ASH News Daily 2016 - Issue 1 - A-9


ASH News Daily

Saturday, December 3, 2016

Page A-9
®

Ham-Wasserman

tion of recurrent placenta-mediated
pregnancy complications. "This new
data highlights how important it is
not to prescribe medication merely
on the basis of belief or theory; what
we need is high-level evidence. I
think the ALIFE2 study will give
the final answer as to whether it is
worthwhile to test for thrombophilia
in this situation."
According to Dr. Middeldorp,
"Being a successful clinician and
researcher takes more than being
smart or being able to write or being
able to analyze data. It's how you tell
your story."

«« From Page A-8

prescribe LMWH. The reasoning behind this is becoming stronger and
stronger with every meta-analysis,
and now with data from AFFIRM."
The AFFIRM study is an individual
patient level meta-analysis that evaluates the role of LMWH to prevent
placenta-mediated pregnancy complications such as pre-eclampsia,
placental abruption, birth of a smallfor-gestational-age neonate, or late
fetal loss. Investigators from eight
trials, including Dr. Middeldorp,
pooled their individual patient data
and showed that there was no additional benefit of LMWH in preven-

GAZYVA +
Chlorambucil
n = 336
All
Grades %

Grades
3-4 %

Rituximab +
Chlorambucil
n = 321
All
Grades
Grades % 3-4 %

Injury, poisoning and procedural complications

Infusion
reactions

66

20

38

4

Blood and lymphatic system disordersa

Neutropenia
38
Thrombocytopenia 14
Leukopenia
6

33
10
4

32
7
2

28
3
<1

General disorders and administration site
conditions

Pyrexia

9

<1

7

<1

8
5

<1
0

Gastrointestinal disorders

Diarrhea
Constipation

10
8

2
0

Infections and infestations

Nasopharyngitis
Urinary tract
infection
a

6
5

<1
1

3
2

0
<1

Adverse reactions reported under "Blood and lymphatic system
disorders" reflect those reported by investigator as clinically
significant.

Table 5 Post-Baseline Laboratory
Abnormalities by CTCAE Grade in ≥ 5% of
Patients with CLL and at Least 2% Greater in
the GAZYVA Treated Arm (Stage 2)
Laboratory
Abnormalities

GAZYVA
+ Chlorambucil
n = 336
All
Grades
Grades %
3-4 %

Rituximab +
Chlorambucil
n = 321
All
Grades
Grades % 3-4 %

Hematology

Neutropenia
Lymphopenia
Leukopenia
Thrombocytopenia
Anemia

76
80
84
48
39

46
39
35
13
10

69
50
62
40
37

41
16
16
8
10

37
14
26
27

3
1
7
2

32
10
18
21

<1
<1
2
<1

28

2

21

1

23

<1

16

<1

Chemistry

Hypocalcemia
Hypokalemia
Hyponatremia
AST/SGOT
increased
ALT/SGPT
increased
Hypoalbuminemia

Speaker Change:
For the Scientific Committee on Bone Marrow Failure session titled
"Ribosomes and Ribosomopathies," speaker Dr. Maria Barna was
scheduled to present both today at 9:30 a.m. and tomorrow at 7:30
a.m. She will now be speaking only during today's session.
Speaker Change:
For the Education Program session titled "Common Consults in
Thrombosis," taking place today at 4 p.m., speaker Dr. Christine
Ribic is unable to attend, and has arranged for Dr. Wendy Lim to give
her talk instead.
Speaker Change:
For the Scientific Program session titled "Emerging Biology Leading to New Therapies in Follicular Lymphoma" taking place today at
4 p.m., speaker Dr. Nadel Bertrand is unable to present and will be
replaced by Dr. Laura Pasqualuci.

Dr. Skeith has no relevant conflicts of
interest.

Table 4 Summary of Adverse Reactions
Reported in ≥ 5% of Patients with CLL and at
Least 2% Greater in the GAZYVA Treated Arm
(Stage 2)
Adverse
Reactions
System Organ
Class

Saturday Schedule Changes

Summary of Clinical Trial Experience in
Non-Hodgkin Lymphoma
The safety of GAZYVA was evaluated based on
a safety population of 392 patients with indolent
NHL, of whom 81% had FL. In the population of
patients with FL, the profile of adverse reactions
was consistent with the overall indolent NHL
population. Patients were treated with either GAZYVA
in combination with bendamustine, followed by
GAZYVA monotherapy in patients that have not
progressed, or with bendamustine alone.
Patients randomized to the GAZYVA + bendamustine
arm received three weekly 1000 mg doses of GAZYVA
in the first cycle and a single dose of 1000 mg once
every 28 days for 5 additional cycles in combination
with bendamustine 90 mg/m2 on Days 1 and 2 in all
6 cycles. Patient randomized to the bendamustine
alone arm received 120 mg/m2 on Days 1 and 2.
This regimen continued for 6 cycles of 28 days
in duration. For patients who did not progress on
GAZYVA in combination with bendamustine, a
single dose of 1000 mg GAZYVA monotherapy was
given every two months until progression or for a
maximum of two years. During combination therapy
with GAZYVA and bendamustine, 79% of patients
received all 6 treatment cycles of GAZYVA and 76%
received all 6 treatment cycles of bendamustine
compared to 67% of patients in the bendamustine
alone arm.

The most common adverse reactions (incidence
≥ 10%) observed in patients with iNHL in the
GAZYVA containing arm were infusion reactions,
neutropenia, nausea, fatigue, cough, diarrhea,
constipation, pyrexia, thrombocytopenia, vomiting,
upper respiratory tract infection, decreased appetite,
arthralgia, sinusitis, anemia, asthenia and urinary
tract infection.
The most common Grade 3-4 adverse reactions
(incidence ≥ 10%) observed in patients with iNHL
in the GAZYVA containing arm were neutropenia,
thrombocytopenia and infusion reactions.
Table 6 Summary of Adverse Reactions
Reported in ≥5% of Patients with Indolent
NHL and at Least 2% Greater in the GAZYVA
plus Bendamustine Followed by GAZYVA
Monotherapy Treated Arm
Adverse
Reactions
System Organ
Class

GAZYVA
+ Bendamustine
Bendamustine
followed by
n = 198
GAZYVA monotherapy
n = 194
All
Grades
All
Grades
Grades %
3-4 % Grades % 3-4 %

Injury, Poisoning and Procedural Complications

Infusion related
reactionsa

69

11

63

6

Blood and Lymphatic System Disorders

Neutropenia
35
33
28
26
Gastrointestinal Disorders
Constipation
19
0
16
0
Dyspepsia
5
0
3
0
General Disorders and Administration Site
Conditions
Pyrexia
18
1
14
0
Asthenia
11
1
8
0
Infections and Infestations
Upper Respiratory 13
2
8
1
Tract Infection
Sinusitis
12
1
5
0
Urinary Tract
10
3
6
0
Infection
Nasopharyngitis
9
0
4
0
Musculoskeletal and Connective Tissue
Disorders

Arthralgia
12
0
5
0
Pain in Extremity
9
1
4
0
Respiratory, Thoracic and Mediastinal
Disorders
Cough
26
0
17
0
Nasal Congestion 7
0
2
0
Skin and Subcutaneous Tissue Disorders
Pruritus
9
0
6
0
a

Defined as any related adverse reaction that occurred during or
within 24 hours of infusion.

During the monotherapy period with GAZYVA, the
most common adverse reactions in patients with
iNHL were cough (15%), upper respiratory tract
infections (12%), neutropenia (11%), sinusitis
(10%), diarrhea (8%), infusion related reactions
(8%), nausea (8%), fatigue (8%), bronchitis (7%),
arthralgia (7%), pyrexia (6%), nasopharyngitis (6%),
and urinary tract infections (6%). The most common
Grade 3-4 adverse reactions during the monotherapy
period were neutropenia (10%), and anemia, febrile
neutropenia, thrombocytopenia, sepsis, upper
respiratory tract infection, and urinary tract infection
(all at 1%).

Table 7 Post-Baseline Laboratory
Abnormalities by CTCAE Grade in ≥ 5% of
Patients with iNHL and at Least 2% Greater
in the GAZYVA plus Bendamustine Followed
by GAZYVA Monotherapy Treated Arma
Laboratory
Abnormalities

GAZYVA
+ Bendamustine
Bendamustine
followed by GAZYVA
n = 198
monotherapy
n = 194
Grades
All
Grades
All
Grades %
3-4 % Grades % 3-4 %

Hematology

Neutropenia
Leukopenia
Lymphopenia
Chemistry

Hypocalcemia
Hypophosphatemia
ALT/SGPT
increased
Elevated creatinine
Creatinine Clearance
(decreased)
a

75
86
99

52
47
93

77
88
99

42
34
85

38
41
35

2
7
1

26
38
31

2
7
4

87
58

4
6

92
61

2
4

Two percent different in either the All Grades or Grade 3-4 Lab
Abnormalities.

In the monotherapy phase of treatment with
GAZYVA, the most frequently reported hematological
laboratory abnormalities were lymphopenia (80%),
leukopenia (63%), low hemoglobin (50%) and
neutropenia (46%). The most frequently reported
hematological Grade 3-4 laboratory abnormalities
during the monotherapy period were lymphopenia
(52%), neutropenia (27%) and leukopenia (20%).
In the monotherapy phase of treatment with
GAZYVA, the most frequently reported chemistry
laboratory abnormalities were elevated creatinine
(69%), decreased creatinine clearance (43%),
hypophosphatemia (25%), AST/SGOT increased
(24%) and ALT/SGPT increased (21%). The most
frequently reported chemistry Grade 3-4 laboratory
abnormalities during the monotherapy period were
hypophosphatemia (5%) and hyponatremia (3%).
Infusion Reactions:
Chronic Lymphocytic Leukemia
The incidence of infusion reactions was 65% with
the first infusion of GAZYVA. The incidence of
Grade 3 or 4 infusion reactions was 20% with 7%
of patients discontinuing therapy. The incidence of
reactions with subsequent infusions was 3% with the
second 1000 mg and < 1% thereafter. No Grade 3
or 4 infusion reactions were reported beyond the first
1000 mg infused.
Of the first 53 patients receiving GAZYVA on the
trial, 47 (89%) experienced an infusion reaction. After
this experience, study protocol modifications were
made to require premedication with a corticosteroid,
antihistamine, and acetaminophen. The first dose
was also divided into two infusions (100 mg on day 1
and 900 mg on day 2). For the 140 patients for whom
these mitigation measures were implemented, 74
patients (53%) experienced a reaction with the first
1000 mg (64 patients on day 1, 3 patients on day 2,
and 7 patients on both days) and < 3% thereafter
[see Dosage and Administration (2)].
Non-Hodgkin Lymphoma
Overall, 69% of patients experienced an infusion
reaction (all grades) during treatment with GAZYVA
in combination with bendamustine. The incidence
of Grade 3-4 infusion reactions was 11%. In Cycle
1, the incidence of infusion reactions (all grades) was
55% in patients receiving GAZYVA in combination
with bendamustine with Grade 3-4 infusion reactions
reported in 9%. In patients receiving GAZYVA in
combination with bendamustine, the incidence of
infusion reactions was highest on Day 1 (38%), and
gradually decreased on Days 2, 8 and 15 (25%, 7%
and 4%, respectively).
During Cycle 2, the incidence of infusion reactions
was 24% in patients receiving GAZYVA in
combination with bendamustine and decreased with
subsequent cycles.
During GAZYVA monotherapy, infusion reactions (all
grades) were observed in 8% of patients. No grade
3-4 infusion reactions were reported during GAZYVA
monotherapy.
Overall, 2% of patients experienced an infusion
reaction leading to discontinuation of GAZYVA.
Neutropenia:
Chronic Lymphocytic Leukemia
The incidence of neutropenia reported as an



Table of Contents for the Digital Edition of ASH News Daily 2016 - Issue 1

Contents
ASH News Daily 2016 - Issue 1 - A-1
ASH News Daily 2016 - Issue 1 - A-2
ASH News Daily 2016 - Issue 1 - A-3
ASH News Daily 2016 - Issue 1 - A-4
ASH News Daily 2016 - Issue 1 - A-5
ASH News Daily 2016 - Issue 1 - A-6
ASH News Daily 2016 - Issue 1 - A-7
ASH News Daily 2016 - Issue 1 - A-8
ASH News Daily 2016 - Issue 1 - A-9
ASH News Daily 2016 - Issue 1 - A-10
ASH News Daily 2016 - Issue 1 - A-11
ASH News Daily 2016 - Issue 1 - A-12
ASH News Daily 2016 - Issue 1 - A-13
ASH News Daily 2016 - Issue 1 - A-14
ASH News Daily 2016 - Issue 1 - A-15
ASH News Daily 2016 - Issue 1 - A-16
ASH News Daily 2016 - Issue 1 - A-17
ASH News Daily 2016 - Issue 1 - A-18
ASH News Daily 2016 - Issue 1 - A-19
ASH News Daily 2016 - Issue 1 - A-20
ASH News Daily 2016 - Issue 1 - A-21
ASH News Daily 2016 - Issue 1 - A-22
ASH News Daily 2016 - Issue 1 - A-23
ASH News Daily 2016 - Issue 1 - A-24
ASH News Daily 2016 - Issue 1 - A-25
ASH News Daily 2016 - Issue 1 - A-26
ASH News Daily 2016 - Issue 1 - Contents
ASH News Daily 2016 - Issue 1 - B-2
ASH News Daily 2016 - Issue 1 - B-3
ASH News Daily 2016 - Issue 1 - B-4
ASH News Daily 2016 - Issue 1 - B-5
ASH News Daily 2016 - Issue 1 - B-6
ASH News Daily 2016 - Issue 1 - B-7
ASH News Daily 2016 - Issue 1 - B-8
ASH News Daily 2016 - Issue 1 - B-9
ASH News Daily 2016 - Issue 1 - B-10
ASH News Daily 2016 - Issue 1 - B-11
ASH News Daily 2016 - Issue 1 - B-12
ASH News Daily 2016 - Issue 1 - B-13
ASH News Daily 2016 - Issue 1 - B-14
ASH News Daily 2016 - Issue 1 - B-15
ASH News Daily 2016 - Issue 1 - B-16
ASH News Daily 2016 - Issue 1 - B-17
ASH News Daily 2016 - Issue 1 - B-18
ASH News Daily 2016 - Issue 1 - B-19
ASH News Daily 2016 - Issue 1 - B-20
ASH News Daily 2016 - Issue 1 - B-21
ASH News Daily 2016 - Issue 1 - B-22
ASH News Daily 2016 - Issue 1 - B-23
ASH News Daily 2016 - Issue 1 - B-24
ASH News Daily 2016 - Issue 1 - B-25
ASH News Daily 2016 - Issue 1 - B-26
ASH News Daily 2016 - Issue 1 - B-27
ASH News Daily 2016 - Issue 1 - B-28
ASH News Daily 2016 - Issue 1 - B-29
ASH News Daily 2016 - Issue 1 - B-30
ASH News Daily 2016 - Issue 1 - B-31
ASH News Daily 2016 - Issue 1 - B-32
ASH News Daily 2016 - Issue 1 - B-33
ASH News Daily 2016 - Issue 1 - B-34
ASH News Daily 2016 - Issue 1 - B-35
ASH News Daily 2016 - Issue 1 - B-36
ASH News Daily 2016 - Issue 1 - B-37
ASH News Daily 2016 - Issue 1 - B-38
ASH News Daily 2016 - Issue 1 - B-39
ASH News Daily 2016 - Issue 1 - B-40
ASH News Daily 2016 - Issue 1 - B-41
ASH News Daily 2016 - Issue 1 - B-42
ASH News Daily 2016 - Issue 1 - B-43
ASH News Daily 2016 - Issue 1 - B-44
ASH News Daily 2016 - Issue 1 - B-45
ASH News Daily 2016 - Issue 1 - B-46
ASH News Daily 2016 - Issue 1 - B-47
ASH News Daily 2016 - Issue 1 - B-48
ASH News Daily 2016 - Issue 1 - C-1
ASH News Daily 2016 - Issue 1 - C-2
ASH News Daily 2016 - Issue 1 - C-3
ASH News Daily 2016 - Issue 1 - C-4
ASH News Daily 2016 - Issue 1 - C-5
ASH News Daily 2016 - Issue 1 - C-6
ASH News Daily 2016 - Issue 1 - C-7
ASH News Daily 2016 - Issue 1 - C-8
ASH News Daily 2016 - Issue 1 - C-9
ASH News Daily 2016 - Issue 1 - C-10
ASH News Daily 2016 - Issue 1 - C-11
ASH News Daily 2016 - Issue 1 - C-12
ASH News Daily 2016 - Issue 1 - C-13
ASH News Daily 2016 - Issue 1 - C-14
ASH News Daily 2016 - Issue 1 - C-15
ASH News Daily 2016 - Issue 1 - C-16
ASH News Daily 2016 - Issue 1 - C-17
ASH News Daily 2016 - Issue 1 - C-18
ASH News Daily 2016 - Issue 1 - C-19
ASH News Daily 2016 - Issue 1 - C-20
ASH News Daily 2016 - Issue 1 - C-21
ASH News Daily 2016 - Issue 1 - C-22
ASH News Daily 2016 - Issue 1 - C-23
ASH News Daily 2016 - Issue 1 - C-24
ASH News Daily 2016 - Issue 1 - C-25
ASH News Daily 2016 - Issue 1 - C-26
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