title: Lenalidomide maintenance after nonmyeloablative allogeneic stem cell transplantation in multiple myeloma is not feasible: results of the HOVON 76 Trial.
abstract: To improve the outcome of allogeneic stem cell transplantation (allo-SCT) in multiple myeloma as part of first-line treatment, we prospectively investigated the feasibility and efficacy of lenalidomide maintenance. Patients started maintenance 1 to 6 months after nonmyeloablative allo-SCT. Lenalidomide was dosed 10 mg on days 1 to 21 of a 28-day schedule for a total of 24 cycles. Peripheral blood samples were taken to evaluate immune modulating effects. Thirty-five eligible patients were enrolled, and 30 started with lenalidomide. After 2 cycles, 14 patients (47%) had to stop treatment, mainly because of the development of acute graft versus host disease (GVHD). In total, 13 patients (43%) stopped treatment because of development of GVHD, 5 patients (17%) because of other adverse events, and 5 patients (17%) because of progression. Responses improved in 37% of patients, and the estimated 1-year progression-free survival from start of maintenance was 69% (90% confidence interval, 53%-81%). Lenalidomide increased the frequency of human leukocyte antigen-DR(+) T cells and regulatory T cells, without correlation with clinical parameters. In conclusion, lenalidomide maintenance 10 mg daily after nonmyeloablative allo-SCT with unmanipulated graft in multiple myeloma patients is not feasible, mainly because of the induction of acute GVHD. This trial was registered at www.trialregister.nl as #NTR1645.
authors.affiliation: Department of Hematology, University Medical Center Utrecht, Utrecht, The Netherlands.
authors.forename: Evelien
authors.initials: E
authors.lastname: Kneppers
authors.forename: Bronno
authors.initials: B
authors.lastname: van der Holt
authors.forename: Marie-Jose
authors.initials: MJ
authors.lastname: Kersten
authors.forename: Sonja
authors.initials: S
authors.lastname: Zweegman
authors.forename: Ellen
authors.initials: E
authors.lastname: Meijer
authors.forename: Gerwin
authors.initials: G
authors.lastname: Huls
authors.forename: Jan J
authors.initials: JJ
authors.lastname: Cornelissen
authors.forename: Jeroen J
authors.initials: JJ
authors.lastname: Janssen
authors.forename: Cynthia
authors.initials: C
authors.lastname: Huisman
authors.forename: Petra B
authors.initials: PB
authors.lastname: Cornelisse
authors.forename: Cheryl P
authors.initials: CP
authors.lastname: Bruijnen
authors.forename: Maarten
authors.initials: M
authors.lastname: Emmelot
authors.forename: Pieter
authors.initials: P
authors.lastname: Sonneveld
authors.forename: Henk M
authors.initials: HM
authors.lastname: Lokhorst
authors.forename: Tuna
authors.initials: T
authors.lastname: Mutis
authors.forename: Monique C
authors.initials: MC
authors.lastname: Minnema
mesh_terms: D000208:Acute Disease; D000328:Adult; D000368:Aged; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000009:adverse effects* / Q000627:therapeutic use; D003131:Combined Modality Therapy; D003520:Cyclophosphamide / Q000008:administration & dosage / Q000627:therapeutic use; D016572:Cyclosporine / Q000008:administration & dosage / Q000627:therapeutic use; D018572:Disease-Free Survival; D003875:Drug Eruptions / Q000209:etiology; D005240:Feasibility Studies; D005260:Female; D006086:Graft vs Host Disease / Q000453:epidemiology / Q000209:etiology*; D006402:Hematologic Diseases / Q000139:chemically induced; D019650:Hematopoietic Stem Cell Mobilization; D018380:Hematopoietic Stem Cell Transplantation / Q000379:methods*; D006801:Humans; D007155:Immunologic Factors / Q000008:administration & dosage / Q000009:adverse effects* / Q000627:therapeutic use; D007166:Immunosuppressive Agents / Q000008:administration & dosage / Q000627:therapeutic use; D000077269:Lenalidomide; D018655:Lymphocyte Count; D008297:Male; D008558:Melphalan / Q000008:administration & dosage / Q000627:therapeutic use; D008875:Middle Aged; D009101:Multiple Myeloma / Q000188:drug therapy* / Q000601:surgery; D009173:Mycophenolic Acid / Q000008:administration & dosage / Q000031:analogs & derivatives / Q000627:therapeutic use; D011446:Prospective Studies; D012074:Remission Induction; D013792:Thalidomide / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000627:therapeutic use; D019172:Transplantation Conditioning / Q000379:methods; D014182:Transplantation, Autologous; D014184:Transplantation, Homologous; D014916:Whole-Body Irradiation
chemical_list: D000970:Antineoplastic Agents; D007155:Immunologic Factors; D007166:Immunosuppressive Agents; D013792:Thalidomide; D016572:Cyclosporine; D003520:Cyclophosphamide; D000077269:Lenalidomide; D009173:Mycophenolic Acid; D008558:Melphalan