Selected treatment options for patients not suitable for intensive chemotherapy*
| Regimen . | Recommended dosing . |
|---|---|
| Azacitidine or decitabine + venetoclax†,‡ | Azacitidine 75 mg/m2 SC/IV d1-7 (alternatively d1-5 + d8-9) or decitabine 20 mg/m2 IV d1-5; venetoclax dose ramp up: 100 mg d1, 200 mg d2, 400 mg PO QD d3-28 • Adjust venetoclax dose if concurrent strong CYP3A4 inhibitors: 10 mg on d1, 20 mg on d2, 50 mg on d3, 100 mg (or less‡) PO QD from d4 • For venetoclax dose modifications and management of myelosuppression see Table 12 |
| Low-dose cytarabine + venetoclax†,‡ | Cytarabine 20 mg/m2 SC daily, d1-10; venetoclax dose ramp up: 100 mg d1, 200 mg d2, 400 mg d3, 600 mg d4-28 PO • Adjust venetoclax dose if concurrent strong CYP3A4 inhibitors: 10 mg d1, 20 mg d2, 50 mg d3, 100 mg (or less‡) PO QD d4-28 • For venetoclax dose modifications and management of myelosuppression see Table 12 |
| Azacitidine + ivosidenib (AML with IDH1 mutation) | Azacitidine 75 mg/m2 SC/IV d1-7 (alternatively d1-5 + d8-9); ivosidenib 500 mg PO QD d1-28; both q4 wk, until progression |
| Ivosidenib (AML with IDH1 mutation) | For very frail patients, ivosidenib 500 mg PO QD d1-28 as monotherapy, until progression may be considered |
| Best supportive care | Including hydroxyurea; for patients who cannot tolerate any anti-leukemic therapy, or who do not wish any therapy |
| Regimen . | Recommended dosing . |
|---|---|
| Azacitidine or decitabine + venetoclax†,‡ | Azacitidine 75 mg/m2 SC/IV d1-7 (alternatively d1-5 + d8-9) or decitabine 20 mg/m2 IV d1-5; venetoclax dose ramp up: 100 mg d1, 200 mg d2, 400 mg PO QD d3-28 • Adjust venetoclax dose if concurrent strong CYP3A4 inhibitors: 10 mg on d1, 20 mg on d2, 50 mg on d3, 100 mg (or less‡) PO QD from d4 • For venetoclax dose modifications and management of myelosuppression see Table 12 |
| Low-dose cytarabine + venetoclax†,‡ | Cytarabine 20 mg/m2 SC daily, d1-10; venetoclax dose ramp up: 100 mg d1, 200 mg d2, 400 mg d3, 600 mg d4-28 PO • Adjust venetoclax dose if concurrent strong CYP3A4 inhibitors: 10 mg d1, 20 mg d2, 50 mg d3, 100 mg (or less‡) PO QD d4-28 • For venetoclax dose modifications and management of myelosuppression see Table 12 |
| Azacitidine + ivosidenib (AML with IDH1 mutation) | Azacitidine 75 mg/m2 SC/IV d1-7 (alternatively d1-5 + d8-9); ivosidenib 500 mg PO QD d1-28; both q4 wk, until progression |
| Ivosidenib (AML with IDH1 mutation) | For very frail patients, ivosidenib 500 mg PO QD d1-28 as monotherapy, until progression may be considered |
| Best supportive care | Including hydroxyurea; for patients who cannot tolerate any anti-leukemic therapy, or who do not wish any therapy |
For instance, criteria that have been used in clinical trials to select patients not suitable for intensive chemotherapy have been as follows: (1) age ≥75 y (however, this cannot be an absolute criterion; for instance, patients with more favorable disease and without relevant comorbidities may derive benefit from intensive chemotherapy) or (2) ECOG performance status > 2 and/or age-related comorbidities, such as severe cardiac disorder (eg, congestive heart failure requiring treatment, ejection fraction ≤ 50%, or chronic stable angina), severe pulmonary disorder (eg, DLCO ≤ 65% or FEV1 ≤ 65%), creatinine clearance < 45 mL/min, hepatic disorder with total bilirubin > 1.5 times the upper limit of normal, or any other comorbidity that the physician assesses to be incompatible with intensive chemotherapy.
To reduce the risk of tumor lysis syndrome, the prophylactic use of uric acid lowering drugs, close electrolyte monitoring and cytoreduction of the WBC to < 25 x 109/L or even lower, for patients with high bone marrow blast burden, elevated LDH is recommended.
In the VIALE-A and VIALE-C trials, an adjusted venetoclax dose of 50 mg was used in the presence of a strong CYP3A4 inhibitor. This venetoclax dose is supported by a pharmacokinetic study examining venetoclax in the presence of posaconazole.207