Table 4 : All Adverse Reactions in ≥5.0 % and Grade 3 / 4 Adverse Reactions | |||||||||||||
in ≥ 1.0 % of Patients in the Rd Continuous or Rd18 Arms * | |||||||||||||
Grade 3 / 4 Adverse | |||||||||||||
All Adverse Reactions a |
Reactions b |
||||||||||||
Rd |
Rd |
||||||||||||
System organ class Continuous |
Rd18 |
MPT |
Continuous |
Rd18 |
MPT |
||||||||
Preferred term |
( N = 532 ) |
( N = 540 ) |
( N = 541 ) |
( N = 532 ) |
( N = 540 ) |
( N = 541 ) |
|||||||
Musculoskeletal and connective tissue disorders | |||||||||||||
Back pain c |
170 ( 32 ) 145 ( 26.9 ) 116 ( 21.4 ) |
37 ( 7 ) |
34 ( 6.3 ) |
28 ( 5.2 ) |
|||||||||
Muscle spasms f |
109 ( 20.5 ) 102 ( 18.9 ) 61 ( 11.3 ) |
< 1 % |
< 1 % |
< 1 % |
|||||||||
Arthralgia f |
101 ( 19.0 ) 71 ( 13.1 ) |
66 ( 12.2 ) |
9 ( 1.7 ) |
8 ( 1.5 ) |
8 ( 1.5 ) |
||||||||
Bone pain f |
87 ( 16.4 ) |
77 ( 14.3 ) |
62 ( 11.5 ) |
16 ( 3.0 ) |
15 ( 2.8 ) |
14 ( 2.6 ) |
|||||||
Pain in extremity f |
79 ( 14.8 ) |
66 ( 12.2 ) |
61 ( 11.3 ) |
8 ( 1.5 ) |
8 ( 1.5 ) |
7 ( 1.3 ) |
|||||||
Musculoskeletal pain f |
67 ( 12.6 ) |
59 ( 10.9 ) |
36 ( 6.7 ) |
< 1 % |
< 1 % |
< 1 % |
|||||||
Musculoskeletal chest pain f |
60 ( 11.3 ) |
51 ( 9.4 ) |
39 ( 7.2 ) |
6 ( 1.1 ) |
< 1 % |
< 1 % |
|||||||
Muscular weakness f |
43 ( 8.1 ) |
35 ( 6.5 ) |
29 ( 5.4 ) |
< 1 % |
8 ( 1.5 ) |
< 1 % |
|||||||
Neck pain f |
40 ( 7.5 ) |
19 ( 3.5 ) |
10 ( 1.8 ) |
< 1 % |
< 1 % |
< 1 % |
|||||||
Infections and infestations | |||||||||||||
Bronchitis c |
90 ( 16.9 ) |
59 ( 10.9 ) |
43 ( 7.9 ) |
9 ( 1.7 ) |
6 ( 1.1 ) |
3 ( 0.6 ) |
|||||||
Nasopharyngitis f |
80 ( 15 ) |
54 ( 10 ) |
33 ( 6.1 ) |
0 ( 0.0 ) |
0 ( 0.0 ) |
0 ( 0.0 ) |
|||||||
Urinary tract infection f |
76 ( 14.3 ) |
63 ( 11.7 ) |
41 ( 7.6 ) |
8 ( 1.5 ) |
8 ( 1.5 ) |
< 1 % |
|||||||
Upper respiratory tract infection c % f |
69 ( 13.0 ) |
53 ( 9.8 ) |
31 ( 5.7 ) |
< 1 % |
8 ( 1.5 ) |
< 1 % |
|||||||
Pneumonia c @ |
93 ( 17.5 ) |
87 ( 16.1 ) |
56 ( 10.4 ) 60 ( 11.3 ) |
57 ( 10.5 ) |
41 ( 7.6 ) |
||||||||
Respiratory tract |
|||||||||||||
infection % |
35 ( 6.6 ) |
25 ( 4.6 ) |
21 ( 3.9 ) |
7 ( 1.3 ) |
4 ( 0.7 ) |
1 ( 0.2 ) |
|||||||
Influenza f |
33 ( 6.2 ) |
23 ( 4.3 ) |
15 ( 2.8 ) |
< 1 % |
< 1 % |
0 ( 0.0 ) |
|||||||
Gastroenteritis f |
32 ( 6.0 ) |
17 ( 3.1 ) |
13 ( 2.4 ) |
0 ( 0.0 ) |
< 1 % |
< 1 % |
|||||||
Lower respiratory tract infection |
29 ( 5.5 ) |
14 ( 2.6 ) |
16 ( 3.0 ) |
10 ( 1.9 ) |
3 ( 0.6 ) |
3 ( 0.6 ) |
|||||||
Rhinitis f |
29 ( 5.5 ) |
24 ( 4.4 ) |
14 ( 2.6 ) |
0 ( 0.0 ) |
0 ( 0.0 ) |
0 ( 0.0 ) |
|||||||
Cellulitis c |
< 5 % |
< 5 % |
< 5 % |
8 ( 1.5 ) |
3 ( 0.6 ) |
2 ( 0.4 ) |
|||||||
Sepsis c @ |
33 ( 6.2 ) |
26- ( 4.8 ) |
18 ( 3.3 ) |
26 ( 4.9 ) |
20 ( 3.7 ) |
13 ( 2.4 ) |
|||||||
Nervous system disorders | |||||||||||||
Headache f |
75 ( 14.1 ) |
52 ( 9.6 ) |
56 ( 10.4 ) |
< 1 % |
< 1 % |
< 1 % |
|||||||
Dysgeusia f |
39 ( 7.3 ) |
45 ( 8.3 ) |
22 ( 4.1 ) |
< 1 % |
0 ( 0.0 ) |
< 1 % |
|||||||
Blood and lymphatic system disorders d | |||||||||||||
Anemia |
233 ( 43.8 ) 193 ( 35.7 ) 229 ( 42.3 ) 97 ( 18.2 ) |
85 ( 15.7 ) 102 ( 18.9 ) |
|||||||||||
Neutropenia |
186 ( 35.0 ) 178 ( 33 ) 328 ( 60.6 ) 148 ( 27.8 ) 143 ( 26.5 ) 243 ( 44.9 ) |
||||||||||||
Thrombocytopenia |
104 ( 19.5 ) 100 ( 18.5 ) 135 ( 25.0 ) 44 ( 8.3 ) |
43 ( 8.0 ) |
60 ( 11.1 ) |
||||||||||
Febrile neutropenia |
7 ( 1.3 ) |
17 ( 3.1 ) |
15 ( 2.8 ) |
6 ( 1.1 ) |
16 ( 3.0 ) |
14 ( 2.6 ) |
|||||||
Pancytopenia |
5 ( 0.9 ) |
6 ( 1.1 ) |
7 ( 1.3 ) |
1 ( 0.2 ) |
3 ( 0.6 ) |
5 ( 0.9 ) |
|||||||
Respiratory , thoracic and mediastinal disorders | |||||||||||||
Cough f |
121 ( 22.7 ) 94 ( 17.4 ) |
68 ( 12.6 ) |
< 1 % |
< 1 % |
< 1 % |
||||||||
Dyspnea c , e |
117 ( 22.0 ) 89 ( 16.5 ) 113 ( 20.9 ) 30 ( 5.6 ) |
22 ( 4.1 ) |
18 ( 3.3 ) |
||||||||||
Epistaxis f |
32 ( 6.0 ) |
31 ( 5.7 ) |
17 ( 3.1 ) |
< 1 % |
< 1 % |
0 ( 0.0 ) |
|||||||
Oropharyngeal pain f |
30 ( 5.6 ) |
22 ( 4.1 ) |
14 ( 2.6 ) |
0 ( 0.0 ) |
0 ( 0.0 ) |
0 ( 0.0 ) |
|||||||
Dyspnea exertional e |
27 ( 5.1 ) |
29 ( 5.4 ) |
< 5 % |
6 ( 1.1 ) |
2 ( 0.4 ) |
0 ( 0.0 ) |
|||||||
Metabolism and nutrition disorders | |||||||||||||
Decreased | |||||||||||||
appetite |
123 ( 23.1 ) 115 ( 21.3 ) 72 ( 13.3 ) |
14 ( 2.6 ) |
7 ( 1.3 ) |
5 ( 0.9 ) |
|||||||||
Hypokalemia % |
91 ( 17.1 ) 62 ( 11.5 ) |
38 ( 7 ) |
35 ( 6.6 ) |
20 ( 3.7 ) |
11 ( 2.0 ) |
||||||||
Hyperglycemia |
62 ( 11.7 ) |
52 ( 9.6 ) |
19 ( 3.5 ) |
28 ( 5.3 ) |
23 ( 4.3 ) |
9 ( 1.7 ) |
|||||||
Hypocalcemia |
57 ( 10.7 ) |
56 ( 10.4 ) |
31 ( 5.7 ) |
23 ( 4.3 ) |
19 ( 3.5 ) |
8 ( 1.5 ) |
|||||||
Dehydration % |
25 ( 4.7 ) |
29 ( 5.4 ) |
17 ( 3.1 ) |
8 ( 1.5 ) |
13 ( 2.4 ) |
9 ( 1.7 ) |
|||||||
Gout e |
< 5 % |
< 5 % |
< 5 % |
8 ( 1.5 ) |
0 ( 0.0 ) |
0 ( 0.0 ) |
|||||||
Diabetes mellitus % e |
< 5 % |
< 5 % |
< 5 % |
8 ( 1.5 ) |
4 ( 0.7 ) |
2 ( 0.4 ) |
|||||||
Hypophosphatemia e |
< 5 % |
< 5 % |
< 5 % |
7 ( 1.3 ) |
3 ( 0.6 ) |
1 ( 0.2 ) |
|||||||
Hyponatremia % e |
< 5 % |
< 5 % |
< 5 % |
7 ( 1.3 ) |
13 ( 2.4 ) |
6 ( 1.1 ) |
|||||||
Skin and subcutaneous tissue disorders | |||||||||||||
Rash |
139 ( 26.1 ) 151 ( 28.0 ) 105 ( 19.4 ) 39 ( 7.3 ) |
38 ( 7.0 ) |
33 ( 6.1 ) |
||||||||||
Pruritus f |
47 ( 8.8 ) |
49 ( 9.1 ) |
24 ( 4.4 ) |
< 1 % |
< 1 % |
< 1 % ( continued ) |
Table 4 : All Adverse Reactions in ≥5.0 % and Grade 3 / 4 Adverse Reactions | |||||||||||
in ≥ 1.0 % of Patients in the Rd Continuous or Rd18 Arms * | |||||||||||
Grade 3 / 4 Adverse | |||||||||||
All Adverse Reactions a |
Reactions b |
||||||||||
Rd |
Rd |
||||||||||
System organ class Continuous |
Rd18 |
MPT |
Continuous |
Rd18 |
MPT |
||||||
Preferred term |
( N = 532 ) |
( N = 540 ) |
( N = 541 ) |
( N = 532 ) |
( N = 540 ) |
( N = 541 ) |
|||||
Psychiatric disorders | |||||||||||
Insomnia |
147 ( 27.6 ) 127 ( 23.5 ) |
53 ( 9.8 ) |
4 ( 0.8 ) |
6 ( 1.1 ) |
0 ( 0.0 ) |
||||||
Depression |
58 ( 10.9 ) |
46 ( 8.5 ) |
30 ( 5.5 ) |
10 ( 1.9 ) |
4 ( 0.7 ) |
1 ( 0.2 ) |
|||||
Vascular disorders Deep vein thrombosis c % |
55 ( 10.3 ) |
39 ( 7.2 ) |
22 ( 4.1 ) |
30 ( 5.6 ) |
20 ( 3.7 ) |
15 ( 2.8 ) |
|||||
Hypotension c % |
51 ( 9.6 ) |
35 ( 6.5 ) |
36 ( 6.7 ) |
11 ( 2.1 ) |
8 ( 1.5 ) |
6 ( 1.1 ) |
|||||
Injury , Poisoning , and Procedural Complications | |||||||||||
Fall f |
43 ( 8.1 ) |
25 ( 4.6 ) |
25 ( 4.6 ) |
< 1 % |
6 ( 1.1 ) |
6 ( 1.1 ) |
|||||
Contusion f |
33 ( 6.2 ) |
24 ( 4.4 ) |
15 ( 2.8 ) |
< 1 % |
< 1 % |
0 ( 0.0 ) |
|||||
Eye disorders Cataract |
73 ( 13.7 ) |
31 ( 5.7 ) |
5 ( 0.9 ) |
31 ( 5.8 ) |
14 ( 2.6 ) |
3 ( 0.6 ) |
|||||
Cataract subcapsular e |
< 5 % |
< 5 % |
< 5 % |
7 ( 1.3 ) |
0 ( 0.0 ) |
0 ( 0.0 ) |
|||||
Investigations Weight decreased |
72 ( 13.5 ) |
78 ( 14.4 ) |
48 ( 8.9 ) |
11 ( 2.1 ) |
4 ( 0.7 ) |
4 ( 0.7 ) |
|||||
Cardiac disorders Atrial fibrillation c |
37 ( 7.0 ) |
25 ( 4.6 ) |
25 ( 4.6 ) |
13 ( 2.4 ) |
9 ( 1.7 ) |
6 ( 1.1 ) |
|||||
Myocardial infarction ( including acute ) c , e |
< 5 % |
< 5 % |
< 5 % |
10 ( 1.9 ) |
3 ( 0.6 ) |
5 ( 0.9 ) |
|||||
Renal and Urinary disorders
Renal failure ( including acute ) c @, f
|
49 ( 9.2 ) |
54 ( 10.0 ) |
37 ( 6.8 ) |
28 ( 5.3 ) |
33 ( 6.1 ) |
29 ( 5.4 ) |
|||||
Neoplasms benign , malignant and unspecified ( Incl cysts and polyps ) | |||||||||||
Squamous cell | |||||||||||
carcinoma ce |
< 5 % |
< 5 % |
< 5 % |
8 ( 1.5 ) |
4 ( 0.7 ) |
0 ( 0.0 ) |
|||||
Basal cell carcinoma c e , f |
< 5 % |
< 5 % |
< 5 % |
< 1 % |
< 1 % |
0 ( 0.0 ) |
|||||
Note : System organ classes ( SOC ) and preferred terms ( PTs ) reflect coding of adverse | |||||||||||
reactions using MedDRA . A subject with multiple occurrences of an adverse | |||||||||||
reaction is counted only once under the applicable SOC / PT . | |||||||||||
a All treatment-emergent adverse reactions in at least 5.0 % of subjects in the | |||||||||||
Rd Continuous or Rd18 Arms and at least a 2.0 % higher frequency (%) in either the | |||||||||||
Rd Continuous or Rd18 Arms compared to the MPT Arm . | |||||||||||
b All grade 3 or 4 treatment-emergent adverse reactions in at least 1.0 % of subjects in | |||||||||||
the Rd Continuous or Rd18 Arms and at least a 1.0 % higher frequency (%) in either | |||||||||||
the Rd Continuous or Rd18 Arms compared to the MPT Arm . | |||||||||||
c
Serious treatment-emergent adverse reactions in at least 1.0 % of subjects in the
| |||||||||||
Rd Continuous or Rd18 Arms and at least a 1.0 % higher frequency (%) in either the | |||||||||||
Rd Continuous or Rd18 Arms compared to the MPT Arm . | |||||||||||
d Preferred terms for the blood and lymphatic system disorders SOC were included by | |||||||||||
medical judgment as known adverse reactions for Rd Continuous / Rd18 , and have also | |||||||||||
been reported as serious . | |||||||||||
e Footnote “ a ” not applicable | |||||||||||
f
Footnote “ b ” not applicable .
| |||||||||||
@ - adverse reactions in which at least one resulted in a fatal outcome | |||||||||||
%
- adverse reactions in which at least one was considered to be life threatening ( if the
| |||||||||||
outcome of the reaction was death , it is included with death cases ) | |||||||||||
* PTs for combined adverse reaction terms : | |||||||||||
Abdominal Pain : Abdominal pain , abdominal pain upper , abdominal pain lower , | |||||||||||
gastrointestinal pain | |||||||||||
Pneumonias : Pneumonia , lobar pneumonia , pneumonia pneumococcal , | |||||||||||
bronchopneumonia , pneumocystis jiroveci pneumonia , pneumonia legionella , pneumonia | |||||||||||
staphylococcal , pneumonia klebsiella , atypical pneumonia , pneumonia bacterial , | |||||||||||
pneumonia escherichia , pneumonia streptococcal , pneumonia viral | |||||||||||
Sepsis : Sepsis , septic shock , urosepsis , escherichia sepsis , neutropenic sepsis , | |||||||||||
pneumococcal sepsis , staphylococcal sepsis , bacterial sepsis , meningococcal sepsis , | |||||||||||
enterococcal sepsis , klebsiella sepsis , pseudomonal sepsis | |||||||||||
Rash : Rash , rash pruritic , rash erythematous , rash maculo-papular , rash generalised , | |||||||||||
rash papular , exfoliative rash , rash follicular , rash macular , drug rash with eosinophilia | |||||||||||
and systemic symptoms , erythema multiforme , rash pustular | |||||||||||
Deep Vein Thrombosis : Deep vein thrombosis , venous thrombosis limb , venous | |||||||||||
thrombosis |