | Consider transplantation for patients with primary refractory disease, for patients in second CR or with major cytoreduction but still active disease following salvage therapy |
| Consider second transplantation under certain conditions (see “Salvage treatment”) | |
| Perform early HLA typing | |
Patients should go on clinical trials if possible.
EMA, European Medicines Agency; FLAG-AMSA, FLAG + amsacrine; FLAG-MITO, FLAG + mitoxantrone; q, every; SC, subcutaneously.
Regimens containing higher doses of cytarabine are generally considered as the best option for patients not responding to a first cycle of “7+3” (see common salvage regimens).
Older patients (in general >65 y) and patients with adverse genetics are less likely to respond to conventional induction therapy and may receive hypomethylating agents, or, preferably, investigational therapy.
Patients, at least those aged 18 to 60 y, with newly diagnosed AML and activating FLT3 mutations may be considered to receive additional therapy with midostaurin (administered after the chemotherapy).61
Results from assessment of MRD should be taken into account for selecting the appropriate consolidation therapy.
For discussion of patients not considered candidates for intensive chemotherapy see first 2 paragraphs of “Current therapy.”
Approved by FDA and EMA for adult patients who are not eligible for HCT with AML with 20% to 30% blasts and multilineage dysplasia; in addition, approved by EMA for patients who are not eligible for allogeneic HCT with AML with >30% marrow blasts.
Approved by EMA (not by FDA) for patients with newly diagnosed de novo or secondary AML, who are not candidates for standard induction chemotherapy.
In some countries used in a dosage of 20 mg/m2 SC once daily.
Evidence from pharmacologic studies and clinical trials in first-line treatment indicate that doses higher than 1500 mg/m2 are above the plateau of the maximal therapeutic effect;147 single-agent IDAC should not be used in patients relapsing within 6 mo following consolidation with higher doses of cytarabine.
Idarubicin may be replaced by mitoxantrone 10 mg/m2, IV, days 2 to 4 (FLAG-MITO); or by amsacrine 100 mg/m2, days 2 to 4 (FLAG-AMSA).