Relationship of Treatment-Related Cytopenias and Response to Lenalidomide in Patients With Lower-Risk Myelodysplastic Syndromes

Purpose 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. Patients and 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 >= 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 >= 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). Conclusion 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.