Abstract

Introduction

Lenalidomide (LEN) is the standard of care for treatment of transfusion dependent lower risk myelodysplastic syndromes (MDS) with chromosome 5q deletion (del 5q). In the MDS-002 study, 26% of lower risk transfusion dependent MDS patients became red blood cell transfusion independent after LEN treatment. National Comprehensive Cancer Network (NCCN) clinical guidelines list LEN as a second line treatment alternative for transfusion dependent anemia in lower risk non-del 5q MDS after azanucleosides failure. The response rate to LEN after azanucleosides failure, however, is not known given that the MDS-002 study preceded FDA approval of azanucleosides. To address the best sequence of LEN to optimize response potential in lower risk MDS, we examined the response rates to LEN in non-del 5q lower risk MDS when offered as first line after (erythroid stimulating agents) ESA's or after azacitidine failure.

Methods

This was a retrospective study conducted using the Moffitt Cancer Center (MCC) MDS database. We identified patients with lower risk MDS who received both LEN and azacitidine as first or second line therapy after erythroid stimulating agents. Lower risk MDS was defined according to the international prognostic scoring system (IPSS) Low or intermediate-1 (int-1) risk groups. The primary endpoint was to compare rates of erythroid hematological improvement (HI-E) between the group of patients who received LEN as first line therapy followed by azacitidine as second line (LEN 1st line group) and those who received LEN as second line therapy after azacitidine (LEN 2nd line group). HI was defined according to international working group criteria (IWG 2006). Chi- square test was used for categorical variables, T-test was used for continuous variables, and Kaplan Meier estimates for overall survival. All analyses were conducted using SPSS statistical software (IBM version 21)

Results

We identified 63 patients who received both azacitidine and LEN as first and second line where 37 patients were in group 1 (LEN 1st line) and 26 patients were in group 2 (LEN 2nd line). Baseline characteristics between the two groups are summarized in Table-1. There were no statistically significant differences between the 2 groups in terms of mean age at diagnosis, gender, WHO subtype, revised IPSS, or mean blood counts. The majority of patients had refractory cytopenia with multilineage dysplasia (RCMD) and had low risk revised IPSS .

Table-1

Baseline characteristics

  Len 1st line
(n=37) 
Len 2nd line
(n=26) 
P-value 
AGE Mean 66.3 65.7 0.85 
Gender Male 26 (70%) 18 (69%) 0.6 
 Female 11 (30%) 8 (31%) 
WHO subtype RA
RARS
RCMD
RAEB-1
CMML
MDS/MPN 
4 (11%)
9 (24%)
14 (38%)
5 (14%)
2 (5%)
3 (8%) 
4 (15%)
7 (27%)
13 (50%)
1 (4%)
1 (4%)
0.3 
Revised IPSS Very low
Low
Intermediate
High
Very High 
4 (11%)
20 (57%)
8 (23%)
3 (9%)
5 (19%)
17 (65%)
3 (12)
0
1 (4%) 
0.25 
CBC Hgb (g/dl)
Platelets
ANC 
9.1
236
2.8 
9.1
233
2.3 
0.9
0.9
0.47 
  Len 1st line
(n=37) 
Len 2nd line
(n=26) 
P-value 
AGE Mean 66.3 65.7 0.85 
Gender Male 26 (70%) 18 (69%) 0.6 
 Female 11 (30%) 8 (31%) 
WHO subtype RA
RARS
RCMD
RAEB-1
CMML
MDS/MPN 
4 (11%)
9 (24%)
14 (38%)
5 (14%)
2 (5%)
3 (8%) 
4 (15%)
7 (27%)
13 (50%)
1 (4%)
1 (4%)
0.3 
Revised IPSS Very low
Low
Intermediate
High
Very High 
4 (11%)
20 (57%)
8 (23%)
3 (9%)
5 (19%)
17 (65%)
3 (12)
0
1 (4%) 
0.25 
CBC Hgb (g/dl)
Platelets
ANC 
9.1
236
2.8 
9.1
233
2.3 
0.9
0.9
0.47 

The rate of HI-E was 38% (n=14) among LEN 1st line group compared to 12% (n=3) in LEN 2nd line group. (p=0.04). There was no difference in overall survival (OS) among the two groups with a median OS of 104 months and 87 months, respectively, p=0.55. There was no difference in AML transformation rate, 5.4% (n=2) and 11% (n=3) among the two groups, respectively, p=0.33. There were no differences in response rates to azacitidine among the two groups. Among the Len 1st line group response to 2nd line azacitidine was 38% (n=14) compared to 35% (n=9) among those who received azacitidine as first line followed by LEN as 2nd line. (p=0.69).

Conclusion

LEN yields a higher rate of HI-E in non-del 5q lower risk MDS when used as first line therapy. If validated in a larger cohort, LEN should be considered for 1st line therapy after ESAs rather than after azacitidine failure. Responses to azacitidine were similar among the two groups, indicating no adverse effect of LEN on azacitidine response.

Disclosures:

Komrokji:Celgene: Research Funding, Speakers Bureau. Off Label Use: use of lenalidomide in non del 5q. Lancet:Celgene: Research Funding. List:Celgene: Research Funding.

Author notes

*

Asterisk with author names denotes non-ASH members.

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