ORIGINAL ARTICLE Lenalidomide as salvage therapy after allo-SCT for multiple myeloma is effective and leads to an increase of activated NK (NKp44 þ ) and T (HLA-DR þ ) cells M Lioznov 1 , J El-Cheikh Jr 2 , F Hoffmann 1 , Y Hildebrandt 1 , F Ayuk 1 , C Wolschke 1 , D Atanackovic 3 , G Schilling 3 , A Badbaran 1 , U Bacher 1 , B Fehse 1 , AR Zander 1 , D Blaise 2 , M Mohty 4 and N Kro¨ger 1 1 Department for Stem Cell Transplantation, University Hospital Hamburg-Eppendorf, Hamburg, Germany; 2 Unite´de Transplantation et de The´rapie Cellulaire (UTTC), Institut Paoli Calmettes, Marseille, France; 3 Department for Oncology/ Hematology, University Hospital Hamburg-Eppendorf, Hamburg, Germany and 4 CHU de Nantes, Hematologie Clinique, Universite de Nantes and INSERM, Nantes Cedex, France We investigated efficacy and toxicity of lenalidomide in 24 heavily pretreated myeloma patients with a median age of 59 years (range: 37–70) and relapse after allo-SCT. Lenalidomide was given at a dose of 15 mg (n ¼ 4), or 25 mg (n ¼ 20), orally once daily on day 1 to day 1 every 28 days, with (n ¼ 20) or without (n ¼ 4) DHAP. The median number of lenalidomide cycles was five (range: 2–17). Major side effects were leukopenia (grade 4: 4%, grade 3: 21% and grade 2: 17%) and thrombocytopenia (grade 3: 17% and grade 2: 29%); infectious complica- tions were observed in 50%. Non-hematological toxicity consisted of muscle cramps (n ¼ 9), fatigue (n ¼ 5) and constipation (n ¼ 2). Mild grade I–II GVHD was seen in three patients. Response was achieved in 66%: CR in 8%, VGPR in 8%, PR in 50% and SD in 13%. The median time to progression was 9.7 months (95% confidence interval (CI): 7.5–11.9), and median OS was 19.9 months (95% CI: 17.3–22.5). Immunomonitoring after lenalido- mide showed significant increase of activated NK (NKp44 þ ) and T (HLA-DR þ ) cells, as well as regulatory T cells (CD4 þ , CD25 þ , CD127 lo ), supporting an immunomodulating anti-myeloma effect of lenalidomide. Bone Marrow Transplantation (2010) 45, 349–353; doi:10.1038/bmt.2009.155; published online 6 July 2009 Keywords: lenalidomide; dose-reduced conditioning; allo-SCT; multiple myeloma; NK cells Introduction Allo-SCT after reduced-intensity conditioning for patients with multiple myeloma has become an effective treatment option, especially in younger patients with multiple myeloma. 1–3 To upgrade remission or to prevent or to treat relapse, several therapies such as donor lymphocyte infusions, 4,5 or novel agents such as bortezomib or thalidomide 6–9 have been investigated after allo-SCT. As the so-called ‘IMIDs’ (immunomodulatory drugs), thalido- mide and lenalidomide, induce enhanced T-cell activation and NK-cell activation, it could be a useful track to enhance graft-vs-myeloma effect after allo-SCT. Therefore, we investigated the efficacy of lenalidomide in 24 patients with multiple myeloma who had relapsed after allo-SCT. In eight patients, immunomonitoring of T-cell and NK-cell subpopulations before and after lenalidomide therapy was performed. Patients A total of 24 patients with a median age of 59 years (range: 37–70) were enrolled in this retrospective study. Revlimid was approved for salvage therapy and the study was performed according to institutional guidelines. For monitoring T and NK cells, patients gave written informed consent. A total of 12 patients had received stem cells from a related donor, and 12 patients from an unrelated donor. The median interval between allo-SCT and relapse was 18 months (range: 2–71). The median number of earlier chemotherapy cycles was six (range: 2–13). All patients had received at least one earlier allo-SCT; six patients had received two earlier autografts, and one patient had received three earlier autografts. Del 13q14 cytogenetic abnormalities as confirmed by interphase FISH was positive in 12 out of 18 patients. The median interval between relapse after allo-trans- plantation and start of lenalidomide therapy was 11 months (range: 1–56). Other salvage therapies for relapse after allografting and before lenalidomide were donor lympho- cyte infusion (n ¼ 18), thalidomide-containing regimens (n ¼ 11), bortezomib-containing regimens (n ¼ 13) or earlier radiotherapy (n ¼ 14). Only one patient received lenalido- mide as first-line salvage therapy after failure to allograft. The median number of lenalidomide cycles was five Received 20 February 2009; revised 3 April 2009; accepted 20 May 2009; published online 6 July 2009 Correspondence: Professor N Kro¨ger, Department for Stem Cell Transplantation, University Hospital Hamburg-Eppendorf, Martinis- trasse 52, D-20246 Hamburg, Germany. E-mail: nkroeger@uke.uni-hamburg.de Bone Marrow Transplantation (2010) 45, 349–353 & 2010 Macmillan Publishers Limited All rights reserved 0268-3369/10 $32.00 www.nature.com/bmt