Safety profile in the Phase 3 trial1
Reported adverse reactions were generally consistent with the known safety profile of cytarabine and daunorubicin therapy
Common adverse reactions (≥10% incidence in the VYXEOS arm) during the induction phase
- Fatal treatment-emergent CNS hemorrhage not in the setting of progressive disease occurred in 2% of patients in the VYXEOS arm and 0.7% of patients in the control arm1
| Adverse reaction | All gradesa | |
|---|---|---|
| VYXEOS
(n=153) n (%) |
7+3b
(n=151) n (%) |
|
| Hemorrhage | 107 (70) | 74 (49) |
| Febrile neutropenia | 104 (68) | 103 (68) |
| Rash | 82 (54) | 55 (36) |
| Edema | 78 (51) | 90 (60) |
| Nausea | 72 (47) | 79 (52) |
| Diarrhea/Colitis | 69 (45) | 100 (66) |
| Mucositis | 67 (44) | 69 (46) |
| Constipation | 61 (40) | 57 (38) |
| Musculoskeletal pain | 58 (38) | 52 (34) |
| Abdominal pain | 51 (33) | 45 (30) |
| Cough | 51 (33) | 34 (23) |
| Headache | 51 (33) | 36 (24) |
| Dyspnea | 49 (32) | 51 (34) |
| Fatigue | 49 (32) | 58 (38) |
| Arrhythmia | 46 (30) | 41 (27) |
| Decreased appetite | 44 (29) | 57 (38) |
| Pneumonia (excluding fungal) | 39 (26) | 35 (23) |
| Sleep disorders | 38 (25) | 42 (28) |
| Bacteremia (excluding sepsis) | 37 (24) | 37 (25) |
| Vomiting | 37 (24) | 33 (22) |
| Chills | 35 (23) | 38 (25) |
| Hypotension | 30 (20) | 32 (21) |
| Non-conduction cardiotoxicity | 31 (20) | 27 (18) |
| Dizziness | 27 (18) | 26 (17) |
| Fungal infection | 27 (18) | 19 (13) |
| Hypertension | 28 (18) | 22 (15) |
| Hypoxia | 28 (18) | 31 (21) |
| Upper respiratory infections (excluding fungal) | 28 (18) | 19 (13) |
| Chest pain | 26 (17) | 22 (15) |
| Pyrexia | 26 (17) | 23 (15) |
| Catheter/device/injection site reaction | 24 (16) | 15 (10) |
| Delirium | 24 (16) | 33 (22) |
| Pleural effusion | 24 (16) | 25 (17) |
| Anxiety | 21 (14) | 16 (11) |
| Pruritus | 23 (15) | 14 (9) |
| Sepsis (excluding fungal) | 17 (11) | 20 (13) |
| Hemorrhoids | 16 (11) | 12 (8) |
| Petechiae | 17 (11) | 17 (11) |
| Renal insufficiency | 17 (11) | 17 (11) |
| Transfusion reactions | 17 (11) | 16 (11) |
| Visual impairment (except bleeding) | 16 (11) | 8 (5) |
| Adverse reaction | Grades 3 to 5a | |
|---|---|---|
| VYXEOS
(n=153) n (%) |
7+3b
(n=151) n (%) |
|
| Hemorrhage | 15 (10) | 9 (6) |
| Febrile neutropenia | 101 (66) | 102 (68) |
| Rash | 8 (5) | 2 (1) |
| Edema | 2 (2) | 5 (3) |
| Nausea | 1 (1) | 1 (1) |
| Diarrhea/Colitis | 4 (3) | 10 (7) |
| Mucositis | 2 (1) | 7 (5) |
| Constipation | 0 | 0 |
| Musculoskeletal pain | 5 (3) | 4 (3) |
| Abdominal pain | 3 (2) | 3 (2) |
| Cough | 0 | 1 (1) |
| Headache | 2 (1) | 1 (1) |
| Dyspnea | 17 (11) | 15 (10) |
| Fatigue | 8 (5) | 8 (5) |
| Arrhythmia | 10 (7) | 7 (5) |
| Decreased appetite | 2 (1) | 5 (3) |
| Pneumonia (excluding fungal) | 30 (20) | 26 (17) |
| Sleep disorders | 2 (1) | 1 (1) |
| Bacteremia (excluding sepsis) | 35 (23) | 31 (21) |
| Vomiting | 0 | 0 |
| Chills | 0 | 0 |
| Hypotension | 7 (5) | 1 (1) |
| Non-conduction cardiotoxicity | 13 (9) | 15 (10) |
| Dizziness | 1 (1) | 0 |
| Fungal infection | 11 (7) | 9 (6) |
| Hypertension | 15 (10) | 8 (5) |
| Hypoxia | 19 (12) | 23 (15) |
| Upper respiratory infections (excluding fungal) | 4 (3) | 1 (1) |
| Chest pain | 5 (3) | 0 |
| Pyrexia | 1 (1) | 2 (1) |
| Catheter/device/injection site reaction | 0 | 0 |
| Delirium | 4 (3) | 9 (6) |
| Pleural effusion | 3 (2) | 2 (1) |
| Anxiety | 0 | 0 |
| Pruritus | 0 | 0 |
| Sepsis (excluding fungal) | N/A | N/A |
| Hemorrhoids | 0 | 0 |
| Petechiae | 0 | 0 |
| Renal insufficiency | 7 (5) | 7 (5) |
| Transfusion reactions | 3 (2) | 1 (1) |
| Visual impairment (except bleeding) | 0 | 0 |
- Adverse reactions were graded using National Cancer Institute Common Terminology Criteria for Adverse Events version 3.0.
- Cytarabine and daunorubicin.
Lower 30- and 60-day mortality rates vs 7+31,a
30- and 60-day overall all-cause mortality1
- 9 patients each in the VYXEOS arm (6%) and control arm (6%) had a fatal adverse reaction on treatment or within 30 days of therapy that was not in the setting of progressive disease1
- Fatal adverse reactions in the VYXEOS arm included infection, CNS hemorrhage, and respiratory failure1
- Cytarabine and daunorubicin.
Time to recovery of absolute neutrophil count and platelets may be prolonged with VYXEOS and require additional monitoring1
| Prolonged cytopenias for patients in Phase 3 trial1 | ||||
|---|---|---|---|---|
| Induction 1 | ||||
| VYXEOS
(n=58) n (%) |
7+3b
(n=34) n (%) |
|||
| Prolonged thrombocytopeniaa | 16 (28) | 4 (12) | ||
| Prolonged neutropeniaa | 10 (17) | 1 (3) | ||
| Prolonged cytopenias for patients in Phase 3 trial1 | ||||
|---|---|---|---|---|
| Consolidation 1c | ||||
| VYXEOS
(n=48) n (%) |
5+2b
(n=32) n (%) |
|||
| Prolonged thrombocytopeniaa | 12 (25) | 5 (16) | ||
| Prolonged neutropeniaa | 5 (10) | 1 (3) | ||
- Platelets <50 Gi/L or neutrophils <0.5 Gi/L lasting past cycle Day 42 in the absence of active leukemia.
- Cytarabine and daunorubicin.
- Patients receiving at least 1 consolidation.
