Abstract

Introduction

The “classical” IPSS, based on cytogenetics, marrow blast percentage, and number of cytopenias, has played a major role in prognosis assessment in MDS. The recently published revised IPSS (IPSS-R), refines the original IPSS prognostic value (Greenberg et al, Blood 2012). However, its prognostic value for response to ESA has not been assessed. We analyzed it retrospectively in 456 IPSS Low-/Int-1-risk MDS patients (pts) treated with ESA in France, Germany and Italy.

Results

Those 456 pts had serum EPO < 500mU/ml and Hb≤10g/dl, and had received ESA (EPO alfa or beta 40000-60000 IU/week, or darbepoietin 150 - 300µg/week) for at least 12 weeks. In addition to IPSS-R parameters, age, sex, serum EPO level, serum ferritin (SF), and RBC transfusion requirement before ESA onset were assessed for response to ESA (based on IWG 2006 criteria), and overall survival (OS) from ESA onset. Characteristics of the 456 pts at ESA onset are listed in Table 1. 71% of the pts had never received RBC transfusions, with a median Hb level of 9.3g/dl (range 7.0-10) , and 29% pts had received at least 4 RBC concentrates/8wks before ESA onset (with a maximum of 12). Median SF was 357ng/ml and serum EPO 60mU/ml (range 6-483). IPSS was low in 55% and intermediate-1 in 45% pts. IPSS-R was very low in 15%, low in 61%, intermediate in 19% and high in 4% of the pts.

Table 1

Baseline patient characteristics. * 109/L.

Univariate and multivariate analyses for response (IWG 2006 criteria).

 n=456 % of pts Erythroid response ( IWG 2006 criteria) Univariate analysis p Multivariate analysis p 
Hb g/dl      
<8 52 11% 33   
8-10 292 64% 66   
=10 112 25% 78 <0.0001  
ANC      
<0.8 42 9% 55   
≥0.8 414 91% 66 0.16  
Platelet *      
<50 17 3% 37   
50-100 58 13% 57   
>100 381 84% 67 0.01  
Marrow blasts, %      
≤2 238 52% 72   
<2-<5 118 26% 61   
5-10 100 22% 53 0.0052  
IPSS-R karyotype      
very good 21 5% 71   
good 379 83% 65   
intermediate 45 10% 75   
poor-very poor 11 2% 20 0.008  
IPSS      
low 256 55% 72   
Int-1 210 45% 52 0.001  
IPSS-R      
very low 69 15% 85   
low 281 61% 68   
intermediate 87 19% 48   
high 19 4% 31 <0.0001 0.008 
Sex      
male 250 55% 62   
female 206 45% 68 0.14  
Age      
≤60 29 6% 55   
>60 427 94% 66 0.23  
EPO, mU/ml      
≤200 393 86% 75   
>200 63 13% 31 <0.0001 <0.0001 
SF, ng/ml      
≤350 224 49% 72   
>350 232 51% 58 0.001 0.01 
Previous RBC transfusions      
no 323 71% 73   
yes 133 29% 55 0.0005 0.001 
WHO      
RA 110 24% 73   
RAEB-1 69 15% 50   
RARS 114 25% 70   
RARS-T 0.3% 100   
RCMD 124 27% 62   
MDS WITH DEL 5q 21 5% 62   
MDS-U 16 4% 55 0.03 0.71 
 n=456 % of pts Erythroid response ( IWG 2006 criteria) Univariate analysis p Multivariate analysis p 
Hb g/dl      
<8 52 11% 33   
8-10 292 64% 66   
=10 112 25% 78 <0.0001  
ANC      
<0.8 42 9% 55   
≥0.8 414 91% 66 0.16  
Platelet *      
<50 17 3% 37   
50-100 58 13% 57   
>100 381 84% 67 0.01  
Marrow blasts, %      
≤2 238 52% 72   
<2-<5 118 26% 61   
5-10 100 22% 53 0.0052  
IPSS-R karyotype      
very good 21 5% 71   
good 379 83% 65   
intermediate 45 10% 75   
poor-very poor 11 2% 20 0.008  
IPSS      
low 256 55% 72   
Int-1 210 45% 52 0.001  
IPSS-R      
very low 69 15% 85   
low 281 61% 68   
intermediate 87 19% 48   
high 19 4% 31 <0.0001 0.008 
Sex      
male 250 55% 62   
female 206 45% 68 0.14  
Age      
≤60 29 6% 55   
>60 427 94% 66 0.23  
EPO, mU/ml      
≤200 393 86% 75   
>200 63 13% 31 <0.0001 <0.0001 
SF, ng/ml      
≤350 224 49% 72   
>350 232 51% 58 0.001 0.01 
Previous RBC transfusions      
no 323 71% 73   
yes 133 29% 55 0.0005 0.001 
WHO      
RA 110 24% 73   
RAEB-1 69 15% 50   
RARS 114 25% 70   
RARS-T 0.3% 100   
RCMD 124 27% 62   
MDS WITH DEL 5q 21 5% 62   
MDS-U 16 4% 55 0.03 0.71 

303 (61%) pts had an erythroid response (ER), including 72% and 52% of low and int-1 risk pts respectively (p=0.001). Using IPSS-R, 85%, 68%, 48% and 31% of pts had ER in the very low, low, intermediate and high risk group respectively (p<0.0001).

Other prognostic factors of ER, in univariate analysis, included individual IPSS-R parameters analyzed according to IPSS-R thresholds (Hb level, platelet count, ANC, marrow blast %, cytogenetics) serum EPO level, SF (variables tested as continuous variables) and previous RBC-transfusions. In multivariate analysis, IPSS-R, serum EPO, and SF remained significantly associated with ER (p<0.0001, p=0.002 and p<0.0001 respectively).

Applying 1 point to each of the following unfavorable variables of ER: serum EPO >200mU/ml (=1), SF >350 ng/ml (=1), IPSS-R (very low=0, low=1, intermediate=2 and high=3), yielded a score ranging from 0 to 4, with ER rates of 85%, 80%, 64%, 40% and 20% respectively. As expected, IPSS-R also had strong prognostic value for OS (not shown).

Conclusion

In this patient cohort with overall favorable prognostic factors of response to ESA according to the Nordic score (ie serum EPO <500 mU/ml and no or limited transfusion dependence, Hellstrom-Lindberg et al BJH 2003), IPSS-R alone, and even better, a score >=3 (using IPSS-R, serum EPO and SF) proved useful to identify pts with low response to ESA, who also have worse OS and may require alternative treatments (Kelaidi et al, Leukemia 2013).

Disclosures:

No relevant conflicts of interest to declare.

Author notes

*

Asterisk with author names denotes non-ASH members.

This icon denotes a clinically relevant abstract