Novel Treatment of Biologic and Molecular Targets for MDS-related Anemias and Higher Risk ...

42 Pages·2016·1.82 MB·English

by  Uwe Platzbecker

Novel Treatment of Biologic and Molecular Targets for
MDS-related Anemias and Higher Risk Disease

Uwe Platzbecker

D·MDS
Medizinische Klinik und Poliklinik I
Deutsche MDS-Studiengruppe
Universitätsklinikum „Carl Gustav Carus“ Dresden, Germany
Disclosure
I have the following financial relationships:

• Consultant:
Amgen, Celgene, Janssen, Novartis

• Research support:
Amgen, Celgene, Janssen, Novartis
MDS as a disease model of leukemogenesis
Normal Low-risk MDS High-risk MDS AML
years
MDS as a disease model of leukemogenesis
Normal Low-risk MDS High-risk MDS AML
Genetic „Hit“
years
Classification
quantitative
Normal Low-risk MDS High-risk MDS AML
% blasts
Molecular Classification
Targets?

Normal Low-risk MDS High-risk MDS AML
Papaemmanuil et al. Blood 2013
Therapeutic principles
Normal Low-risk MDS High-risk MDS AML
Stimulation
Suppression
Therapy lower-risk MDS
Normal Low-risk MDS High-risk MDS AML
Erythropoiesis-stimulating agents (ESA)
ESA Registration Trials in MDS
EPO-a 40-80.000 E qw
vs PLACEBO
• IPSS low/int-1
R
• EPO<500
• <=4 RBCs/8 W.
Darbepoetin 500 q3w
vs PLACEBO
Fenaux et al. EHA 2016, Platzbecker et al. EHA 2016
Darbepoetin-trial
Transfusions

p = 0.008
4 100 3 100
7
2
-
- 59.2% 0
5
3
sk 80 (29 / 49) s 80
e k 50.8%
e
e
e
W 60 36.1% W 60 (64 / 126)

d (35 / 97) d
e
e
s
u 40 s 40
u
f
sn fs
n
a
a
rT 20 r 20
T

%
%
0 0

D arbepoetin alfa
Placebo D arbepoetin alfa

2 4 -w e e k D o u b le -b lin d 4 8 -w e e k O p e n -la b e l

Platzbecker et al. EHA 2016