Table 2.
Selected ECIs
| ECIs | Incidence, % |
Exposure-adjusted incidence rate∗ |
AE burden score, mean (SD) |
|||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Any grade |
Grade ≥3 |
Any grade |
Grade ≥3 |
Grades 1-4 |
Grades 1-5 |
|||||||
| Acala n = 266 |
Ibru n = 263 |
Acala n = 266 |
Ibru n = 263 |
Acala n = 266 |
Ibru n = 263 |
Acala n = 266 |
Ibru n = 263 |
Acala n = 266 |
Ibru n = 263 |
Acala n = 266 |
Ibru n = 263 |
|
| Cardiac events overall† | 24 | 30 | 9 | 10 | 1.2 | 1.9 | 0.4 | 0.5 | 0.11 (0.355) | 0.26 (1.059) | 0.11 (0.354) | 0.26 (1.053) |
| Afib/flutter | 9 | 16‡ | 5 | 4 | 0.4 | 0.7 | 0.2 | 0.1 | 0.03 (0.187) | 0.08§(0.316) | 0.03 (0.187) | 0.08§(0.316) |
| HTN‖ | 9 | 23‡ | 4 | 9‡ | 0.4 | 1.2 | 0.1 | 0.4 | 0.07 (0.336) | 0.24§(0.682) | 0.07 (0.336) | 0.24§(0.682) |
| Bleeding events¶ | 38 | 51‡ | 4 | 5 | 2.4 | 3.8 | 0.1 | 0.2 | 0.15 (0.377) | 0.26§(0.568) | 0.18 (0.667) | 0.26§(0.568) |
| Major bleeding events# | 5∗∗ | 5†† | 4 | 5 | 0.2 | 0.2 | 0.1 | 0.2 | 0.02 (0.143) | 0.01 (0.153) | 0.05 (0.576) | 0.01 (0.153) |
| Infections‡‡ | 78 | 81 | 31 | 30 | 8.9 | 10.4 | 1.6 | 2.0 | 0.37 (1.056) | 0.36 (0.797) | 0.46 (1.513) | 0.41 (0.904) |
Acala, acalabrutinib; Afib/flutter, atrial fibrillation/flutter; CNS, central nervous system; HTN, hypertension; Ibru, ibrutinib.
Reported as events per 100 person-months.
Based on MedDRA cardiac system organ class terms.
2-sided P value < .05 without multiplicity adjustment, for comparison of incidence based on the Barnard exact test (indicated in bold).
2-sided P value < .05 without multiplicity adjustment based on Wilcoxon rank-sum test (indicated in bold). P value compares difference in overall distribution rather than mean score.
Includes HTN, blood pressure increase, and blood pressure systolic increase.
Bleeding events occurring in ≥10% of patients in either treatment arm include contusion and epistaxis.
Any hemorrhagic event that was serious, grade ≥3, or a CNS hemorrhage (any grade).
Of 12 patients with major bleeding events in the acalabrutinib arm, CNS-related hemorrhage events were reported in 4 patients (1 with subdural hematoma [grade 3], 2 with intracranial hemorrhage [grade 3 and grade 5], and 1 with cerebral hemorrhage [grade 2]).
Of 14 patients with major bleeding events in the ibrutinib arm, CNS-related hemorrhage events were reported in 1 patient who had both grade 1 subdural hematoma and grade 3 intracranial hemorrhage.
Infections occurring in ≥10% of patients in either treatment arm include upper respiratory tract infection, pneumonia, bronchitis, nasopharyngitis, and urinary tract infection.