BCL-2, hedgehog, and CD33-directed therapies: when to push through and when to stop
| Drug name . | Dose and frequency . | Toxicity . | When to push through . | When to stop drug . |
|---|---|---|---|---|
| Venetoclax/HMAs (azacitidine or decitabine) or low-dose cytarabine23,47 | 400 mg orally once per day (azacitidine or decitabine) or 600 mg orally once per day (low-dose cytarabine) | Myelosuppression, tumor lysis, neutropenia, anemia, thrombocytopenia | First 2 cycles result in mild to moderate renal dysfunction, hepatotoxicity, cytopenias | Reduce dose by 50% for severe liver impairment (Child-Pugh score for cirrhosis). Hold if bone marrow evaluation on days 21 to 28 shows cytoreduction (<5% blasts). In responding patients, consider truncating duration of venetoclax therapy to 7 to 21 days in subsequent cycles; discontinue after 2 to 4 cycles if there is no response. |
| Glasdegib/low-dose cytarabine 20 mg subcutaneously twice per day × 10 days34 | 100 mg orally once per day | Fatigue, febrile neutropenia, dyspnea, anemia, dysgeusia, anorexia, QTc prolongation | Dysgeusia, fatigue, myalgias, cytopenias, QTc 480-500 ms during the first 6 cycles | Hold for QTc prolongation >500 ms and resume at 50 mg; discontinue for life-threatening cardiac arrythmias, or 30 days before donating blood, or for ANC <500 cells per μL and/or platelets <10 000/μL for >42 days in the absence of disease progression, or after 6 cycles of therapy if there is no response. |
| Gemtuzumab ozogamicin plus 7+3 therapy and consolidation (favorable- or intermediate-risk AML)37,48 | 3 mg/m2 (maximum, 4.5 mg/m2) intravenous infusion on days 1,4, and 7 of cycle 1 induction | Liver dysfunction, VOD/SOS, fever, myelosuppression, infusion reactions | Induction and consolidation for favorable- or intermediate-risk AML, mild or moderate hepatotoxicity, myelosuppression, or mild or moderate infusion reaction | Hold or discontinue gemtuzumab ozogamicin for severe hepatotoxicity or bleeding. Discontinue gemtuzumab ozogamicin for VOD/SOS or life-threatening anaphylaxis, or at least 2 months before planned allo-SCT. |
| Drug name . | Dose and frequency . | Toxicity . | When to push through . | When to stop drug . |
|---|---|---|---|---|
| Venetoclax/HMAs (azacitidine or decitabine) or low-dose cytarabine23,47 | 400 mg orally once per day (azacitidine or decitabine) or 600 mg orally once per day (low-dose cytarabine) | Myelosuppression, tumor lysis, neutropenia, anemia, thrombocytopenia | First 2 cycles result in mild to moderate renal dysfunction, hepatotoxicity, cytopenias | Reduce dose by 50% for severe liver impairment (Child-Pugh score for cirrhosis). Hold if bone marrow evaluation on days 21 to 28 shows cytoreduction (<5% blasts). In responding patients, consider truncating duration of venetoclax therapy to 7 to 21 days in subsequent cycles; discontinue after 2 to 4 cycles if there is no response. |
| Glasdegib/low-dose cytarabine 20 mg subcutaneously twice per day × 10 days34 | 100 mg orally once per day | Fatigue, febrile neutropenia, dyspnea, anemia, dysgeusia, anorexia, QTc prolongation | Dysgeusia, fatigue, myalgias, cytopenias, QTc 480-500 ms during the first 6 cycles | Hold for QTc prolongation >500 ms and resume at 50 mg; discontinue for life-threatening cardiac arrythmias, or 30 days before donating blood, or for ANC <500 cells per μL and/or platelets <10 000/μL for >42 days in the absence of disease progression, or after 6 cycles of therapy if there is no response. |
| Gemtuzumab ozogamicin plus 7+3 therapy and consolidation (favorable- or intermediate-risk AML)37,48 | 3 mg/m2 (maximum, 4.5 mg/m2) intravenous infusion on days 1,4, and 7 of cycle 1 induction | Liver dysfunction, VOD/SOS, fever, myelosuppression, infusion reactions | Induction and consolidation for favorable- or intermediate-risk AML, mild or moderate hepatotoxicity, myelosuppression, or mild or moderate infusion reaction | Hold or discontinue gemtuzumab ozogamicin for severe hepatotoxicity or bleeding. Discontinue gemtuzumab ozogamicin for VOD/SOS or life-threatening anaphylaxis, or at least 2 months before planned allo-SCT. |
VOD/SOS, veno-occlusive disease/ sinusoidal obstructive syndrome; HMAs, hypomethylating agents; alloSCT, allogeneic stem cell transplant