ASH Clinical News Focus on Myeloid Malignancies | Page 8

BENDEKA ® (bendamustine hydrochloride) injection
Number (%) of patients
Bendamustine
Hydrochloride
Chlorambucil
(N=153)
(N=143)
System organ class
Preferred term
All Grades Grade 3/4 All Grades Grade 3/4
Respiratory, thoracic
and mediastinal
disorders
Cough
6 (4)
1 (<1)
7 (5)
1 (<1)
Skin and
subcutaneous
tissue disorders
Rash
12 (8)
4 (3)
7 (5)
3 (2)
Pruritus
8 (5)
0
2 (1)
0
The Grade 3 and 4 hematology laboratory test values by treatment group in
the randomized CLL clinical study are described in Table 2. These findings
confirm the myelosuppressive effects seen in patients treated with benda-
mustine hydrochloride. Red blood cell transfusions were administered to
20% of patients receiving bendamustine hydrochloride compared with 6%
of patients receiving chlorambucil.
Table 2: Incidence of Hematology Laboratory Abnormalities in Patients Who
Received bendamustine hydrochloride or Chlorambucil in the Randomized
CLL Clinical Study
Bendamustine
Hydrochloride
Chlorambucil
Laboratory
N=150
N=141
Abnormality
All Grades Grade 3/4 All Grades Grade 3/4
n (%)
n (%)
n (%)
n (%)
Hemoglobin Decreased
134 (89)
20 (13)
115 (82)
12 (9)
Platelets Decreased
116 (77)
16 (11)
110 (78)
14 (10)
Leukocytes Decreased
92 (61)
42 (28)
26 (18)
4 (3)
Lymphocytes Decreased
102 (68)
70 (47)
27 (19)
6 (4)
Neutrophils Decreased
113 (75)
65 (43)
86 (61)
30 (21)
In the randomized CLL trial, 34% of patients had bilirubin elevations,
some without associated significant elevations in AST and ALT. Grade 3
or 4 increased bilirubin occurred in 3% of patients. Increases in AST and
ALT of Grade 3 or 4 were limited to 1% and 3% of patients, respectively.
Patients treated with bendamustine hydrochloride may also have changes
in their creatinine levels. If abnormalities are detected, monitoring of these
parameters should be continued to ensure that significant deterioration does
not occur.
6.3
Clinical Trials Experience in NHL
The data described below reflect exposure to bendamustine hydrochloride
in 176 patients with indolent B-cell NHL treated in two single-arm studies.
The population was 31-84 years of age, 60% male, and 40% female. The
race distribution was 89% White, 7% Black, 3% Hispanic, 1% other, and
<1% Asian. These patients received bendamustine hydrochloride at a dose
of 120 mg/m 2 intravenously on Days 1 and 2 for up to eight 21-day cycles.
The adverse reactions occurring in at least 5% of the NHL patients,
regardless of severity, are shown in Table 3. The most common non-
hematologic adverse reactions (≥30%) were nausea (75%), fatigue (57%),
vomiting (40%), diarrhea (37%) and pyrexia (34%). The most common
non-hematologic Grade 3 or 4 adverse reactions (≥5%) were fatigue (11%),
febrile neutropenia (6%), and pneumonia, hypokalemia and dehydration,
each reported in 5% of patients.
Table 3: Non-Hematologic Adverse Reactions Occurring in at Least 5% of
NHL Patients Treated with bendamustine hydrochloride by System Organ
Class and Preferred Term (N=176)
System organ class
Number (%) of patients*
Preferred Term
All Grades
Grade 3/4
Total number of patients with
176 (100)
94 (53)
at least 1 adverse reaction
Cardiac Disorders
Tachycardia
13 (7)
0
Gastrointestinal disorders
Nausea
132 (75)
7 (4)
Vomiting
71 (40)
5 (3)
Diarrhea
65 (37)
6 (3)
BENDEKA ® (bendamustine hydrochloride) injection
System organ class
Number (%) of patients*
Preferred Term
All Grades
Grade 3/4
Gastrointestinal disorders continued
Constipation
51 (29)
1 (<1)
Stomatitis
27 (15)
1 (<1)
Abdominal pain
22 (13)
2 (1)
Dyspepsia
20 (11)
0
Gastroesophageal reflux disease
18 (10)
0
Dry mouth
15 (9)
1 (<1)
Abdominal pain upper
8 (5)
0
Abdominal distension
8 (5)
0
General disorders and administration site conditions
Fatigue
101 (57)
19 (11)
Pyrexia
59 (34)
3 (2)
Chills
24 (14)
0
Edema peripheral
23 (13)
1 (<1)
Asthenia
19 (11)
4 (2)
Chest pain
11 (6)
1 (<1)
Infusion site pain
11 (6)
0
Pain
10 (6)
0
Catheter site pain
8 (5)
0
Infections and infestations
Herpes zoster
18 (10)
5 (3)
Upper respiratory tract infection
18 (10)
0
Urinary tract infection
17 (10)
4 (2)
Sinusitis
15 (9)
0
Pneumonia
14 (8)
9 (5)
Febrile neutropenia
11 (6)
11 (6)
Oral candidiasis
11 (6)
2 (1)
Nasopharyngitis
11 (6)
0
Investigations
Weight decreased
31 (18)
3 (2)
Metabolism and nutrition disorders
Anorexia
40 (23)
3 (2)
Dehydration
24 (14)
8 (5)
Decreased appetite
22 (13)
1 (<1)
Hypokalemia
15 (9)
9 (5)
Musculoskeletal and connective tissue disorders
Back pain
25 (14)
5 (3)
Arthralgia
11 (6)
0
Pain in extremity
8 (5)
2 (1)
Bone pain
8 (5)
0
Nervous system disorders
Headache
36 (21)
0
Dizziness
25 (14)
0
Dysgeusia
13 (7)
Psychiatric disorder
Insomnia
23 (13)
Anxiety
14 (8)
Depression
10 (6)
Respiratory, thoracic and mediastinal disorders
Cough
38 (22)
Dyspnea
28 (16)
Pharyngolaryngeal pain
14 (8)
Wheezing
8 (5)
Nasal congestion
8 (5)
0
0
1 (<1)
0
1 (<1)
3 (2)
1 (<1)
0
0
continued