ASH News Daily 2017 - Issue 2 - A-9

ASH NEWS DAILY

Sunday, December 10, 2017

Page A-9
®

HUMANITIES

Learning to Look
By nina Shah, Md, and
Peter ForSBerg, Md

ould looking at Monet's
Water Lilies give you more
insight into your 12 o'clock
new patient's anemia? Could
studying Edward Hopper's Automat alert you to the risk for complications following your patient's
upcoming stem cell transplant?
Sorry, just a second, I just need to
reply to this email, it'll only take

Summary of Clinical Trial Experience in
Diffuse Large B-Cell Lymphoma (DLBCL)
The data in Table 2 were obtained in the MabEASE
study, a comparative, randomized, parallel-group,
multicenter study to investigate the efficacy
of RITUXAN HYCELA (1,400 mg rituximab and
23,400 Units hyaluronidase human; n=369) versus
375 mg/m2 a rituximab product by intravenous
infusion (n=203) both in combination with CHOP
(R-CHOP) in previously untreated patients with
CD20-positive DLBCL.
Eighty two percent of patients receiving RITUXAN
HYCELA or rituximab completed all 8 cycles of
study treatment. In both RITUXAN HYCELA and
rituximab treatment groups, patients experienced
4.9 months median duration of rituximab exposure
in each arm.
The demographic characteristics were balanced
between the two treatment groups. Most patients
were Caucasian (79%) and more than half (54%)
were male. The study population had a median
age of 64 years (61% of patients aged ≥ 60 years)
with median BSA of 1.83 m2 (1.83 and 1.84 m2
for RITUXAN HYCELA and rituximab groups,
respectively).
The incidences of adverse reactions of any grade
(RITUXAN HYCELA [94%] vs. rituximab [92%])
(Table 2), Grade 3-4 adverse reactions (RITUXAN
HYCELA [63%] vs. rituximab [57%]), and serious
adverse reactions (RITUXAN HYCELA [42%]
vs. rituximab [37%]) were generally comparable
between the two treatment groups. The common
adverse reactions (occurring in ≥ 20% of patients
in any treatment group) were neutropenia, alopecia,
nausea, and anemia.
A total of 91 patients (16%) died, including 58/369
patients (16%) in RITUXAN HYCELA and 33/203
patients (16%) in rituximab. Of these patients, 44
patients (29 patients RITUXAN HYCELA [8%] vs.
15 patients rituximab [7%]) died due to adverse
reactions and 35 patients (22 patients RITUXAN
HYCELA [6%] vs. 13 patients rituximab [6%]) died
due to disease progression. Pneumonia (4 patients
RITUXAN HYCELA vs. 1 patient rituximab), septic
shock (2 patients RITUXAN HYCELA vs. 3 patients
rituximab), and cardiac arrest (1 patient RITUXAN
HYCELA vs. 3 patients rituximab) were the most
common adverse reactions leading to death.
The incidence of administration-related reactions
was balanced between the RITUXAN HYCELA
and rituximab groups (28% vs. 29%). Grade 1-2
ARRs constituted 97% of the overall ARRs for the
RITUXAN HYCELA arm and 80% for the rituximab
arm. Of the reported ARRs, local cutaneous
reactions with RITUXAN HYCELA were reported in
17 patients. These events resolved within a median
of 2 days from the onset (range 1 to 32 days).
Majority of these reactions were Grade 1 and 2
and were observed in 16 patients (4%).
Table 2: Incidence of Adverse Reactions in
≥ 5% of Patients with Previously Untreated
DLBCL Receiving RITUXAN HYCELA or
Rituximab in Combination with CHOP
Body System/
Adverse
Reactions

RITUXAN HYCELA
+ CHOP
(n=369)
All AEs
%

Grade 3-4
%

Gastrointestinal Disorders
Nausea
22
<1
Constipation
15
<1
Diarrhea
14
1
Vomiting
11
<1
Abdominal Pain 7
<1
Stomatitis
6
<1
Dyspepsia
5
0
General Disorders and
Administration Site Conditions
Fatigue
19
1
Pyrexia
13
<1
Asthenia
11
<1
Mucosal
Inflammation
8
<1
Edema Peripheral 8
<1
Infections
Pneumonia

Rituximab +
CHOP
(n=203)
All AEs
%

Grade 3-4
%

24
17
10
8
7
5
7

<1
<1
1
<1
<1
0
0

15
13
12

1
0
<1

8
4

1
0

Blood and Lymphatic System Disorders
Neutropenia
31
25
29
19
Anemia
23
5
21
4
Febrile
Neutropenia
14
14
12
11
Leukopenia
7
3
7
3
Lymphopenia
5
1
6
3

one ... Okay, I'm back, where was I?
Oh right, how much does the constant stream of distractions we deal
with compromise our focus?
These are just a few of the many
questions that will be raised by art
historian Amy E. Herman during
her special interest session "Blood
and Beyond: The Art of Perception," which will be presented this
afternoon at 4:30 p.m. in the Marcus
Auditorium in the Georgia World
Congress Center.

Table 2: Incidence of Adverse Reactions in
≥ 5% of Patients with Previously Untreated
DLBCL Receiving RITUXAN HYCELA or
Rituximab in Combination with CHOP (cont'd)
Body System/
Adverse
Reactions

RITUXAN HYCELA
+ CHOP
(n=369)
All AEs
%

Investigations
Neutrophil Count
Decreased
14
White Blood Cell
Count Decreased 7
Weight Decreased 8
Lymphocyte Count
Decreased
5

Grade 3-4
%

Rituximab +
CHOP
(n=203)
All AEs
%

Grade 3-4
%

4
<1

7
4

5
<1

Metabolism and Nutrition Disorders
Decreased Appetite 8
<1
9
Nervous System Disorders
Neuropathy
Peripheral
12
<1
Paresthesia
9
<1
Headache
6
0

12
6
7

<1
0
0
0

Skin and Subcutaneous Tissue Disorders
Alopecia
24
0
24
0
Respiratory, Thoracic and
Mediastinal Disorders
Cough
11
<1
Dyspnea
6
0

9
4

0
<1

Psychiatric Disorders
Insomnia
7

Summary of Clinical Trial Experience
in Chronic Lymphocytic Leukemia
The data in Table 3 were obtained in part 2 of
the SAWYER study, a two-part, comparative,
randomized, parallel-group, multicenter study
of RITUXAN HYCELA versus a rituximab product
by intravenous infusion both in combination
with fludarabine and cyclophosphamide (FC)
chemotherapy in patients with previously
untreated CLL.
The safety analysis population in part 2 of the
study included 85 patients receiving RITUXAN
HYCELA (1,600 mg rituximab/26,800 Units
hyaluronidase human) and 89 patients receiving
500 mg/m2 rituximab. In both RITUXAN HYCELA
and rituximab groups, patients had similar median
duration of rituximab exposure (4.9 vs. 4.7 months).
The majority of patients received all 6 cycles of
study treatment (86% RITUXAN HYCELA vs. 81%
rituximab).
The patient population was predominantly Caucasian
(96%), male (65%), with a median age of 60 years
and median BSA of 1.9 m2 (1.97 and 1.86 m2 for
the RITUXAN HYCELA and intravenous rituximab
groups, respectively). Overall, the treatment groups
were balanced with respect to demographic
characteristics, with the exception of more males in
the RITUXAN HYCELA arm (71% RITUXAN HYCELA
vs. 60% rituximab). Baseline disease characteristics
were similar between the two groups. Over half
of the patients (62%) had Binet Stage B disease
and the majority had typical CLL characterizations
(93%), with median time from first CLL diagnosis to
randomization being 18.5 months.
The incidences of adverse reactions were balanced
between the two treatment groups (96% RITUXAN
HYCELA vs. 91% rituximab), and the common
adverse reactions (occurring in ≥ 20% of patients
in any arm) were infections, neutropenia, nausea,
thrombocytopenia, pyrexia, anemia, vomiting, and
injection site erythema. The incidences of Grade 3-4
adverse reactions were also balanced between the
two treatment groups (69% RITUXAN HYCELA vs.
71% rituximab). The incidence of serious adverse
reactions was 29% for RITUXAN HYCELA and
33% for rituximab. The incidence of administrationrelated reactions was 44% for RITUXAN HYCELA
and 45% for rituximab). Of the reported ARRs, local
cutaneous reactions with RITUXAN HYCELA were
reported in 15 patients. These events resolved
within a median of 6 days from the onset (range 3 to
29 days). Majority of these reactions were Grade 1
and 2 and were observed in 14 patients (16%).
A total of 9 patients (5%) died, including 5 patients
in the RITUXAN HYCELA group and 4 patients
in the rituximab group. In the RITUXAN HYCELA
group, 1 patient died due to herpes zoster infection,
1 patient died as a result of progressive multifocal
leukoencephalopathy (PML) (considered by the
investigator as related to rituximab), and 3 patients
died due to disease progression. In the rituximab
group, 2 patients died due to diarrhea and listeriosis
and 2 patients died due to disease progression.

Ms. Herman, author of the book
Visual Intelligence, has been teaching doctors for more than a decade
how to improve their craft by carefully observing their patients. She
reports that as subspecialists we
run the risk of becoming "microfocused, at the cost of seeing the
big picture." Using a program she
developed during years spent as
the head of education at the Frick
Collection to educate medical trainees across New York City, Ms. Her-

Table 3: Incidence of Adverse Reactions in
≥ 5% of Patients with Previously Untreated
CLL Receiving RITUXAN HYCELA or Rituximab
in Combination with FC
Body System/
Adverse
Reactions

RITUXAN HYCELA
+ FC
(n=85)
All AEs
%

Grade 3-4
%

Gastrointestinal Disorders
Nausea
38
1
Vomiting
21
2
Diarrhea
12
0
Abdominal Pain
9
0
Constipation
8
0
General Disorders and
Administration Site Conditions
Pyrexia
32
5
Injection Site
Erythema
26
2
Injection Site Pain 16
1
Chills
13
0
Fatigue
11
0
Asthenia
8
1
Infections
Upper Respiratory
Tract Infection
Respiratory Tract
Infection
Bronchitis
Urinary Tract
Infection
Pneumonia

Rituximab
+ FC
(n=89)
All AEs
%

Grade 3-4
%

35
22
11
6
8

0
1
3
0
0

0
0
10
10
17

0
0
1
0
2

8
7

1
0

4
6

1
0

2
2

0
2

8
6

1
2

Blood and Lymphatic System Disorders
Neutropenia
65
56
58
Thrombocytopenia 24
6
26
Leukopenia
19
14
16
Anemia
13
5
24
Febrile Neutropenia 11
8
8

52
9
12
9
8

Musculoskeletal and
Connective Tissue Disorders
Arthralgia
9
0
Pain In Extremity
7
1
Bone Pain
6
0

1
2
2

0
0
0

Nervous System Disorders
Headache
7
0

Skin and Subcutaneous Tissue Disorders
Erythema
15
0
7
0
Rash
12
0
10
1
Pruritus
8
0
4
0
Respiratory, Thoracic and Mediastinal Disorders
Cough
13
0
11
0
Oropharyngeal Pain 6
0
3
0
Dyspnea
4
0
8
1
Psychiatric Disorders
Insomnia
1

Vascular Disorders
Hypotension
1
Hypertension
0

0
0

7
6

1
1

6.2 Immunogenicity
As with all therapeutic proteins, there is potential
for immunogenicity. The detection of antibody
formation is highly dependent on the sensitivity and
specificity of the assay. Additionally, the observed
incidence of antibody (including neutralizing
antibody) positivity in an assay may be influenced
by several factors including assay methodology,
sample handling, timing of sample collection,
concomitant medications, and underlying disease.
For these reasons, comparison of the incidence of
antibodies to RITUXAN HYCELA and rituximab in
the studies described below with the incidence of
antibodies in other studies or to other products may
be misleading.
In the SABRINA study, where previously untreated
patients with follicular lymphoma were treated with
RITUXAN HYCELA or rituximab in combination with
CVP or CHOP, the incidence of treatment-induced/
enhanced anti-rituximab antibodies in the RITUXAN
HYCELA group was similar to that observed in the
rituximab group (2.0% RITUXAN HYCELA vs. 1.5%
rituximab). The incidence of treatment-induced/
enhanced anti-recombinant human hyaluronidase
antibodies was 13% in the RITUXAN HYCELA
group compared with 8% in the rituximab group,
and the overall proportion of patients found to have
anti-recombinant human hyaluronidase antibodies

man helps teach physicians to look
beyond patients' charts to understand them more clearly. She has
also helped train professionals in
a variety of fields about how to become more effective at their work
through improved perception. This
includes teaching New York Police
Department officers about how to
separate facts from opinions when
investigating crimes, and Federal
»» BLOOD Page A-13

Table of Contents for the Digital Edition of ASH News Daily 2017 - Issue 2