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.

• Authors: Mikkael A Sekeres, Jaroslaw P Maciejewski, Aristotle A N Giagounidis, Kenton Wride, Robert Knight, Azra Raza, Alan F List
• Journal: Journal of clinical oncology : official journal of the American Society of Clinical Oncology (J Clin Oncol) Vol. 26 Issue 36 Pg. 5943-9 (Dec 20 2008) ISSN: 1527-7755 [Electronic] United States
• PMID: 19018091 (Publication Type: Clinical Trial, Phase II, Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)

Chemical References

• Antineoplastic Agents
• Thalidomide
• Lenalidomide

Topics

• Adult
• Aged
• Aged, 80 and over
• Antineoplastic Agents (adverse effects, therapeutic use)
• Erythrocyte Transfusion
• Female
• Humans
• Lenalidomide
• Male
• Middle Aged
• Myelodysplastic Syndromes (drug therapy, genetics, therapy)
• Neutropenia (chemically induced)
• Thalidomide (analogs & derivatives, therapeutic use)
• Thrombocytopenia (chemically induced)