Prevalence of Anemia and Treatment with
Erythropoietic Agents in Patients with
Multiple Myeloma
Heinz Ludwig
Wilhelminenspital, Vienna
Austria
Heinz.ludwig@wienkav.at
European Cancer Anaemia Survey (ECAS):
Prospective Evaluation of Anemia in 15,367 Cancer Patients
Main goals:
Prevalence of anemia
Incidence of anemia
Influence of Hb on QOL
Risk factors for anemia
Treatment practice
Heinz Ludwig, Simon Van Belle, Peter Barrett-Lee, Gunnar Birgegård, Carsten Bokemeyer, Pere Gascón, Paris
Kosmidis, Maciej Krzakowski, Johan Nortier, Patrizia Olmi, Maurice Schneider, Dirk Schrijvers
Eur. J. Cancer, 2004
Analysis of the Multiple Myeloma Subset of the
European Cancer Anemia Survey (ECAS)
Questions
Prevalence of anemia at baseline
Proportion of patients ,ever anemic`
Patients were followed
up to 6 months
Incidence of anemia
Impact of age
Prediction of Anemia
Treatment patterns
Characteristics of Patient with Multiple Myeloma at
Enrollment
Number of Patients
704
Age, years
Mean
65.7
Gender, n (%)
M
322
(51.6)
F
312
(48.4)
Disease status,* n (%)
Newly diagnosed with treatment
102
(14.6)
Newly diagnosed without treatment
93
(13.3)
Persistent/recurrent
381
(54.7)
In remission
121
(17.4)
Treatment status, n (%)
Without treatment
318
(46.2)
Chemotherapy
341
(49.5)
Radiotherapy
14
(2.0)
Concomitant CT/RT
16
(2.3)
Age Distribution at Enrolment (N=704)
72.3%
45.0%
40.5%
40.0%
Age
35.0%
31.8%
Mean: 65.7
30.0%
(%) 25.0%
20.5%
20.0%
Patients 15.0%
7.2%
10.0%
5.0%
0.0%
18 - 49
50 - 59
60 - 69
> 70
Age
Prevalence and Degree of Anemia at Enrollment
in 702 patients with Multiple Myeloma
100
Mean Hb at enrollment Hb =11.0 g/dL
90
80
Prevalence of Anemia
Hb <12 g/dL = 69.2%
70
tsn 60
tie
Pa
50
39.5%
All
40
of
25.1%
30.8%
%
30
20
4.6%
10
0
<8.0
8.0 - 9.9
10.0 - 11.9
>12
Hemoglobin Categories (g/dL)
n* =
31
171
269
210
*Missing data for n = 56.
WHO Performance Status at Enrollment for
Multiple Myeloma Patients (n = 689)
100
90
Performance Status
correlates
80
43.8%
with anemia (r= -0.346)
70
tsn
60
tie
Pa
50
37.4%
39.5%
All
40
of% 30
18.7%
13.2%
20
10
0
0
1
2
3,4
WHO Performance Status
n* =
129
258
211
91
*Missing data for n = 56.
Evaluations During the Survey
Clinical Status
Follow-up Evaluations
6 months after enrollment
at Enrollment
End of Survey
Chemotherapy
Chemotherapy Cycle
6 months after enrollment
End of Survey
No Treatment
Patients Were Followed for up to 6 Months
`Ever Anemic' During the Survey by Age (N=567)
85.3% of MM patients were `ever anemic'
(69.2% had anemia at baseline)
95.0%
90.3%
Age
84.9%
85.0%
(%)
79.4%
75.0%
Patients
65.0%
60.0%
55.0%
18 - 49
50 - 59
60 - 69
> 70
Age
Hb Nadir During Survey of the 567
`Ever Anemic' Patients
58.5%
< 8
24,3%
24,5%
25,0%
8 - 8.9
9 - 9.9
19,2%
10 - 10.9
20,0%
11 - 11.9
15,0%
16,0%
15,0%
Patients
10,0%
5,0%
0,0%
< 8
8 - 8.9
9 - 9.9
10 - 10.9
11 - 11.9
Hb (g/dL)
Patients were Followed for up to 6 Months
Incidence of Anemia by Age in MM
75% of MM patients starting CT became anemic
90,0%
95,0%
85,0%
75,0%
Patients
60,0%
65,0%
MM < 60
MM > 60
55,0%
45,0%
MM < 60 years
MM > 60 years
Independent Risk Factors for Anemia
in Patients with Myeloma/Lymphoma
Predictor
Adjusted OR 95% Confidence
P - Value
Intervall
Low initial Hb
4.2
2.99 5.95
< 0.0000
Female Gender
2.8
1.99 4.07
< 0.0000
Persistent/recur
1.5
1.05 2.16
< 0.0276
rent disease
Platinum CT
5.5
2.24 13.54
< 0.0002
Birgegard G, Ludwig H, Nortier J, Schrijvers D and Gascon P
Distribution of Anemia Treatments
for MM Patients Ever Anemic (n=516)
85.3% of MM patients were `ever anemic'
2.8%
52.7%
21.0%
Trigger Hb level* for TX
Iron only
Transfusion
Epoetin: ( 9.4 g/dL)
Epoetin
No treatment
Transfusion: 8.2 g/dL
Iron only: 10.0 g/dL
23.6%
*mean
47.4% received anemia treatment
Recommendations for Erythropoietin Therapy
International Experts1
EORTC3
ASCO/ASH2
International Experts
Trigger Hb
10g/dl
10g/dl
9-11g/dl
Level
<12g/dl if on CTX or if
<12g/dl if
Symptoms
symptomatic
symptomatic
important
Target Hb
12g/dl or higher
12g/dl
12-13g/dl
Discontinue
At >14g/dl or if no
At 12g/dl or if no
If no response (6-
response (6-8wks)
response (6-8wks)
8wks)
Recommended dose
10.000 U TIW or 40.000 U
150 U/kg TIW
10.000 U TIW, or
QW
30.000 U QW, or
40.000 U QW, or
Darbepoetin
2.25µg/kg QW*
Initially non responsive
20.000U TIW
Consider dose
Dose escalation by
50%
60.000U QW
escalation
1. Ludwig,H et al. Haematol.J.2002 , 2. Rizzo,DJ et al. Blood, 2002, 3. Bockemeyer H et al, EJC 2004
Epoetin Alfa Phase IV Studies in Tumor-Associated
Anemia
Incremental Increase of QoL and Hb Level
Quality of life (100-mm LASA)
70
Glaspy
Therapeutic Window
65
Demetri
60
Gabrilove
55
50
45
Hb (g/dL)
40
7
8
9
10
11
12
13
14
Glaspy
Glaspy
267
740
918
833
308
287
223
Demetri
59
352
770
753
547
391
313
160
Gabrilove 156
466
1134
1426
844
544
410
168
Sabbatini ASCO 2000
Benefits of Treatment with Erythropoietic Agents
Increase in hemoglobin
Reduction of transfusion dependency
Substantial improvement in QoL
Exercise capacity
Apetite
Cognitive function
Is there an impact on survival ?
Treatment with Darbepoetin (2.25µ/kg once weekly) for
up to 16 Weeks had no Impact on Survival
160 Patients
Follow up: 27 months
Enrollment criterium: Hb <11g/dl
ODAC Data Base, FDA, May 4 2004
Response to Epoetin alpha Treatment Correlates with
Longer Survival in Multiple Myeloma
Retrospective Analysis (n = 32)
100
90
80
70
60
4.0 months
28.0 months
50
percentage
40
30
20
cumulative
responders
10
p<0.0001
non-responders
0
0
6
12
18
24
30
36
months survival
Summary
Prevalence of anemia in Multiple Myeloma: 69.2%
Prevalence of anemia increased with age
85.3% of patients followed for up to 6 months were anemic
at least once during the observation period (,ever anemic`)
58.3% of those ever anemic had Hb <10.g/dl
Incidence of anemia: 75% (>60 years: 90%, <60 years: 60%)
Summary
Risk factors for Anemia: Low initial Hb <9g/dl
Female gender
Persistant/recurrent disease
Platinum TX
Treatment with Erythropoietic agents has no effect on
survival
Response to Erythropoietin seems to predict for longer
survival
Benefits of Eryhropoietin Treatment: Hb, Transfusions, QoL
Erythropoietic Agents Provide Important Benefits
Thank You for Your Attention