Disease briefing of autoimmune hemolytic anemia - CAD.

1. By
Will
Roettger
Principal
Consultant
20/20
Market
Insights,
LLC
July
12,
2013

2. Will
Roettger
is
an
established
career
professional
in
the
pharmaceutical
and
biotech
industry.
Having
worked
for
Novartis,
AstraZeneca,
Merck,
Alexion,
and
Dendreon
he
has
developed
expertise
across
the
therapeutic
areas
of
oncology,
hematology,
and
immunology
for
pipeline
and
launch
products.
He
has
been
instrumental
in
establishing
marketing
intelligence
as
a
core
capability
in
support
of
clinical
and
commercial
new
product
development,
solving
the
many
commercial
challenges
that
high-­‐priced
specialty
products
face
from
a
patient,
provider,
and
investor
perspective.
Additionally
he
has
supported
two
specialty
product
launches,
providing
actionable
insights
and
recommendations
by
integrating
market
research
findings
with
competitive
intelligence.
As
a
principal
for
20/20
Market
Insights,
LLC,
he
is
dedicated
to
providing
clients
with
clear
vision
into
competitor
landscapes,
strategies,
and
product
assessments
that
drive
strategic
business
decisions
in
new
drug
development.
Contact
Information:
Will
Roettger
Principal
Consultant
20/20
Market
Insights,
LLC
908-­‐391-­‐4362
will.roettger@gmail.com
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5. AIHA
is
the
immunologic
destruction
of
RBCs
mediated
by
auto-­‐antibodies
against
antigens
on
the
RBC
surface.
They
are
classified
by
isotype
(IgG,
IgM,
IgA)
and
the
temperature
at
which
they
maximally
react
5

6. Acquired
Hemolytic
Anemia
Immune
Hemolytic
Anemia
(most
common
form)
Non-­‐Immune
Hemolytic
Anemia
!
!
!
(1:80,000)
Autoimmune
(AIHA)
(1:300,000)
(50%)
! Idiopathic
! PCH
Alloimmune
!
!
(1:100,000)
Cold
Antibody
(13-­‐25%)
Primary
Drug
Induced
Infection
Induced
Mechanical
Trauma
Paroxysmal
Nocturnal
Hemoglobinuria
(PNH)
MAHA
(TTP,
HUS,
aHUS)
Toxins
Secondary
(50%)
! Infectious
Mononucleosis
! Lymphoma
Warm
Antibody
(50-­‐70%)
! Idiopathic
(ITP)
! Systemic
Lupus
Erythematosus
(SLE)
! Evan’s
Syndrome
Hemolytic
Disease
of
the
Newborn
(HDN)
Blood
Transfusion
Reactions
Sources:
Kelton,
AHA
10.
ICD-­‐10
Disease
of
Blood
D55-­‐D59.
http://en.wikipedia.org/
wiki/Acquired_hemolytic_anemia.
Haematologica
2006;
91:460-­‐466
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10. Source:
Acquired
Hemolytic
Syndrome,
Chapter
10,
JG
Kelton.
J.
Rogers,
UNC
Internal
Medicine,
GR
Slides,
2008
10

11. Source:
Acquired
Hemolytic
Syndrome,
Chapter
10,
JG
Kelton.
J.
Rogers,
UNC
Internal
Medicine,
GR
Slides,
2008
11

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13. Source:
AHA
10
13

14. Intravascular Hemolysis
Extra-vascular Hemolysis
Mechanism
Red cell destruction in the
intravascular compartment resulting
in hemoglobin being released into the
plasma
Red cells are recognized as foreign or
become more rigid and are sequestered in
the spleen with subsequent phagocytosis
Possible Causes
Complement, toxins, membrane
defects, enzyme deficiencies, drugs
Immunoglobulin, complement, membrane
defects
• Hemoglobinemia
Present
Absent/present in severe cases
• Hemoglobinuria
Present
Absent/present in severe cases
• Haptoglobin
Reduced or absent
Normal or Reduced
• Methemalbumin
Present
Absent
• Hemosidinuria
Present
Absent
• LDH
Grossly elevated
Elevated
• Jaundice
Present
Present
• Splenomegaly
Absent
Present
• Blood Film
Schistocytes. Helmet cells,
fragmented red cells
Spherocytes, erythrophagocytosis
Laboratory Feature
Source:
AHA
10
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17. Rituxan
(375
mg/m2)
+
Fludarabine
(40
mg/m2)
–
Berensten,
et.al.
2010
Response Level
Frequency
Hb Level
IgM Concentration
(Median, g/dL)
(Median, % of Baseline)
(n)
(%)
22
76
CR
6
21
+4.0
-81
PR
16
55
+3.1
-76
NR
7
24
-0.2
-27
29
100
+2.5
-71
Response Rate
TOTAL
Median Time To Response:
4 months
Response Duration:
>66 months
Grade 3-4 Hematologic Toxicity:
41%
• CR
=
absence
of
anemia
,
no
signs
of
hemolysis,
no
clinical
symptoms
of
CAD,
undetectable
serum
monoclonal
protein,
and
no
signs
of
clonal
lymphyproliferation
by
bone
marrow
histology,
immunohistochemistry
and
flow
cytometry.
• PR
=
stable
increase
in
Hb
levels
by
at
least
2.0
g/dL
or
to
the
normal
range,
combined
with
a
reduction
in
serum
IgM
concentrations
by
at
least
50%
or
to
the
normal
range,
improvement
of
clinical
symptoms,
transfusion
independency
• NR
=
patients
not
meeting
CR
or
PR.
Source:
NCT00373595
(Blood
2010;116(17):3180-­‐3184
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20. Will
Roettger
Principal
Consultant
20/20
Market
Insights,
LLC
908-­‐391-­‐4362
will.roettger@gmail.com
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