Toxicities of AML therapies by organ system
| Toxicity . | Responsible drug(s) . | Description . | Treatment of toxicity . | When to stop drug . |
|---|---|---|---|---|
| Hepatotoxicity | Gemtuzumab ozogamicin | VOD/SOS, elevated AST, ALT, bilirubin | Monitor liver function test results frequently, use ursodiol, avoid administration in patients with known hepatic dysfunction, use defibrotide for VOD/SOS | Hold or discontinue gemtuzumab ozogamicin for severe hepatotoxicity; discontinue for VOD/SOS and at least 2 months before planned allo-SCT. |
| Enasidenib | Asymptomatic elevation of indirect bilirubin | Dose reduce to 50 mg once per day | No need to stop drug. | |
| Venetoclax | Elevated liver enzymes, bilirubin | Supportive care with no dose reduction | Reduce dose by 50% for severe liver impairment (Child-Pugh score for cirrhosis). | |
| Gilteritinib | Elevated liver function tests (transaminases, bilirubin), pancreatitis | Hold for elevated liver function tests (AST and ALT >5× ULN, bilirubin >3× ULN) and restart at 80 mg once per day | Hold for elevated liver function tests (AST and ALT >5× ULN, bilirubin >3× ULN) and restart at 80 mg once per day; hold drug for pancreatitis. | |
| Nephrotoxicity | Venetoclax + chemotherapy | Tumor lysis syndrome | Allopurinol, intravenous hydration, tumor lysis laboratory tests, frequent monitoring | Severe renal dysfunction in setting of tumor lysis. |
| Embryo-fetal toxicity | Glasdegib | Embryo-fetal toxicity | Withhold therapy in all individuals suspected of being pregnant, contraceptives | Do not give to individuals who are pregnant or breastfeeding; do not give blood within 30 days of last dose. |
| Neurologic complications | Glasdegib | Fatigue (asthenia), ageusia/dysgeusia (loss or alteration of sense of taste), anorexia, myalgias | Symptomatic measures, nonsteroidal anti-inflammatory drugs, zinc lozenges, analgesics | Hold for significant debilitating weight loss. |
| Gilteritinib | Posterior reversible encephalopathy syndrome | MRI scans, antiseizure medications | Permanently discontinue drug. | |
| Ivosidenib | Guillain-Barré syndrome | Lumbar puncture, MRI, ventilatory support | Permanently discontinue drug. | |
| Cardiotoxicity | Glasdegib | QTc prolongation | Perform ECGs before, and 1 week after intitation of therapy, and monthly for 2 months, supplement electrolytes, adjust other medications | Hold for significant QTC prolongation or development of cardiac arrhythmias. Reduce dose to 50 mg once per day, and discontinue for life-threatening cardiac arrythmias. |
| Midostaurin | QTc prolongation | ECGs once per week, electrolytes, substitute other medications | Hold for significant QTC prolongation or development of cardiac arrhythmias (dose related) per clinical trial. | |
| Gilteritinib | Orthostatic hypotension | Intravenous fluids, adjust blood pressure medications, add midodrine and/or fludrocortisone | Hold for severe symptomatic orthostasis. | |
| Gilteritinib | QTc prolongation | Electrolyte supplementation, baseline ECGs before cycle 1, on days 8 and 15, and start of cycles 2 and 3 | Hold for QTc prolongation >500 ms. | |
| Ivosidenib | QTc prolongation | Electrolyte supplementation, adjust other medications, ECG at baseline and once per week for 3 weeks, then once per month during treatment | Hold for significant QTC prolongation >500 ms or development of cardiac arrhythmias; reduce dose to 250 mg once per day. | |
| Gastrointestinal toxicity | Midostaurin 50 mg twice per day × 14 days | Nausea, vomiting, diarrhea, mucositis | Antiemetics before each dose, take with food, air each tablet outside of blister pack, rule out gastrointestinal infection, make up missed doses | Discontinue for life-threatening cardiac and peripheral vascular events. |
| Glasdegib | Ageusia/dysgeusia (loss or alteration of sense of taste), anorexia | Symptomatic measures, nonsteroidal anti-inflammatory drugs, zinc lozenges, analgesics | Hold for significant debilitating weight loss. | |
| Pulmonary toxicity | Gilteritinib | DS (2-75 days) | Dexamethasone intravenously or orally, oxygen, respiratory support, hydroxyurea, leukopheresis | Severe DS with life-threatening complications or no improvement after 48 hours of steroid treatment. |
| Ivosidenib | DS (1-86 days) | Dexamethasone intravenously or orally, oxygen, respiratory support, hydroxyurea, leukopheresis | Severe DS with life-threatening complications or no improvement after 48 hours of steroid treatment. | |
| Enasidenib | DS (1-86 days) | Dexamethasone intravenously or orally, oxygen, respiratory support, hydroxyurea, leukopheresis | Severe DS with life-threatening complications or no improvement after 48 hours of steroid treatment. | |
| Midostaurin | Drug-related interstitial pneumonia | Consider baseline chest CT before therapy, and rule out infections | Discontinue drug. | |
| Venetoclax + chemotherapy | Respiratory infections, pneumonia, | Consider baseline chest CT, Infectious Disease consult, antibiotics, antifungals, fungal markers | Do not stop drug during cycle 1 until bone marrow evaluation is complete. | |
| Hematologic toxicity | Venetoclax + chemotherapy | Prolonged myelosuppression | Daily transfusion support, neutropenic prophylaxis | Hold if cycle 1 days 21 to 28 bone marrow evaluation shows cytoreduction (<5% blasts), consider truncating duration of venetoclax therapy to 7-21 d in subsequent cycles. |
| Glasdegib | Prolonged myelosuppression | Transfusion support, neutropenic prophylaxis | Discontinue for ANC <500 cells per μL and/or platelets <10 000/μL for >42 days in the absence of disease progression. | |
| Gemtuzumab ozogamicin | Prolonged thrombocytopenia with risk of severe hemorrhages | Transfusion support, monitor counts once per week with frequent platelet transfusions, and take precautions to avoid falls | Hold or discontinue gemtuzumab ozogamicin for severe bleeding. | |
| Immunologic toxicity | Gemtuzumab ozogamicin | Infusion reaction before and 24 hours after dosing | Premedication (acetaminophen, diphenhydramine, corticosteroid) before each dose, frequent vital signs, clinical monitoring | Discontinue gemtuzumab ozogamicin for life-threatening anaphylaxis. |
| Toxicity . | Responsible drug(s) . | Description . | Treatment of toxicity . | When to stop drug . |
|---|---|---|---|---|
| Hepatotoxicity | Gemtuzumab ozogamicin | VOD/SOS, elevated AST, ALT, bilirubin | Monitor liver function test results frequently, use ursodiol, avoid administration in patients with known hepatic dysfunction, use defibrotide for VOD/SOS | Hold or discontinue gemtuzumab ozogamicin for severe hepatotoxicity; discontinue for VOD/SOS and at least 2 months before planned allo-SCT. |
| Enasidenib | Asymptomatic elevation of indirect bilirubin | Dose reduce to 50 mg once per day | No need to stop drug. | |
| Venetoclax | Elevated liver enzymes, bilirubin | Supportive care with no dose reduction | Reduce dose by 50% for severe liver impairment (Child-Pugh score for cirrhosis). | |
| Gilteritinib | Elevated liver function tests (transaminases, bilirubin), pancreatitis | Hold for elevated liver function tests (AST and ALT >5× ULN, bilirubin >3× ULN) and restart at 80 mg once per day | Hold for elevated liver function tests (AST and ALT >5× ULN, bilirubin >3× ULN) and restart at 80 mg once per day; hold drug for pancreatitis. | |
| Nephrotoxicity | Venetoclax + chemotherapy | Tumor lysis syndrome | Allopurinol, intravenous hydration, tumor lysis laboratory tests, frequent monitoring | Severe renal dysfunction in setting of tumor lysis. |
| Embryo-fetal toxicity | Glasdegib | Embryo-fetal toxicity | Withhold therapy in all individuals suspected of being pregnant, contraceptives | Do not give to individuals who are pregnant or breastfeeding; do not give blood within 30 days of last dose. |
| Neurologic complications | Glasdegib | Fatigue (asthenia), ageusia/dysgeusia (loss or alteration of sense of taste), anorexia, myalgias | Symptomatic measures, nonsteroidal anti-inflammatory drugs, zinc lozenges, analgesics | Hold for significant debilitating weight loss. |
| Gilteritinib | Posterior reversible encephalopathy syndrome | MRI scans, antiseizure medications | Permanently discontinue drug. | |
| Ivosidenib | Guillain-Barré syndrome | Lumbar puncture, MRI, ventilatory support | Permanently discontinue drug. | |
| Cardiotoxicity | Glasdegib | QTc prolongation | Perform ECGs before, and 1 week after intitation of therapy, and monthly for 2 months, supplement electrolytes, adjust other medications | Hold for significant QTC prolongation or development of cardiac arrhythmias. Reduce dose to 50 mg once per day, and discontinue for life-threatening cardiac arrythmias. |
| Midostaurin | QTc prolongation | ECGs once per week, electrolytes, substitute other medications | Hold for significant QTC prolongation or development of cardiac arrhythmias (dose related) per clinical trial. | |
| Gilteritinib | Orthostatic hypotension | Intravenous fluids, adjust blood pressure medications, add midodrine and/or fludrocortisone | Hold for severe symptomatic orthostasis. | |
| Gilteritinib | QTc prolongation | Electrolyte supplementation, baseline ECGs before cycle 1, on days 8 and 15, and start of cycles 2 and 3 | Hold for QTc prolongation >500 ms. | |
| Ivosidenib | QTc prolongation | Electrolyte supplementation, adjust other medications, ECG at baseline and once per week for 3 weeks, then once per month during treatment | Hold for significant QTC prolongation >500 ms or development of cardiac arrhythmias; reduce dose to 250 mg once per day. | |
| Gastrointestinal toxicity | Midostaurin 50 mg twice per day × 14 days | Nausea, vomiting, diarrhea, mucositis | Antiemetics before each dose, take with food, air each tablet outside of blister pack, rule out gastrointestinal infection, make up missed doses | Discontinue for life-threatening cardiac and peripheral vascular events. |
| Glasdegib | Ageusia/dysgeusia (loss or alteration of sense of taste), anorexia | Symptomatic measures, nonsteroidal anti-inflammatory drugs, zinc lozenges, analgesics | Hold for significant debilitating weight loss. | |
| Pulmonary toxicity | Gilteritinib | DS (2-75 days) | Dexamethasone intravenously or orally, oxygen, respiratory support, hydroxyurea, leukopheresis | Severe DS with life-threatening complications or no improvement after 48 hours of steroid treatment. |
| Ivosidenib | DS (1-86 days) | Dexamethasone intravenously or orally, oxygen, respiratory support, hydroxyurea, leukopheresis | Severe DS with life-threatening complications or no improvement after 48 hours of steroid treatment. | |
| Enasidenib | DS (1-86 days) | Dexamethasone intravenously or orally, oxygen, respiratory support, hydroxyurea, leukopheresis | Severe DS with life-threatening complications or no improvement after 48 hours of steroid treatment. | |
| Midostaurin | Drug-related interstitial pneumonia | Consider baseline chest CT before therapy, and rule out infections | Discontinue drug. | |
| Venetoclax + chemotherapy | Respiratory infections, pneumonia, | Consider baseline chest CT, Infectious Disease consult, antibiotics, antifungals, fungal markers | Do not stop drug during cycle 1 until bone marrow evaluation is complete. | |
| Hematologic toxicity | Venetoclax + chemotherapy | Prolonged myelosuppression | Daily transfusion support, neutropenic prophylaxis | Hold if cycle 1 days 21 to 28 bone marrow evaluation shows cytoreduction (<5% blasts), consider truncating duration of venetoclax therapy to 7-21 d in subsequent cycles. |
| Glasdegib | Prolonged myelosuppression | Transfusion support, neutropenic prophylaxis | Discontinue for ANC <500 cells per μL and/or platelets <10 000/μL for >42 days in the absence of disease progression. | |
| Gemtuzumab ozogamicin | Prolonged thrombocytopenia with risk of severe hemorrhages | Transfusion support, monitor counts once per week with frequent platelet transfusions, and take precautions to avoid falls | Hold or discontinue gemtuzumab ozogamicin for severe bleeding. | |
| Immunologic toxicity | Gemtuzumab ozogamicin | Infusion reaction before and 24 hours after dosing | Premedication (acetaminophen, diphenhydramine, corticosteroid) before each dose, frequent vital signs, clinical monitoring | Discontinue gemtuzumab ozogamicin for life-threatening anaphylaxis. |
MRI, magnetic resonance imaging; DS, differentiation syndrome; VOD/SOS, veno-occlusive disease/sinusoidal obstructive syndrome.