AEs of special interest
| AEs . | R/I to imatinib or dasatinib (n = 33) . | Newly diagnosed (n = 25) . | All patients (N = 58) . | |||
|---|---|---|---|---|---|---|
| All grades . | Grade 3 to 4 . | All grades . | Grade 3 to 4 . | All grades . | Grade 3 to 4 . | |
| Cardiovascular events* or cardiac failure | 0 | 0 | 0 | 0 | 0 | 0 |
| Increased blood cholesterol† | 3 (9.1) | 0 | 2 (8.0) | 1 (4.0) | 5 (8.6) | 1 (1.7) |
| Increased blood glucose‡ | 2 (6.1) | 0 | 0 | 0 | 2 (3.4) | 0 |
| Fluid retention | 1 (3.0) | 0 | 3 (12.0) | 1 (4.0) | 4 (6.9) | 1 (1.7) |
| Edema and other fluid retention | 1 (3.0) | 0 | 3 (12.0) | 1 (4.0) | 4 (6.9) | 1 (1.7) |
| Medically severe fluid retention | 0 | 0 | 0 | 0 | 0 | 0 |
| Hepatotoxicity | 20 (60.6) | 8 (24.2) | 16 (64.0) | 6 (24.0) | 36 (62.1) | 14 (24.1) |
| Increased hepatic transaminase and bilirubin§ | 19 (57.6) | 7 (21.2) | 16 (64.0) | 6 (24.0) | 35 (60.3) | 13 (22.4) |
| Drug-induced liver injury|| | 1 (3.0) | 1 (3.0) | 0 | 0 | 1 (1.7) | 1 (1.7) |
| Myelosuppression (thrombocytopenia) | 1 (3.0) | 0 | 8 (32.0) | 3 (12.0) | 9 (15.5) | 3 (5.2) |
| Pancreatitis | 0 | 0 | 0 | 0 | 0 | 0 |
| QT prolongation¶ | 5 (15.2) | 0 | 3 (12.0) | 0 | 8 (13.8) | 0 |
| Rash | 15 (45.5) | 5 (12.2) | 15 (60.0) | 2 (8.0) | 30 (51.7) | 7 (12.1) |
| Renal events | 0 | 0 | 0 | 0 | 0 | 0 |
| Significant bleeding | 0 | 0 | 0 | 0 | 0 | 0 |
| AEs . | R/I to imatinib or dasatinib (n = 33) . | Newly diagnosed (n = 25) . | All patients (N = 58) . | |||
|---|---|---|---|---|---|---|
| All grades . | Grade 3 to 4 . | All grades . | Grade 3 to 4 . | All grades . | Grade 3 to 4 . | |
| Cardiovascular events* or cardiac failure | 0 | 0 | 0 | 0 | 0 | 0 |
| Increased blood cholesterol† | 3 (9.1) | 0 | 2 (8.0) | 1 (4.0) | 5 (8.6) | 1 (1.7) |
| Increased blood glucose‡ | 2 (6.1) | 0 | 0 | 0 | 2 (3.4) | 0 |
| Fluid retention | 1 (3.0) | 0 | 3 (12.0) | 1 (4.0) | 4 (6.9) | 1 (1.7) |
| Edema and other fluid retention | 1 (3.0) | 0 | 3 (12.0) | 1 (4.0) | 4 (6.9) | 1 (1.7) |
| Medically severe fluid retention | 0 | 0 | 0 | 0 | 0 | 0 |
| Hepatotoxicity | 20 (60.6) | 8 (24.2) | 16 (64.0) | 6 (24.0) | 36 (62.1) | 14 (24.1) |
| Increased hepatic transaminase and bilirubin§ | 19 (57.6) | 7 (21.2) | 16 (64.0) | 6 (24.0) | 35 (60.3) | 13 (22.4) |
| Drug-induced liver injury|| | 1 (3.0) | 1 (3.0) | 0 | 0 | 1 (1.7) | 1 (1.7) |
| Myelosuppression (thrombocytopenia) | 1 (3.0) | 0 | 8 (32.0) | 3 (12.0) | 9 (15.5) | 3 (5.2) |
| Pancreatitis | 0 | 0 | 0 | 0 | 0 | 0 |
| QT prolongation¶ | 5 (15.2) | 0 | 3 (12.0) | 0 | 8 (13.8) | 0 |
| Rash | 15 (45.5) | 5 (12.2) | 15 (60.0) | 2 (8.0) | 30 (51.7) | 7 (12.1) |
| Renal events | 0 | 0 | 0 | 0 | 0 | 0 |
| Significant bleeding | 0 | 0 | 0 | 0 | 0 | 0 |
Data are presented as number (%).
No events were reported in any of the cardiovascular event subgroups (ischemic cerebrovascular events, ischemic heart disease, peripheral arterial occlusive disease, or others).
One 10-year-old girl in the newly diagnosed cohort experienced a grade 3 increase in blood cholesterol requiring dose interruption for 26 days. Nilotinib was restarted while the patient had a mild increase in cholesterol (grade 1), and cholesterol improved to normal limits. None of the other events required dose adjustment or discontinuation.
None of these events required dose adjustment or discontinuation.
These events led to dose adjustments or interruptions in 11 patients in each cohort and discontinuation in 3 patients in each cohort.
Several episodes of grade 2 to 3 drug-induced liver injury were reported in 1 patient. Clinically, the episodes reflected increases in transaminase and bilirubin, and there were no signs of severe or progressive liver dysfunction.
Preferred terms for AEs in this group included electrocardiogram QT prolonged (n = 7) and syncope (n = 1; newly diagnosed cohort). In 6 of the 8 patients, these events were considered related to nilotinib. Three patients had newly occurring QTcF >450 ms on study, and 4 patients had newly occurring QTcF >480 ms in electrocardiograms performed per protocol; in the patient with syncope, QTcF was normal on the same date, and the physician considered the event to be unrelated to nilotinib. No episode of QTcF >500 ms or >60-ms increase from baseline occurred. In the R/I cohort, 3 of 5 patients with AEs of QT prolongation required dose adjustments or interruptions; none discontinued nilotinib. In the newly diagnosed cohort, 3 of 3 patients with AEs of QT prolongation required dose reductions or interruptions but not discontinuation. All AEs related to QT prolongation had resolved by the data cutoff.