IDH inhibitors: when to push through and when to stop
| Drug name . | Dose and frequency . | Toxicity . | When to push through . | When to stop . |
|---|---|---|---|---|
| Ivosidenib32 | 500 mg orally once per day | DS, QTc prolongation, cytopenias, high WBC | First 6 months, mild to moderate renal and hepatic dysfunction, and mild DS | Hold for severe DS with cardiopulmonary compromise that requires emergent hospitalization with or without renal dysfunction, for QTc prolongation >480 ms (resume when <480 ms). Discontinue for life-threatening cardiac arrythmias, for Guillain-Barré syndrome, or if there is no response (hematologic recovery/blast clearance) after 6 months. |
| Enasidenib33 | 100 mg orally once per day | DS, elevated bilirubin, cytopenias, high WBC | First 6 cycles, mild to moderate renal impairment, mild DS, bilirubin <3× ULN | Hold for severe DS with cardiopulmonary compromise requiring emergent hospitalization with or without renal dysfunction, for bilirubin 3× ULN or more and reduce dose to 50 mg once per day. Discontinue if there is no response (hematologic recovery or blast clearance) after 6 months. |
| Drug name . | Dose and frequency . | Toxicity . | When to push through . | When to stop . |
|---|---|---|---|---|
| Ivosidenib32 | 500 mg orally once per day | DS, QTc prolongation, cytopenias, high WBC | First 6 months, mild to moderate renal and hepatic dysfunction, and mild DS | Hold for severe DS with cardiopulmonary compromise that requires emergent hospitalization with or without renal dysfunction, for QTc prolongation >480 ms (resume when <480 ms). Discontinue for life-threatening cardiac arrythmias, for Guillain-Barré syndrome, or if there is no response (hematologic recovery/blast clearance) after 6 months. |
| Enasidenib33 | 100 mg orally once per day | DS, elevated bilirubin, cytopenias, high WBC | First 6 cycles, mild to moderate renal impairment, mild DS, bilirubin <3× ULN | Hold for severe DS with cardiopulmonary compromise requiring emergent hospitalization with or without renal dysfunction, for bilirubin 3× ULN or more and reduce dose to 50 mg once per day. Discontinue if there is no response (hematologic recovery or blast clearance) after 6 months. |
DS, differentiation syndrome; ULN, upper limit of normal; WBC, white blood cell count