Calendar
2019 ASTRO Annual Meeting
ASH Meeting on Hematologic Malignancies
September 15 – 18, 2019
Chicago, IL
The annual meeting of the American Society for
Radiation Oncology provides a forum for more than
11,000 attendees to discuss the translation of scientific
discoveries into clinical applications and opportunities
for cure.
September 6 – 7, 2019
Chicago, IL
Top experts in hematologic malignancies discuss the
latest developments in clinical care and provide answers
to challenging patient care questions in a small-group
setting. The program content is structured as “How I Treat”
presentations, which showcase each speaker’s evidence-
based treatment approaches.
product, 76% and 73%, respectively, completed
the full course. Dose modification due to adverse
reactions occurred in 74% of the GAZYVA arm
and 63% of the rituximab product arm throughout
study treatment, and discontinuation of any study
drug due to adverse reactions occurred in 18% and
15%, respectively.
Throughout treatment and follow-up, the most
common adverse reactions (incidence ≥ 20%)
observed at least 2% more in the GAZYVA arm
included infusion related reactions, neutropenia,
upper respiratory tract infection, cough,
constipation and diarrhea (Table 8). Neutropenia,
infusion related reactions, febrile neutropenia and
thrombocytopenia were the most common Grade 3
to 5 adverse reactions (incidence ≥ 5%) observed
more frequently in the GAZYVA arm.
ophthalmic herpes simplex, ophthalmic herpes zoster,
oral herpes, varicella, varicella zoster virus infection.
Pneumonia includes pneumonia bacterial,
pneumonia haemophilus, pneumonia
pneumococcal, pneumonia fungal, pneumocystis
jirovecii infection, pneumocystis jirovecii
pneumonia, atypical pneumonia, lung infection,
pneumonia, pneumonia aspiration, lung infiltration.
Cough includes cough, productive cough, upper-
airway cough syndrome.
Diarrhea includes diarrhea, defecation urgency,
frequent bowel movement, gastroenteritis,
gastroenteritis viral.
Headache includes cluster headache, headache,
sinus headache, tension headache, migraine.
Insomnia includes initial insomnia, insomnia, sleep
disorder.
Pruritus includes pruritus and pruritus generalized.
During the monotherapy period, the common
adverse reactions (incidence ≥ 10%) observed at
least 2% more with GAZYVA were upper respiratory
tract infection (40%), cough (23%), musculoskeletal
pain (20%), neutropenia (19%) and herpesvirus
infection (13%).
Table 9 summarizes treatment-emergent laboratory
abnormalities during treatment and follow-up.
The Grade 3 to 4 abnormalities reported at least
2% more in the GAZYVA arm were lymphopenia,
leukopenia, neutropenia, thrombocytopenia and
hyperuricemia. Patients in the GAZYVA arm, as
compared to the rituximab product arm, had higher
incidences of Grade 4 neutropenia (38% vs. 30%,
respectively), Grade 4 lymphopenia (33% vs. 22%),
and Grade 4 leukopenia (17% vs. 12%).
Table 8 Common Adverse Reactions (≥ 10%
Incidence and ≥ 2% Greater in the GAZYVA
Arm) in Patients with Previously Untreated NHL
(GALLIUM)
Body System
Adverse
Reactions a, b
GAZYVA +
chemotherapy
followed
by GAZYVA
monotherapy
n = 691 Rituximab
product +
chemotherapy
followed by
rituximab product
monotherapy
n = 694
All Grades Grades
%
3 to 5 % All Grades Grades
%
3 to 5 %
Injury, Poisoning and Procedural Complications
Infusion Related
72
12
60
8
Reaction c
Blood and Lymphatic System Disorders
53
49
47
41
Neutropenia d
Thrombocytopenia d 14
7
8
3
Table 9 Common New or Worsening Laboratory
Abnormalities (≥ 10% Incidence and ≥ 2%
Greater in the GAZYVA Arm) in Patients with
Previously Untreated NHL (GALLIUM)
Infections and Infestations
Upper Respiratory
Tract Infection
Herpesvirus
Infection 50 3 43 1
18 3 14 1
Pneumonia 14 7 12 6
Laboratory
Abnormalities a
Respiratory, Thoracic and Mediastinal Disorders
Cough
35
< 1
28
< 1
Gastrointestinal Disorders
Constipation
32
< 1
29
< 1
Diarrhea
30
3
26
16
0
14
< 1
13 0 10 < 1
Pruritus 11 < 1 9 0
Includes adverse reactions reported throughout study treatment and
follow-up.
Includes grouped preferred terms.
c
Except where noted, individual events that meet the definition of
“infusion related reaction” are excluded from Table 8 above, as they are
already included in the group term “Infusion Related Reaction”. The
most common individual terms within the group term “Infusion Related
Reaction” in decreasing order of frequency are nausea, chills, pyrexia
and vomiting.
d
Includes adverse reactions reported as infusion related reactions.
a
b
Infusion related reactions are defined as any
related adverse reaction that occurred during or
within 24 hours of infusion.
Neutropenia includes neutropenia,
agranulocytosis, febrile neutropenia,
granulocytopenia and neutrophil count decreased;
febrile neutropenia includes febrile neutropenia,
neutropenic infection, neutropenic sepsis, and
febrile bone marrow aplasia.
Thrombocytopenia includes thrombocytopenia
and platelet count decreased.
Upper respiratory tract infection includes upper
respiratory tract congestion, upper respiratory
tract inflammation, sinusitis bacterial, upper
respiratory tract infection bacterial, pharyngitis
streptococcal, sinusitis fungal, upper respiratory
fungal infection, acute sinusitis, chronic sinusitis,
laryngitis, nasopharyngitis, pharyngitis, rhinitis,
sinusitis, tonsillitis, upper respiratory tract infection,
rhinovirus infection, viral pharyngitis, viral rhinitis,
viral upper respiratory tract infection.
Herpesvirus infection includes genital herpes,
genital herpes zoster, herpes dermatitis, herpes
ophthalmic, herpes simplex, herpes simplex
pharyngitis, herpes virus infection, herpes zoster,
herpes zoster disseminated, herpes zoster infection
neurological, herpes zoster oticus, nasal herpes,
All Grades Grades
%
3 to 4 % All Grades Grades
%
3 to 4 %
ALT/SGPT
increased
AST/SGOT
increased
Hypophosphatemia
Hypoalbuminemia
Hypoproteinemia
Hypocalcemia
Hyperuricemia
Hyponatremia
Hyperkalemia
Hypernatremia
Psychiatric Disorders
Insomnia
15
< 1
12
< 1
Metabolism and Nutrition Disorders
Decreased
14
< 1
12
< 1
Appetite
Skin and Subcutaneous Tissue Disorders
Alopecia Rituximab
product +
chemotherapy
followed by
rituximab product
monotherapy
n = 694
Hematology
Lymphopenia
Leukopenia
Neutropenia
Thrombocytopenia
Chemistry
2
Nervous System Disorders
Headache
18
< 1
15
< 1
Musculoskeletal and Connective Tissue Disorders
Arthralgia
GAZYVA +
chemotherapy
followed
by GAZYVA
monotherapy
n = 691
a
97 83 95 67
92
84
68 49
59
11 89
76
50 39
50
4
50 3 43 2
44 1 41 1
36
33
32
32
28
26
23
16 5
1
0
1
28
4
1 33
25
30
26
22
20
17
13 5
1
0
1
22
3
1
0
< 1
Includes lab abnormalities, reported throughout treatment and follow-
up, that were new or worsening, or worsening from baseline unknown.
In the monotherapy phase, new-onset Grade 3 or 4
neutropenia was reported in 21% of patients in the
GAZYVA arm (Grade 4, 10%) and 17% of patients
in the rituximab product arm (Grade 4, 9%).
Infusion Reactions:
Chronic Lymphocytic Leukemia
The incidence of infusion reactions in the CLL11
study 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 in CLL11,
47 (89%) experienced an infusion reaction. After
this experience, study protocol modifications
were made to require pre-medication 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)].
XVIII International Workshop on Chronic
Lymphocytic Leukaemia
September 20 – 23, 2019
Edinburgh, Scotland
The 2019 meeting of the International Workshop on
Chronic Lymphocytic Leukaemia will bring together
expert hematologists, clinicians, and researchers to
discuss recent developments in the understanding of
disease biology and treatments.
Non-Hodgkin Lymphoma
Overall, 69% of patients in the GADOLIN study
experienced an infusion reaction (all grades)
during treatment with GAZYVA in combination
with bendamustine. The incidence of Grade 3 to 4
infusion reactions in GADOLIN 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 to 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 in GADOLIN, infusion
reactions (all grades) were observed in 8% of
patients. No Grade 3 to 4 infusion reactions were
reported during GAZYVA monotherapy.
Overall, 2% of patients in GADOLIN experienced
an infusion reaction leading to discontinuation of
GAZYVA.
In GALLIUM, 72% of patients in the GAZYVA
treated arm experienced an infusion reaction (all
grades). The incidence of Grade 3 to 4 infusion
reactions for these patients was 12%. In Cycle 1,
the incidence of infusion reactions (all grades) was
62% in the GAZYVA treated arm with Grade 3 to 4
infusion reactions reported in 10%. The incidence
of infusion reactions (all grades) was highest on Day
1 (60%), and decreased on Days 8 and 15 (9% and
6%, respectively).
During Cycle 2, the incidence of infusion reactions
(all grades) in the GAZYVA treated arm was 13%
and decreased with subsequent cycles.
During GAZYVA monotherapy treatment in
GALLIUM, infusion reactions (all grades) were
observed in 9% of patients.
Overall, 1% of patients in GALLIUM experienced
an infusion reaction leading to discontinuation of
GAZYVA.
Neutropenia:
Chronic Lymphocytic Leukemia
The incidence of neutropenia reported as an
adverse reaction in CLL11 was 38% in the GAZYVA
treated arm and 32% in the rituximab product
treated arm, with the incidence of serious adverse
reactions being 1% and < 1%, respectively (Table
4). Cases of late-onset neutropenia (occurring 28
days after completion of treatment or later) were
16% in the GAZYVA treated arm and 12% in the
rituximab product treated arm.
Non-Hodgkin Lymphoma
The incidence of neutropenia in GADOLIN was
higher in the GAZYVA plus bendamustine arm (38%)
compared to the arm treated with bendamustine
alone (32%). Cases of prolonged neutropenia
(3%) and late onset neutropenia (7%) were also
reported in the GAZYVA plus bendamustine arm.
The incidence of neutropenia was higher during
treatment with GAZYVA in combination with
bendamustine (31%) compared to the GAZYVA
monotherapy treatment phase (12%).
The incidence of neutropenia in GALLIUM was
higher in the GAZYVA treated arm (53%) compared
to the rituximab product treated arm (47%).
Cases of prolonged neutropenia (1%) and late
onset neutropenia (4%) were also reported in the
GAZYVA treated arm. The incidence of neutropenia
was higher during treatment with GAZYVA in
combination with chemotherapy (45%) compared
to the GAZYVA monotherapy treatment phase (20%).
Infection:
Chronic Lymphocytic Leukemia
The incidence of infections was similar between
GAZYVA and rituximab product treated arms.
Thirty-eight percent of patients in the GAZYVA
treated arm and 37% in the rituximab product
treated arm experienced an infection, with Grade 3
to 4 rates being 11% and 13%, respectively. Fatal
events were reported in 1% of patients in both arms.
Non-Hodgkin Lymphoma
The incidence of infection in GADOLIN was 66%
in the GAZYVA plus bendamustine arm and 56%
in the bendamustine arm, with Grade 3 to 4 events
reported in 16% and 14%, respectively. Fatal
events were reported in 3% of patients in the
GAZYVA plus bendamustine arm and 4% in the
bendamustine arm.
The incidence of infections in GALLIUM was
82% in the GAZYVA treated arm and 73% in the
rituximab product treated arm, with Grade 3 to 4
events reported in 21% and 17%, respectively. In
the GAZYVA arm, fatal infections occurred in 2% of
patients compared to <1% in the rituximab product
arm.