The Safety of Brukinsa
DEMONSTRATED SAFETY PROFILE IN R/R MCL
| Combined adverse reactions (ARs) in ≥10% of patients with MCL (N=118)1 | Pooled data: ARs in patients with hematologic malignancies (N=847)*1,2 | |||
|---|---|---|---|---|
| Adverse Reaction | All Grades (%) | Grade ≥3 (%) | All Grades (%) | Grade ≥3 (%) |
| Upper respiratory tract infection | 39 | 0 | 46.5 | 3.3 |
| Rash | 36 | 0 | 30.7 | 0.7 |
| Diarrhea | 23 | 0.8 | 23.5 | 1.9 |
| Pneumonia | 15 | 10 | 21.3 | 11.3 |
| Musculoskeletal pain | 14 | 3.4 | 29.8 | 2.8 |
| Bruising | 14 | 0 | 25.3 | 0.1 |
| Constipation | 13 | 0 | 16.2 | 0.4 |
| Hypertension | 12 | 3.4 | 11.7 | 5.2 |
| Cough | 12 | 0 | 22.9 | 0.1 |
| Hemorrhage | 11 | 3.4 | 35.4 | 3.4 |
| Urinary tract infection | 11 | 0.8 | 16.2 | 2.6 |
| Select Laboratory Abnormalities† (≥20%) in Patients With MCL in Studies BGB-3111-206 and BGB-3111-AU-0031 | ||
|---|---|---|
| Laboratory Parameter | Percent of Patients (N=118) | |
| All Grades (%) | Grade 3 or 4 (%) | |
| Hematologic abnormalities | ||
| Neutrophils decreased | 45 | 20 |
| Platelets decreased | 40 | 7 |
| Hemoglobin decreased | 27 | 6 |
| Lymphocytosis‡ | 41 | 16 |
| Chemistry abnormalities | ||
| Blood uric acid increased | 29 | 2.6 |
| ALT increased | 28 | 0.9 |
| Bilirubin increased | 24 | 0.9 |
No patients discontinued due to neutropenia and 2 patients had febrile neutropenia. Patients on study received growth factor support as needed.3
| ars of special interest in the pooled safety population (N=847)1,2 |
||
|---|---|---|
| Adverse Reaction | Percent of Patients (N=847) | |
| All Grades (%) | Grade ≥3 (%) | |
| Fatigue2 | 19.5 | 1.5 |
| Headache2 | 12.9 | 0.6 |
| Arthralgia2 | 10.7 | 0.9 |
| Myalgia2 | 4.6 | 0.6 |
| Atrial fibrillation and atrial flutter1 | 3.2 | 1.1 |
The most common ARs, including laboratory abnormalities (≥30%; pooled safety population N=847), included neutrophil count decreased (54%), upper respiratory tract infection (47%), platelet count decreased (41%), hemorrhage (35%), lymphocyte count decreased (31%), rash (31%), and musculoskeletal pain (30%).1
*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
†Based on laboratory measurements.
‡Asymptomatic lymphocytosis is a known effect of BTK inhibition.
Long-term safety analysis IN MCL
The overall safety profile was unchanged at 35 months.1,4
Most ARs occurred during the early stage of BRUKINSA treatment. There were no additional cases of:
- Atrial fibrillation
- Atrial flutter
- Grade ≥3 cardiac ARs
With 35.3 months of follow-up, the most common (≥20%) TEAEs observed were decreased neutrophil count (46.5%), upper respiratory tract infection (38.4%), rash (36.0%), decreased white blood cell count (33.7%), and decreased platelet count (32.6%); most were Grade 1/2 events.
The prevalence of neutropenia with any grade or Grade ≥3 decreased after the first year; no Grade ≥3 neutropenia occurred after 18 months.
No new TEAEs led to treatment discontinuation or dose reduction during the longer follow-up time.
Dose reduction and treatment
discontinuation rates IN MCL1
due to ARs1
due to ARs1
ALT=alanine aminotransferase; ARs=adverse reactions; BTK=Bruton's tyrosine kinase; MCL=mantle cell lymphoma; R/R=relapsed/refractory; TEAEs=treatment-emergent adverse events.
