FLT3 inhibitors: when to push through and when to stop
| Drug name . | Dose and frequency . | Toxicity . | When to push through . | When to stop . |
|---|---|---|---|---|
| Midostaurin9,11 | 50 mg orally twice per day on days 8-21 of 7+3 treatment and high-dose cytarabine consolidation | Pneumonitis, nausea/vomiting, diarrhea, fever, mucositis, infections, cardiac issues (in patients age 60 to 70 years) | Complete 14-day regimen during induction and consolidation | Unable to take oral medication because of nausea/vomiting or development of life-threatening cardiac issues; discontinue for possibly drug-related interstitial pneumonitis without infectious etiology or if there is evidence of R/R disease. |
| Gilteritinib7 | 120 mg orally once per day | Liver dysfunction, fever, PRES, DS, myalgia/arthralgia, fatigue, edema | First 6 cycles of therapy, mild to moderate renal impairment, mild DS responding to therapy | Severe DS with life-threatening complications or no improvement after 48 hours of steroid therapy; elevated liver function tests (AST and ALT >5× ULN, bilirubin >3× ULN). Restart at 80 mg; if pancreatitis is present, restart at 80 mg. QTcF >500 ms (1%), adjust medications and restart at 80-120 mg. Discontinue for PRES (1%) or if there is no response after 6 cycles. |
| Sunitinib21 * | 50 mg once per day for 4 weeks with 1 to 2 weeks off the drug | Edema, fatigue, oral ulcerations, decreased appetite, headache, gastrointestinal symptoms | Not recommended for AML therapy | Not recommended for AML therapy at this time. |
| Sorafenib19,46 * | 200-400 mg orally twice per day | Skin rash, fatigue, diarrhea, liver, myalgias, marrow hypoplasia, cytopenia | Off-label use for mutant FLT3-ITD AML in combination with other HMAs | Hold for excessive bleeding and severe cytopenias (consider resuming dose at 200 mg); hold or discontinue drug for severe persistent hypertension or cardiac ischemia or infarction; discontinue for severe skin reactions or if there is no response in 3 months. |
| Ponatinib22 * | 45 mg orally once per day | Pancreatitis, petechiae | Off label use | Hold drug for pancreatitis and resume at lower dose (30 mg); discontinue for life-threatening cardiac and peripheral vascular events. |
| Quizartinib18 † | 30-60 mg orally once per day | QTcF prolongation (dose related), DS | Per clinical trial only | Hold for significant QTC prolongation or development of cardiac arrhythmias (dose related) per clinical trial or for severe DS with life-threatening complications or no improvement after 48 hours of steroid treatment. |
| Crenolanib17 † | 100 mg orally three times per day plus induction/consolidation or salvage | Nausea, vomiting, transaminitis, fluid retention, gastrointestinal bleeding | Per clinical trial only | Hold for gastrointestinal bleeding or toxicity and consider dose reduction (80 mg three times per day) per clinical trial. |
| Drug name . | Dose and frequency . | Toxicity . | When to push through . | When to stop . |
|---|---|---|---|---|
| Midostaurin9,11 | 50 mg orally twice per day on days 8-21 of 7+3 treatment and high-dose cytarabine consolidation | Pneumonitis, nausea/vomiting, diarrhea, fever, mucositis, infections, cardiac issues (in patients age 60 to 70 years) | Complete 14-day regimen during induction and consolidation | Unable to take oral medication because of nausea/vomiting or development of life-threatening cardiac issues; discontinue for possibly drug-related interstitial pneumonitis without infectious etiology or if there is evidence of R/R disease. |
| Gilteritinib7 | 120 mg orally once per day | Liver dysfunction, fever, PRES, DS, myalgia/arthralgia, fatigue, edema | First 6 cycles of therapy, mild to moderate renal impairment, mild DS responding to therapy | Severe DS with life-threatening complications or no improvement after 48 hours of steroid therapy; elevated liver function tests (AST and ALT >5× ULN, bilirubin >3× ULN). Restart at 80 mg; if pancreatitis is present, restart at 80 mg. QTcF >500 ms (1%), adjust medications and restart at 80-120 mg. Discontinue for PRES (1%) or if there is no response after 6 cycles. |
| Sunitinib21 * | 50 mg once per day for 4 weeks with 1 to 2 weeks off the drug | Edema, fatigue, oral ulcerations, decreased appetite, headache, gastrointestinal symptoms | Not recommended for AML therapy | Not recommended for AML therapy at this time. |
| Sorafenib19,46 * | 200-400 mg orally twice per day | Skin rash, fatigue, diarrhea, liver, myalgias, marrow hypoplasia, cytopenia | Off-label use for mutant FLT3-ITD AML in combination with other HMAs | Hold for excessive bleeding and severe cytopenias (consider resuming dose at 200 mg); hold or discontinue drug for severe persistent hypertension or cardiac ischemia or infarction; discontinue for severe skin reactions or if there is no response in 3 months. |
| Ponatinib22 * | 45 mg orally once per day | Pancreatitis, petechiae | Off label use | Hold drug for pancreatitis and resume at lower dose (30 mg); discontinue for life-threatening cardiac and peripheral vascular events. |
| Quizartinib18 † | 30-60 mg orally once per day | QTcF prolongation (dose related), DS | Per clinical trial only | Hold for significant QTC prolongation or development of cardiac arrhythmias (dose related) per clinical trial or for severe DS with life-threatening complications or no improvement after 48 hours of steroid treatment. |
| Crenolanib17 † | 100 mg orally three times per day plus induction/consolidation or salvage | Nausea, vomiting, transaminitis, fluid retention, gastrointestinal bleeding | Per clinical trial only | Hold for gastrointestinal bleeding or toxicity and consider dose reduction (80 mg three times per day) per clinical trial. |