Relationship of treatment-related cytopenias and response to lenalidomide in patients with lower-risk myelodysplastic syndromes.
OBJECTIVE
Patients with myelodysplastic syndromes (MDS) often require treatment with growth factors (GFs) or non-GF therapies. One non-GF drug, lenalidomide, is particularly effective at achieving transfusion independence (TI) in patients with lower-risk MDS with the del(5q) cytogenetic abnormality. However, approximately half of del(5q) patients and one quarter of non-del(5q) patients treated with lenalidomide experience significant cytopenias. Lenalidomide-induced cytopenias occurring early in treatment may serve as a surrogate marker of clonal suppression and, therefore, may be predictive of a TI response.


METHODS
We analyzed 362 low-risk, transfusion-dependent patients with MDS, with or without the del(5q) abnormality, enrolled in two phase II studies (MDS-003 and MDS-002) to determine whether treatment-related cytopenias are correlated with lenalidomide response. Cytopenias were assessed during the first 8 weeks of therapy, and response was defined as TI; response predictors were explored in univariate and multivariate analyses.


RESULTS
Among patients with del(5q), 70% of those whose platelet count decreased by > or = 50% achieved TI, as compared with 42% of those whose platelet count remained stable or declined by less than 50% (P = .01). Among patients without baseline neutropenia, 82% of those whose absolute neutrophil count (ANC) decreased by > or = 75% achieved TI, as compared with 51% whose ANC remained stable or decreased by less than 75% (P = .02). These relationships were consistent in multivariate analyses. No relationship between the development of cytopenias and response could be established for lower-risk patients with MDS without del(5q).


CONCLUSIONS
These findings support the hypothesis that a direct cytotoxic effect of lenalidomide specific to the del(5q) clone may be indicative of a TI response.
Sekeres
Mikkael A
MA
Department of Hematologic Oncology and Blood Disorders, Cleveland Clinic Taussig Cancer Institute, Desk R35, 9500 Euclid Ave, Cleveland, OH 44195, USA. sekerem@ccf.org
Maciejewski
Jaroslaw P
JP
Giagounidis
Aristotle A N
AA
Wride
Kenton
K
Knight
Robert
R
Raza
Azra
A
List
Alan F
AF
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000970:Antineoplastic Agents / Q000009:adverse effects* / Q000627:therapeutic use*; D017707:Erythrocyte Transfusion; D005260:Female; D006801:Humans; D000077269:Lenalidomide; D008297:Male; D008875:Middle Aged; D009190:Myelodysplastic Syndromes / Q000188:drug therapy* / Q000235:genetics / Q000628:therapy; D009503:Neutropenia / Q000139:chemically induced*; D013792:Thalidomide / Q000031:analogs & derivatives* / Q000627:therapeutic use; D013921:Thrombocytopenia / Q000139:chemically induced*
D000970:Antineoplastic Agents; D013792:Thalidomide; D000077269:Lenalidomide