Table 3.
Integrated safety analysis: frequency (by severity) of and outcomes with select AEs of clinical interest
| Diarrhea | Arthralgia | Fatigue | Atrial fibrillation | HTN* | Infection† | Rash* | Bleeding/bruising* | |
|---|---|---|---|---|---|---|---|---|
| Any-grade AE, n (% of all patients) | 173 (52) | 74 (22) | 119 (36) | 36 (11)‡ | 69 (21) | 274 (83) | 117 (35) | 182 (55)§ |
| Grade 1 | 116 (35) | 45 (14) | 65 (20) | 5 (2) | 11 (3) | 24 (7) | 74 (22) | 130 (39) |
| Grade 2 | 42 (13) | 22 (7) | 44 (13) | 14 (4) | 34 (10) | 149 (45) | 32 (10) | 35 (11) |
| Grade 3 | 15 (5) | 7 (2) | 10 (3) | 16 (5) | 24 (7) | 81 (25) | 11 (3) | 14 (4) |
| Grade 4 | 0 (0) | 0 (0) | 0 (0) | 0 (0) | 0 (0) | 12 (4) | 0 (0) | 2 (1) |
| Grade 5 | 0 (0) | 0 (0) | 0 (0) | 0 (0) | 0 (0) | 8 (2) | 0 (0) | 1 (<1) |
| AE management and resolution, n (% of patients with the AE) | ||||||||
| AE(s) resolved¶ | 157 (91) | 41 (55) | 67 (56) | 20 (56) | 25 (36) | 195 (71) | 89 (76) | 124 (68) |
| Received concomitant medication for management | 64 (37) | 45 (61) | 3 (3) | 30 (83) | 45 (65) | 257 (94) | 65 (56) | 41 (23) |
| Ibrutinib dose held for >7 d|| | 14 (8) | 3 (4) | 7 (6) | 7 (19) | 2 (3) | 50 (18) | 9 (8) | 20 (11) |
| Ibrutinib dose reduction | 5 (3) | 3 (4) | 2 (2) | 4 (11) | 0 (0) | 3 (1) | 3 (3) | 4 (2) |
| Ibrutinib discontinuation# | 2 (1) | 0 (0) | 1 (1) | 3 (8) | 1 (1) | 16 (6) | 2 (2) | 6 (3) |
| Median duration until resolution of AE(s),** d | 7 | 33 | 57 | 3 | 34 | 13 | 31 | 23 |
HTN, hypertension.
Pooled AE terms include multiple preferred terms relevant to the AE of interest.
System organ class.
AE severity grade was not reported for 1 patient with atrial fibrillation.
Twenty-one patients reported 25 major hemorrhage events, including grade 1 subdural hematoma (n = 1); grade 2 hyphema, subdural hematoma, and vitreous hemorrhage (n = 1 each); grade 3 hematuria (n = 3), postprocedural hemorrhage (n = 2), spontaneous hematoma (n = 2), subdural hematoma (n = 2), traumatic hematoma (n = 2), and ecchymosis, epistaxis, gastrointestinal hemorrhage, rectal hemorrhage, subarachnoid hematoma, subarachnoid hemorrhage, and vitreous hemorrhage (n = 1 each); grade 4 cerebral hemorrhage and subdural hematoma (n = 1 each); and grade 5 subdural hematoma (n = 1).
Resolved or resolved with sequelae, as assessed by the investigator. If patient had multiple AEs, then all AEs must have been deemed by the investigator to be resolved to be counted as resolved.
The onset of the missing dose event must have occurred on or ≤7 d after the related AE onset date.
Includes patients with any AEs contributing to treatment discontinuation.
Median event duration based on all resolved AEs.