Originally published as JCO Early Release 10.1200/JCO.2007.15.5770 on November 17 2008

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

Mikkael A. Sekeres, Jaroslaw P. Maciejewski, Aristotle A.N. Giagounidis, Kenton Wride, Robert Knight, Azra Raza, Alan F. List

From the Cleveland Clinic Taussig Cancer Center, Cleveland, OH; St Johannes Hospital, Duisburg, Germany; Celgene Corporation, Summit, NJ; St Vincent's Medical Center, New York, NY; and H. Lee Moffitt Cancer Center, Tampa, FL

Corresponding author: Mikkael A. Sekeres, MD, MS, Department of Hematologic Oncology and Blood Disorders, Cleveland Clinic Taussig Cancer Institute, Desk R35, 9500 Euclid Ave, Cleveland, OH 44195; e-mail: sekerem{at}ccf.org

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.

published online ahead of print at www.jco.org on November 17, 2008.

Supported in part by National Institutes of Health Grant No. U54RR19397-03 (M.A.S., J.P.M., and A.F.L.) and by research funding from Celgene Corporation to M.A.S.

Presented in part at the Ninth International Symposium on Myelodysplastic Syndromes, May 16-19, 2007, Florence, Italy, and at the American Society of Hematology Annual Meeting, December 11, 2007, Atlanta, GA, and published in abstract form at the meetings.

Authors’ disclosures of potential conflicts of interest and author contributions are found at the end of this article.

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