Toxicity management for antibody therapy in ALL
| Antibody . | Toxicity . | Symptoms . | Management . |
|---|---|---|---|
| IO | Transaminitis | Jaundice | Grade ≥2: Interrupt IO dosing until recovery of total bilirubin to ≤1.5× ULN and AST/ALT to ≤2.5× ULN prior to each dose unless due to Gilbert syndrome or hemolysis |
| Hyperbilirubinemia | Right upper quadrant abdominal pain | ||
| IO | VOD | Jaundice | Early detection |
| Hepatomegaly | Supportive care with diuretics and oxygen | ||
| Right upper quadrant abdominal pain | Start defibrotide 6.25 mg/kg every 6 h immediately for 21-60 d until symptoms resolve | ||
| Edema | Discontinue IO permanently for all grades of VOD. | ||
| Ascites | |||
| Rapid weight gain | |||
| Blinatumomab | CRS | Fever, chills, hypotension, hypoxia, end-organ damage | Grade 1: Interrupt blinatumomab if fever does not resolve with acetaminophen |
| Grade 2-3: Interrupt blinatumomab if patient cannot be supported effectively with IV fluids (requires vasopressors) and/or nasal canula oxygen. Severe cases can be treated with tocilizumab if insufficient response with interrupting blinatumomab. | |||
| If symptoms resolve, patient may be rechallenged with blinatumomab at starting 9-μg/d dose. Escalate to 28 μg/d after 7 d if the toxicity does not recur. | |||
| Grade 4: Discontinue blinatumomab permanently. | |||
| Blinatumomab | Neurologic events | Delirium, encephalopathy, aphasia, somnolence, tremor, seizure | Grade 3: Withhold blinatumomab until grade ≤1 and for |
| at least 3 d, then restart | |||
| blinatumomab at 9 μg/d. | |||
| Escalate to 28 μg/d after | |||
| 7 d if the toxicity does not | |||
| recur. If the toxicity occurred at | |||
| 9 μg/d, or if the toxicity takes | |||
| >7 d to resolve, | |||
| discontinue blinatumomab permanently. | |||
| Tocilizumab will not cross the blood–brain barrier and has no utility | |||
| Grade 4: Discontinue blinatumomab permanently for seizure or other event. |
| Antibody . | Toxicity . | Symptoms . | Management . |
|---|---|---|---|
| IO | Transaminitis | Jaundice | Grade ≥2: Interrupt IO dosing until recovery of total bilirubin to ≤1.5× ULN and AST/ALT to ≤2.5× ULN prior to each dose unless due to Gilbert syndrome or hemolysis |
| Hyperbilirubinemia | Right upper quadrant abdominal pain | ||
| IO | VOD | Jaundice | Early detection |
| Hepatomegaly | Supportive care with diuretics and oxygen | ||
| Right upper quadrant abdominal pain | Start defibrotide 6.25 mg/kg every 6 h immediately for 21-60 d until symptoms resolve | ||
| Edema | Discontinue IO permanently for all grades of VOD. | ||
| Ascites | |||
| Rapid weight gain | |||
| Blinatumomab | CRS | Fever, chills, hypotension, hypoxia, end-organ damage | Grade 1: Interrupt blinatumomab if fever does not resolve with acetaminophen |
| Grade 2-3: Interrupt blinatumomab if patient cannot be supported effectively with IV fluids (requires vasopressors) and/or nasal canula oxygen. Severe cases can be treated with tocilizumab if insufficient response with interrupting blinatumomab. | |||
| If symptoms resolve, patient may be rechallenged with blinatumomab at starting 9-μg/d dose. Escalate to 28 μg/d after 7 d if the toxicity does not recur. | |||
| Grade 4: Discontinue blinatumomab permanently. | |||
| Blinatumomab | Neurologic events | Delirium, encephalopathy, aphasia, somnolence, tremor, seizure | Grade 3: Withhold blinatumomab until grade ≤1 and for |
| at least 3 d, then restart | |||
| blinatumomab at 9 μg/d. | |||
| Escalate to 28 μg/d after | |||
| 7 d if the toxicity does not | |||
| recur. If the toxicity occurred at | |||
| 9 μg/d, or if the toxicity takes | |||
| >7 d to resolve, | |||
| discontinue blinatumomab permanently. | |||
| Tocilizumab will not cross the blood–brain barrier and has no utility | |||
| Grade 4: Discontinue blinatumomab permanently for seizure or other event. |
ALT, alanine aminotransferase; AST, aspartate transaminase; ULN, upper limit of normal.