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A.R. Mato et al.
Treatment interruption
Of the 194 patients receiving VenR, 137 (70.6%) required a total of 316 interruptions to venetoclax treatment. Most patients interrupted treatment multiple times, with only 55 of 137 (40.1%) patients interrupting treatment just once. Of the other 82 of 137 patients, 37 (27.0%) interrupted treatment twice, 20 (14.6%) three times, 12 (8.8%) four times and 13 five or more times (n=6 for five interruptions [4.4%], n=2 for six interruptions [1.5%], n=3 for seven
Table 4. MURANO: adverse events leading to discontinuation, dose interrup- tion or dose reduction of venetoclax treatment.
interruptions [2.2%] and n=2 for eight interruptions [1.5%]). Reason for treatment interruption was not cap- tured specifically in the MURANO study, unless required for management of AE. Most of the interruptions (212 of 316) occurred during the combination treatment phase, with 117 of 194 patients (60.3%) interrupting treatment during combination therapy (212 interruptions) versus 62 of 194 patients (32.0%) with interruptions during the monotherapy treatment phase (104 interruptions).
The median consecutive days duration of treatment interruption was 9 days (range, 1–93). Of the 137 patients with treatment interruptions, 61 (44.5%) had interruptions lasting 1–7 consecutive days, 30 (21.9%) had interruptions lasting 8–14 consecutive days, 13 (9.5%) had interruptions lasting 15–21 consecutive days, 21 (15.3%) had interrup- tions lasting 22–28 consecutive days and 12 (8.8%) had interruptions lasting >28 consecutive days (based on the
Venetoclax treatment (n=194)
Discontinuation Interruption
Dose reduction
28 (14.4) 37
19 (9.8) 25 16 (8.2) 0
0
1 (0.5) 2 (1.0) 0
0 0 0 0 0 0
0 0 0 0 0 0
1 (0.5) 1
0
0
0
0
1 (0.5)
4 (2.1) 4
Number of patients with ≥1 AE, n (%) Total number of events, n
Blood and lymphatic system disorders, n (%)
Total number of patients with ≥1 AE Total number of events Neutropenia
Thrombocytopenia
Autoimmune hemolytic anemia* Anemia
Febrile neutropenia
Immune thrombocytopenic purpura
Neoplasms benign, malignant and unspecified,† n (%)
Total number of patients with ≥1 AE Total number of events
Colorectal cancer
Metastasis
Metastatic malignant melanoma Pancreatic carcinoma
General disorders and administration
32 (16.5) 41
14 (7.2) 16
6 (3.1) 5 (2.6) 2 (1.0) 1 (0.5) 1 (0.5) 1 (0.5)
5 (2.6) 5
2 (1.0) 1 (0.5) 1 (0.5) 1 (0.5)
4 (2.1) 4
1 (0.5) 1 (0.5) 1 (0.5) 1 (0.5)
4 (2.1) 5
2 (1.0) 1 (0.5) 1 (0.5) 1 (0.5) 0
3 (1.5) 3
1 (0.5) 1 (0.5) 1 (0.5) 0
0
2 (1.0) 2
1 (0.5) 1 (0.5) 0
134 (69.1) 344
95 (49.0) 180 84 (43.3) 9 (4.6) 2 (1.0) 3 (1.5) 3 (1.5) 0
1 (0.5) 1
0
0
1 (0.5) 0
8 (4.1) 8
1 (0.5) 3 (1.5) 0
0
47 (24.2) 70
8 (4.1) 1 (0.5) 1 (0.5) 0
8 (4.1)
16 (8.2) 29
continued from previous column
Respiratory, thoracic and mediastinal disorders, n (%)
Total number of patients with ≥1 AE Total number of events
Acute respiratory failure Hydrothorax
Ear and labyrinth disorders, n (%) Total number of patients with ≥1 AE Total number of events
Vertigo
Nervous system disorders, n (%)
Total number of patients with ≥1 AE Total number of events
Status epilepticus
Metabolism and nutrition disorders, n (%) Total number of patients with ≥1 AE Total number of events
Musculoskeletal and connective tissue disorders, n (%)
Total number of patients with ≥1 AE Total number of events
Skin and subcutaneous tissue disorders, n (%)
Total number of patients with ≥1 AE Total number of events
Cardiac disorders, n (%)
Total number of patients with ≥1 AE Total number of events
Hepatobiliary disorders, n (%)
Total number of patients with ≥1 AE Total number of events
Injury, poisoning and procedural complications, n (%)
Total number of patients with ≥1 AE Total number of events
Vascular disorders, n (%)
Total number of patients with ≥1 AE Total number of events
Reproductive system and breast disorders, n (%)
Total number of patients with ≥1 AE
Total number of events
2 (1.0) 2
1 (0.5) 1 (0.5)
1 (0.5) 1
1 (0.5)
1 (0.5) 1
1 (0.5)
0 0
0 0
0 0
0 0
0 0
0 0
0 0
0
0
2 (1.0) 2
0
0
0 0 0
2 (1.0) 2
0
10 (5.2) 11
3 (1.5) 4
3 (1.5) 3
2 (1.0) 2
2 (1.0) 2
2 (1.0) 2
2 (1.0) 2
1 (0.5) 1
0 0 0 0
0 0 0
0 0 0
1 (0.5) 2
0 0
1 (0.5) 1
0 0
1 (0.5) 1
0 0
0 0
0
0
site conditions, n (%)
Total number of patients with ≥1 Total number of events
Asthenia
Pyrexia
Sudden cardiac death*
Sudden death
Infections and infestations, n (%) Total number of patients with ≥1 Total number of events Pneumonia*
Appendicitis
Lung infection
Peritoneal tuberculosis
Upper respiratory tract infection
Gastrointestinal disorders, n (%) Total number of patients with ≥1 Total number of events
Ascites
Crohn’s disease
Diarrhea
Abdominal discomfort Small intestinal obstruction
AE
AE
AE
Investigations, n (%)
Total number of patients with ≥1
Total number of events
Alanine aminotransferase increased Neutrophil count decreased Aspartate aminotransferase increased
0
9 (4.6) 0
0
15 (7.7) 25
3 (1.5) 5 (2.6) 0
0
2 (1.0) 1 (0.5) 1 (0.5)
2 (1.0) 3
1 (0.5) 1 (0.5) 1 (0.5)
AE
00
*Includes event for patient whose primary reason for discontinuation was not due to an AE (primary reason for discontinuation for the patient with autoimmune hemolytic anemia was physician decision, for the patient with sudden cardiac death was death and for the patient with pneumonia was physician decision); †Including cysts and polyps. AE: adverse event.
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