Treatment-emergent AEs
| Event term, n (%) . | Ibrutinib (n = 98) . | Zanubrutinib (n = 101) . | ||
|---|---|---|---|---|
| All grade . | Grade ≥3 . | All grade . | Grade ≥3 . | |
| Nonhematologic AEs | ||||
| Diarrhea* | 31 (32) | 1 (1) | 21 (21) | 3 (3) |
| Upper respiratory tract infection | 28 (29) | 1 (1) | 24 (24) | 0 |
| Contusion* | 23 (24) | 0 | 13 (13) | 0 |
| Muscle spasms* | 23 (24) | 1 (1) | 10 (10) | 0 |
| Epistaxis | 19 (19) | 0 | 13 (13) | 0 |
| Peripheral edema* | 19 (19) | 0 | 9 (9) | 0 |
| Cough | 17 (17) | 0 | 13 (13) | 0 |
| Rash | 16 (16) | 0 | 13 (13) | 0 |
| Hypertension | 16 (16) | 11 (11) | 11 (11) | 6 (6) |
| Arthralgia | 16 (16) | 0 | 13 (13) | 3 (3) |
| Fatigue | 15 (15) | 1 (1) | 19 (19) | 1 (1) |
| Atrial fibrillation/flutter* | 15 (15) | 4 (4) | 2 (2) | 0 |
| Nausea | 13 (13) | 1 (1) | 15 (15) | 0 |
| Vomiting | 13 (13) | 1 (1) | 9 (9) | 0 |
| Pyrexia | 12 (12) | 2 (2) | 13 (13) | 2 (2) |
| Pneumonia* | 12 (12) | 7 (7) | 2 (2) | 1 (1) |
| Headache | 11 (11) | 1 (1) | 15 (15) | 1 (1) |
| Urinary tract infection | 10 (10) | 2 (2) | 10 (10) | 0 |
| Hematuria | 10 (10) | 2 (2) | 7 (7) | 0 |
| Dizziness | 9 (9) | 0 | 13 (13) | 0 |
| Constipation | 7 (7) | 0 | 16 (16) | 0 |
| Nasopharyngitis | 7 (7) | 0 | 11 (11) | 0 |
| Extremity pain | 7 (7) | 0 | 11 (11) | 1 (1) |
| Back pain | 6 (6) | 0 | 14 (14) | 4 (4) |
| Dyspnea | 6 (6) | 0 | 14 (14) | 0 |
| Hematologic AEs | ||||
| Neutropenia* | 13 (13) | 8 (8)† | 29 (29) | 19 (20)† |
| Febrile neutropenia | 0 | 0 | 4 (4) | 4 (4) |
| Thrombocytopenia | 10 (10) | 3 (3) | 10 (10) | 6 (6) |
| Anemia | 10 (10) | 5 (5) | 12 (12) | 5 (5) |
| Event term, n (%) . | Ibrutinib (n = 98) . | Zanubrutinib (n = 101) . | ||
|---|---|---|---|---|
| All grade . | Grade ≥3 . | All grade . | Grade ≥3 . | |
| Nonhematologic AEs | ||||
| Diarrhea* | 31 (32) | 1 (1) | 21 (21) | 3 (3) |
| Upper respiratory tract infection | 28 (29) | 1 (1) | 24 (24) | 0 |
| Contusion* | 23 (24) | 0 | 13 (13) | 0 |
| Muscle spasms* | 23 (24) | 1 (1) | 10 (10) | 0 |
| Epistaxis | 19 (19) | 0 | 13 (13) | 0 |
| Peripheral edema* | 19 (19) | 0 | 9 (9) | 0 |
| Cough | 17 (17) | 0 | 13 (13) | 0 |
| Rash | 16 (16) | 0 | 13 (13) | 0 |
| Hypertension | 16 (16) | 11 (11) | 11 (11) | 6 (6) |
| Arthralgia | 16 (16) | 0 | 13 (13) | 3 (3) |
| Fatigue | 15 (15) | 1 (1) | 19 (19) | 1 (1) |
| Atrial fibrillation/flutter* | 15 (15) | 4 (4) | 2 (2) | 0 |
| Nausea | 13 (13) | 1 (1) | 15 (15) | 0 |
| Vomiting | 13 (13) | 1 (1) | 9 (9) | 0 |
| Pyrexia | 12 (12) | 2 (2) | 13 (13) | 2 (2) |
| Pneumonia* | 12 (12) | 7 (7) | 2 (2) | 1 (1) |
| Headache | 11 (11) | 1 (1) | 15 (15) | 1 (1) |
| Urinary tract infection | 10 (10) | 2 (2) | 10 (10) | 0 |
| Hematuria | 10 (10) | 2 (2) | 7 (7) | 0 |
| Dizziness | 9 (9) | 0 | 13 (13) | 0 |
| Constipation | 7 (7) | 0 | 16 (16) | 0 |
| Nasopharyngitis | 7 (7) | 0 | 11 (11) | 0 |
| Extremity pain | 7 (7) | 0 | 11 (11) | 1 (1) |
| Back pain | 6 (6) | 0 | 14 (14) | 4 (4) |
| Dyspnea | 6 (6) | 0 | 14 (14) | 0 |
| Hematologic AEs | ||||
| Neutropenia* | 13 (13) | 8 (8)† | 29 (29) | 19 (20)† |
| Febrile neutropenia | 0 | 0 | 4 (4) | 4 (4) |
| Thrombocytopenia | 10 (10) | 3 (3) | 10 (10) | 6 (6) |
| Anemia | 10 (10) | 5 (5) | 12 (12) | 5 (5) |
| AEIs, events/100 person-months‡ . | Ibrutinib . | Zanubrutinib . | ||
|---|---|---|---|---|
| All grade . | Grade ≥3 . | All grade . | Grade ≥3 . | |
| Infections | 8.3 | 1.2 | 7.9 | 1.1 |
| Opportunistic infections | 0.1 | 0 | 0.1 | 0.1 |
| Bleeding | 7.0 | 0.5 | 4.4 | 0.3 |
| Major hemorrhage | 0.6 | 0.5 | 0.3 | 0.3 |
| Hypertension | 1.2 | 0.8 | 0.7 | 0.3 |
| Atrial fibrillation/flutter | 1.0 | 0.2 | 0.1 | 0 |
| Neutropenia | 0.9 | 0.5 | 2.1 | 1.3 |
| Thrombocytopenia | 0.8 | 0.2 | 0.6 | 0.3 |
| Second primary malignancies | 0.7 | 0.1 | 0.7 | 0.1 |
| Skin cancers | 0.6 | 0 | 0.5 | 0 |
| Anemia | 0.6 | 0.3 | 0.7 | 0.3 |
| Tumor lysis syndrome | 0 | 0 | 0 | 0 |
| AEIs, events/100 person-months‡ . | Ibrutinib . | Zanubrutinib . | ||
|---|---|---|---|---|
| All grade . | Grade ≥3 . | All grade . | Grade ≥3 . | |
| Infections | 8.3 | 1.2 | 7.9 | 1.1 |
| Opportunistic infections | 0.1 | 0 | 0.1 | 0.1 |
| Bleeding | 7.0 | 0.5 | 4.4 | 0.3 |
| Major hemorrhage | 0.6 | 0.5 | 0.3 | 0.3 |
| Hypertension | 1.2 | 0.8 | 0.7 | 0.3 |
| Atrial fibrillation/flutter | 1.0 | 0.2 | 0.1 | 0 |
| Neutropenia | 0.9 | 0.5 | 2.1 | 1.3 |
| Thrombocytopenia | 0.8 | 0.2 | 0.6 | 0.3 |
| Second primary malignancies | 0.7 | 0.1 | 0.7 | 0.1 |
| Skin cancers | 0.6 | 0 | 0.5 | 0 |
| Anemia | 0.6 | 0.3 | 0.7 | 0.3 |
| Tumor lysis syndrome | 0 | 0 | 0 | 0 |
Data are for treatment-emergent AEs in all cohort 1 patients. Listed events were reported in ≥10% of patients (all grade) or for grade ≥3, in ≥5% in either arm. Events are listed in descending order of frequency by all-grade incidence in the ibrutinib arm.
The difference in all-grade incidence between arms is ≥10%. P = .05, P = .005, and P = .02 for comparisons of all-grade diarrhea, muscle spasms, and peripheral edema, respectively. P = .0004 and P = .02 for the comparisons of all-grade and grade ≥3 atrial fibrillation, and P = .002 and P = .02 for all-grade and grade ≥3 pneumonia, respectively. All P values (1-sided, testing ibrutinib > zanubrutinib event rates) were calculated using Barnard’s exact test without adjustment for multiplicity.
Includes the Medical Dictionary for Regulatory Activities–preferred term “neutrophil count decreased” in 1 and 4 patients in the ibrutinib and zanubrutinib arms, respectively.
P = .08, P = .001, and P = .009 for the comparisons of all-grade bleeding, atrial fibrillation, and neutropenia, respectively. P = .05 and P = .03 for the comparisons of grade ≥3 atrial fibrillation and neutropenia, respectively. All P values are 2-sided without adjustment for multiplicity.38