Most Frequently Reported Drug-Related Adverse Events (No. of Patients)
| . | CMA-676 Dose (mg/m2) . | |||||||
|---|---|---|---|---|---|---|---|---|
| 0.25 . | 0.5 . | 1 . | 2 . | 4 . | 5 . | 6 . | 9 . | |
| Event* | (n = 4) | (n = 3) | (n = 4) | (n = 3) | (n = 6) | (n = 6) | (n = 8) | (n = 7) |
| Grade 0-I fever/chills | 4 | 2 | 1 | 1 | 4 | 1 | 3 | 3 |
| Grade II fever/chills | — | 1 | 3 | 2 | 2 | 5 | 3 | 3 |
| Grade III† fever/chills | — | — | — | — | — | — | 1‡ | 1 |
| Grade IV fever/chills | — | — | — | — | — | — | 12-153 | — |
| Grade III hepatic enzyme elevation (AST or ALT) | — | 1 | 1 | — | — | 4 | 1 | 1 |
| Grade IV hepatic enzyme elevation (AST or ALT) | — | — | — | — | — | — | 12-155 | — |
| . | CMA-676 Dose (mg/m2) . | |||||||
|---|---|---|---|---|---|---|---|---|
| 0.25 . | 0.5 . | 1 . | 2 . | 4 . | 5 . | 6 . | 9 . | |
| Event* | (n = 4) | (n = 3) | (n = 4) | (n = 3) | (n = 6) | (n = 6) | (n = 8) | (n = 7) |
| Grade 0-I fever/chills | 4 | 2 | 1 | 1 | 4 | 1 | 3 | 3 |
| Grade II fever/chills | — | 1 | 3 | 2 | 2 | 5 | 3 | 3 |
| Grade III† fever/chills | — | — | — | — | — | — | 1‡ | 1 |
| Grade IV fever/chills | — | — | — | — | — | — | 12-153 | — |
| Grade III hepatic enzyme elevation (AST or ALT) | — | 1 | 1 | — | — | 4 | 1 | 1 |
| Grade IV hepatic enzyme elevation (AST or ALT) | — | — | — | — | — | — | 12-155 | — |
Abbreviations: AST, alanine serum transaminase; ALT, alanine aminotransferase.
Grades are defined according to modified World Health Organization toxicity grading scale.
Modified to include fever <40°C with asymptomatic hypotension.
This patient (FH-007) is represented in the table twice. He experienced grade II fever/chills after his initial treatment at 1 mg/m2. He developed shortness of breath in association with retreatment with CMA-676 after his leukemia relapsed, presumably caused by an immune reaction to CMA-676.
This patient (COH-008) who had asymptomatic hypotension and was receiving low-dose dopamine before CMA-676 administration, had a temperature >40°C and reversible symptomatic hypotension 5 hours after the initiation of the CMA-676 infusion at 6 mg/m2.
This patient (FH-020) with documented concurrent cholelithiasis had a pretreatment AST of 13 U/L that increased to 304 U/L 4 days after receiving the first dose of CMA-676, and rapidly declined to the normal range within a week. Immediately before receipt of the second dose of CMA-676, her AST increased to 1,804 U/L and again rapidly returned to the normal range. Elevated enzymes were thought to be primarily due to the patient’s cholelithiasis.