CONSISTENT SAFETY ACROSS
LINES OF THERAPY
First Line
Sequoia (Study 304)
COHORT 1: OVERALL INCIDENCE OF ADVERSE REACTIONS (ARs)1,2
| Adverse Reactions | ARs in ≥10% of Patients Without Del(17p) | Pooled Safety Population* | ||||
|---|---|---|---|---|---|---|
| BRUKINSA (n=240) | BR (n=227) | BRUKINSA (N=1550) | ||||
| All Grades (%) | Grade ≥3 (%) | All Grades (%) | Grade ≥3 (%) | All Grades (%) | Grade ≥3 (%) | |
| Musculoskeletal pain | 33 | 2 | 17 | 0.4 | 30 | 2 |
| Upper respiratory tract infection | 28 | 1 | 15 | 0.9 | 39 | 2 |
| Pneumonia | 13† | 5 | 8‡ | 4 | 20 | 11 |
| Hemorrhage | 27† | 4 | 4 | 0.4 | 30 | 4 |
| Hypertension | 14 | 7 | 5 | 3 | 14 | 7 |
| Rash | 24 | 1 | 30 | 5 | 28 | 0.9 |
| Bruising | 24 | 0 | 3 | 0 | 23 | 0.1 |
| Cough | 15 | 0 | 10 | 0 | 19 | 0.1 |
| Diarrhea | 14 | 0.8 | 12‡ | 0.9 | 19 | 2 |
| Constipation | 10 | 0.4 | 18 | 0 | 13 | 0.3 |
| Nausea | 10 | 0 | 33 | 1 | 11 | 0.2 |
| Fatigue | 14 | 1 | 21 | 2 | 17 | 1 |
| Second primary malignancy | 13† | 6 | 1 | 0.4 | 13 | 6 |
| Headache | 12 | 0 | 8 | 0 | 11 | 0.4 |
| Dizziness | 11 | 0.8 | 5 | 0 | 11 | 0.3 |
*Includes chronic lymphocytic leukemia, Waldenström’s macroglobulinemia, mantle cell lymphoma, follicular lymphoma, marginal zone lymphoma, hairy cell leukemia, diffuse large B-cell lymphoma, and Richter’s transformation.2
†Includes 3 fatal outcomes.1
‡Includes 2 fatal outcomes.1
Sequoia (Study 304)
COHORT 2: OVERALL INCIDENCE OF ARs1,2
| Adverse Reactions | ARs in ≥10% of Patients With Del(17p) | Pooled Safety Population* | ||
|---|---|---|---|---|
| BRUKINSA (n=111) | BRUKINSA (N=1550) | |||
| All Grades (%) | Grade ≥3 (%) | All Grades (%) | Grade ≥3 (%) | |
| Upper respiratory tract infection | 38 | 0 | 39 | 2 |
| Pneumonia | 20† | 8 | 20 | 11 |
| Musculoskeletal pain | 38 | 3 | 30 | 2 |
| Rash | 28 | 0 | 28 | 0.9 |
| Bruising | 26 | 0.9 | 23 | 0.1 |
| Hemorrhage | 28 | 5 | 30 | 4 |
| Hypertension | 11 | 5 | 14 | 7 |
| Second primary malignancy | 22‡ | 6 | 13 | 6 |
| Diarrhea | 18 | 0.9 | 19 | 2 |
| Nausea | 16 | 0 | 11 | 0.2 |
| Constipation | 15 | 0 | 13 | 0.3 |
| Abdominal pain | 12 | 2 | 10 | 0.6 |
| Cough | 18 | 0 | 19 | 0.1 |
| Dyspnea | 13 | 0 | 8 | 0.5 |
| Fatigue | 14 | 0.9 | 17 | 1 |
| Headache | 11 | 2 | 11 | 0.4 |
*Includes chronic lymphocytic leukemia, Waldenström’s macroglobulinemia, mantle cell lymphoma, follicular lymphoma, marginal zone lymphoma, hairy cell leukemia, diffuse large B-cell lymphoma, and Richter’s transformation.2
†Includes 1 fatal outcome.1
‡Includes non-melanoma skin cancer in 13%.1
Sequoia (Study 304): INCIDENCE OF LABORATORY ABNORMALITIES1
Select Lab Abnormalities (≥20%) That Worsened From Baseline in Cohorts 1 and 2
| Laboratory Abnormality | Cohort 1: Patients Without Del(17p) |
Cohort 2: Patients With Del(17p) |
||||
|---|---|---|---|---|---|---|
| BRUKINSA (n=239)* | BR (n=227) | BRUKINSA (N=111)† | ||||
| All Grades (%) | Grade ≥3 (%) | All Grades (%) | Grade ≥3 (%) | All Grades (%) | Grade ≥3 (%) | |
| Neutrophils decreased | 37 | 15 | 80 | 53 | 42 | 19‡ |
| Hemoglobin decreased | 29 | 3 | 66 | 8 | 26 | 4 |
| Platelets decreased | 27 | 2 | 61 | 11 | 23 | 0.9 |
| Leukocytes increased | 21§ | 21 | 0.4 | 0.4 | NR | NR |
| Glucose increased¶ | 55 | 7 | 67 | 10 | 52 | 6 |
| Creatinine increased | 22 | 0.8 | 18 | 0.4 | 27 | 0.9 |
| Magnesium increased | 22 | 0 | 14 | 0.4 | 31 | 0 |
| Alanine aminotransferase increased | 21 | 2 | 23 | 2 | NR | NR |
*In Cohort 1, the denominator used to calculate the rate varied from 239 to 227 based on the number of patients with a baseline value and at least 1 post-treatment value. Grading is based on NCI CTCAE criteria.
†In Cohort 2, the denominator used to calculate the rate varied from 110 to 111 based on the number of patients with a baseline value and at least 1 post-treatment value. Grading is based on NCI CTCAE criteria.
‡Grade 4, 9%.
§Lymphocytes increased in 15%.
¶Patients on study were not required to fast for lab tests.
SEQUOIA (STUDY 304): SELECT Adverse Events (AEs) OF SPECIAL INTEREST1-3
| Adverse Events | SEQUOIA | Pooled Safety Population* | ||||
|---|---|---|---|---|---|---|
| BRUKINSA (n=240) | BR (n=227) | BRUKINSA (N=1550) | ||||
| All Grades (%) | Grade ≥3 (%) | All Grades (%) | Grade ≥3 (%) | All Grades (%) | Grade ≥3 (%) | |
| Fatigue | 12 | 1 | 15 | 0.9 | 17 | 1 |
| Headache | 11 | 0 | 7 | 0 | 11 | 0.4 |
| Myalgia | 4 | 0 | 1 | 0 | 4 | 0.4 |
| Arthralgia | 13 | 0.8 | 9 | 0.4 | 14 | 0.7 |
| Atrial fibrillation/flutter† | 3 | 0.4 | 3 | 1 | 4 | 2 |
| Hypertension | 14 | 6 | 11 | 5 | 14 | 7 |
| Major bleeding‡ | 5 | 4 | 2 | 2 | 5 | 4 |
*Includes chronic lymphocytic leukemia, Waldenström’s macroglobulinemia, mantle cell lymphoma, follicular lymphoma, marginal zone lymphoma, hairy cell leukemia, diffuse large B-cell lymphoma, and Richter’s transformation.2
†Includes rates of atrial fibrillation only; does not include flutter.2
‡Major bleeding includes subdural hematoma or subdural hemorrhage.2
SEQUOIA (STUDY 304):
LOWER RATES OF DOSE REDUCTIONS AND DISCONTINUATION DUE TO AEs3
AE=adverse event; AR=adverse reaction; BR=bendamustine+rituximab; NCI CTCAE=National Cancer Institute Common Terminology Criteria for Adverse Events; NR=not reported.
Second line
ALPINE (STUDY 305): OVERALL INCIDENCE OF ADVERSE REACTIONS (ARs)1,2
| Adverse Reactions | ARs in ≥10% of Patients | Pooled Safety Population* | ||||
|---|---|---|---|---|---|---|
| BRUKINSA (n=324) | Ibrutinib (n=324) | BRUKINSA (N=1550) | ||||
| All Grades (%) | Grade ≥3 (%) | All Grades (%) | Grade ≥3 (%) | All Grades (%) | Grade ≥3 (%) | |
| Upper respiratory tract infection | 27 | 1 | 22 | 1 | 39 | 2 |
| Pneumonia | 18† | 9 | 19‡ | 11 | 20 | 11 |
| COVID-19 | 14† | 7 | 10‡ | 5 | 5 | 3 |
| Musculoskeletal pain | 26 | 0.6 | 28 | 0.6 | 30 | 2 |
| Hemorrhage | 24† | 3 | 26‡ | 4 | 30 | 4 |
| Hypertension | 19 | 13 | 20 | 13 | 14 | 7 |
| Rash | 20 | 1 | 21 | 0.9 | 28 | 0.9 |
| Bruising | 16 | 0 | 14 | 0 | 23 | 0.1 |
| Diarrhea | 14 | 2 | 22 | 0.9 | 19 | 2 |
| Fatigue | 13 | 0.9 | 14 | 0.9 | 17 | 1 |
| Cough | 11 | 0.3 | 11 | 0 | 19 | 0.1 |
| Dizziness | 10 | 0 | 7 | 0 | 11 | 0.3 |
Rates of hypertension were comparable between BRUKINSA and ibrutinib1
-
A medical history of hypertension was reported in more than half of these patient events for both BRUKINSA and ibrutinib2
*Includes chronic lymphocytic leukemia, Waldenström’s macroglobulinemia, mantle cell lymphoma, follicular lymphoma, marginal zone lymphoma, hairy cell leukemia, diffuse large B-cell lymphoma, and Richter’s transformation.2
†Includes fatal outcomes: pneumonia (9 patients), COVID-19 (8 patients), and hemorrhage (1 patient).1
‡Includes fatal outcomes: pneumonia (10 patients), COVID-19 (9 patients), and hemorrhage (2 patients).1
ALPINE (STUDY 305): INCIDENCE OF LAB ABNORMALITIES1
Select Lab Abnormalities (≥20%) That Worsened From Baseline
| Laboratory Abnormality | ||||
|---|---|---|---|---|
| BRUKINSA (n=321) | Ibrutinib (n=321)* | |||
| All Grades (%) | Grade ≥3 (%) | All Grades (%) | Grade ≥3 (%) | |
| Neutrophils decreased | 43 | 15 | 33 | 16 |
| Hemoglobin decreased | 28 | 4 | 32 | 4 |
| Lymphocytes increased | 24 | 19 | 26 | 19 |
| Platelets decreased | 22 | 4 | 24 | 3 |
| Glucose increased† | 52 | 5 | 29 | 3 |
| Creatinine increased | 26 | 0 | 23 | 0 |
| Phosphate decreased | 21 | 3 | 13 | 2 |
| Calcium decreased | 21 | 0.6 | 29 | 0 |
*The denominator used to calculate rates of lab abnormalities varied from 320 to 321 in the ibrutinib arm based on the number of patients with a baseline value and at least 1 post-treatment value. Grading is based on NCI CTCAE criteria.
†Patients on study were not required to fast for lab tests.
LOWER RATES OF CARDIAC DISORDERS, INCLUDING AFIB/FLUTTER,
AND NO CARDIAC DEATHS vs IBRUTINIB*4,5
*Assessed by both IRC and investigator with similar results. Median duration of treatment: 28.4 months for BRUKINSA and 24.3 months for ibrutinib.4
†Cardiac disorders is a grouped term that includes atrial fibrillation and atrial flutter.4
| BRUKINSA (n=324) |
Ibrutinib (n=324) |
|
|---|---|---|
| Cardiac adverse events | 69 (21.3%) | 96 (29.6%) |
| Serious cardiac adverse events | 6 (1.9%) | 25 (7.7%) |
| Cardiac adverse events leading to treatment discontinuation* | 1 (0.3%) | 14 (4.3%) |
| Fatal cardiac events | 0 (0%) | 6 (1.9%) |
*BRUKINSA cardiac-related discontinuation in 1 patient was for ventricular extrasystoles. Ibrutinib cardiac-related discontinuations were for atrial fibrillation (5), cardiac arrest (2), cardiac failure (2), cardiac failure acute (1), congestive cardiomyopathy (1), myocardial infarction (1), palpitations (1), and ventricular fibrillation (1).4
Assessed by both IRC and investigator with similar results. Median duration of treatment: 28.4 months for BRUKINSA and 24.3 months for ibrutinib.4
SELECT ADVERSE REACTIONS OF SPECIAL INTEREST
IN ALPINE (STUDY 305)1,2,4
| Adverse Reactions | ALPINE | Pooled Safety Population* | ||||
|---|---|---|---|---|---|---|
| BRUKINSA (n=324) | Ibrutinib (n=324) | BRUKINSA (N=1550) | ||||
| All Grades (%) | Grade ≥3 (%) | All Grades (%) | Grade ≥3 (%) | All Grades (%) | Grade ≥3 (%) | |
| Fatigue | 13 | 0.9 | 14 | 0.9 | 17 | 1 |
| Headache | 8 | 0 | 9 | 0 | 11 | 0.4 |
| Myalgia | 3 | 0 | 4 | 0 | 4 | 0.4 |
| Arthralgia | 14 | 0 | 15 | 0.3 | 14 | 0.7 |
| Atrial fibrillation and flutter | 5 | 3 | 13 | 4 | 4 | 2 |
| Hypertension | 19 | 13 | 20 | 13 | 14 | 7 |
| Major hemorrhage† | 4 | 3 | 4 | 4 | 5 | 4 |
*Includes chronic lymphocytic leukemia, Waldenström’s macroglobulinemia, mantle cell lymphoma, follicular lymphoma, marginal zone lymphoma, hairy cell leukemia, diffuse large B-cell lymphoma, and Richter’s transformation.2
†Hematuria was the most common major hemorrhage.2
ALPINE (STUDY 305): LOWer RATES OF DOSE REDUCTIONS AND DISCONTINUATION DUE TO ADVERSE EVENTS (AEs)4
*BRUKINSA cardiac-related discontinuation in 1 patient was for ventricular extrasystoles. Ibrutinib cardiac-related discontinuations were for atrial fibrillation (5), cardiac arrest (2), cardiac failure (2), cardiac failure acute (1), congestive cardiomyopathy (1), myocardial infarction (1), palpitations (1), and ventricular fibrillation (1).
AE=adverse event; afib=atrial fibrillation; AR=adverse reaction; IRC=independent review committee; NCI CTCAE=National Cancer Institute Common Terminology Criteria for Adverse Events.
Dr Anthony Nguyen discusses the safety profile of BRUKINSA vs ibrutinib in CLL
DISCOVER MORE VIDEOS
Long-term data*
Study 003:
A global supportive Phase 1/2, open-label, single-arm trial that included patients with treatment-naïve or relapsed/refractory CLL/SLL and evaluated ~4 years of safety and ~3 years of efficacy data6
ADVERSE EVENTS OF SPECIAL INTEREST
DECREASED OVER TIME6
Incidence of Treatment-Emergent Adverse Events (TEAEs)
Over Time (Grade ≥3)
-
Atrial fibrillation remained consistently low
-
No new safety signals
-
Low discontinuation rate of 10% over 4 years (N=123)
Overall median duration of treatment: 43 months.
Exploratory long-term analysis; all data are descriptive in nature.
Study 003 was a global supportive Phase 1/2 trial for 1L and 2L CLL.
*Assessed by IRC.
1L=first line; 2L=second line; CLL=chronic lymphocytic leukemia; IRC=independent review committee; SLL=small lymphocytic lymphoma.
