Relationship of treatment-related cytopenias and response to lenalidomide in patients with lower-risk myelodysplastic syndromes

Abstract

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 > 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).

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.

Fig 1.

RBC transfusion independence (TI) response for del(5q) patients with and without thrombocytopenia at baseline, comparing patients who develop significant treatment-related thrombocytopenia (platelet count decline ≥ 50%) with those who do not (platelet count decline < 50%). P < .01 for platelet count decline ≥ 50% v platelet count decline less than 50%, regardless of baseline platelet level.

Fig 2.

RBC transfusion independence (TI) response for del(5q) patients with and without neutropenia at baseline, comparing patients who develop significant treatment-related neutropenia (absolute neutrophil count [ANC] decline ≥ 75%) with those who do not (ANC decline < 75%).