title: Epigenetic induction of adaptive immune response in multiple myeloma: sequential azacitidine and lenalidomide generate cancer testis antigen-specific cellular immunity.
abstract: Patients with multiple myeloma (MM) undergoing high dose therapy and autologous stem cell transplantation (SCT) remain at risk for disease progression. Induction of the expression of highly immunogenic cancer testis antigens (CTA) in malignant plasma cells in MM patients may trigger a protective immune response following SCT. We initiated a phase II clinical trial of the DNA hypomethylating agent, azacitidine (Aza) administered sequentially with lenalidomide (Rev) in patients with MM. Three cycles of Aza and Rev were administered and autologous lymphocytes were collected following the 2nd and 3rd cycles of Aza-Rev and cryopreserved. Subsequent stem cell mobilization was followed by high-dose melphalan and SCT. Autologous lymphocyte infusion (ALI) was performed in the second month following transplantation. Fourteen patients have completed the investigational therapy; autologous lymphocytes were collected from all of the patients. Thirteen patients have successfully completed SCT and 11 have undergone ALI. Six patients tested have demonstrated CTA up-regulation in either unfractionated bone marrow (n = 4) or CD138+ cells (n = 2). CTA (CTAG1B)-specific T cell response has been observed in all three patients tested and persists following SCT. Epigenetic induction of an adaptive immune response to cancer testis antigens is safe and feasible in MM patients undergoing SCT.
authors: Bone Marrow Transplant Program, Department of Internal Medicine, Massey Cancer Center, Virginia Commonwealth University, Richmond, VA 23298, USA. atoor@vcu.edu
authors: Amir A
authors: AA
authors: Toor
authors: Kyle K
authors: KK
authors: Payne
authors: Harold M
authors: HM
authors: Chung
authors: Roy T
authors: RT
authors: Sabo
authors: Allison F
authors: AF
authors: Hazlett
authors: Maciej
authors: M
authors: Kmieciak
authors: Kimberly
authors: K
authors: Sanford
authors: David C
authors: DC
authors: Williams
authors: William B
authors: WB
authors: Clark
authors: Catherine H
authors: CH
authors: Roberts
authors: John M
authors: JM
authors: McCarty
authors: Masoud H
authors: MH
authors: Manjili
mesh_terms: D000328:Adult; D000368:Aged; D000951:Antigens, Neoplasm / Q000276:immunology*; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage / Q000627:therapeutic use*; D001374:Azacitidine / Q000008:administration & dosage / Q000494:pharmacology*; D001897:Boronic Acids / Q000008:administration & dosage; D000069286:Bortezomib; D019175:DNA Methylation / Q000187:drug effects*; D003907:Dexamethasone / Q000008:administration & dosage; D004317:Doxorubicin / Q000008:administration & dosage; D004334:Drug Administration Schedule; D044127:Epigenesis, Genetic / Q000187:drug effects*; D005260:Female; D006801:Humans; D007111:Immunity, Cellular / Q000187:drug effects*; D000077269:Lenalidomide; D017710:Lymphocyte Transfusion; D008297:Male; D008875:Middle Aged; D009101:Multiple Myeloma / Q000188:drug therapy / Q000276:immunology* / Q000601:surgery; D036102:Peripheral Blood Stem Cell Transplantation; D010950:Plasma Cells / Q000276:immunology; D011446:Prospective Studies; D011719:Pyrazines / Q000008:administration & dosage; D037182:T-Cell Antigen Receptor Specificity / Q000187:drug effects*; D013792:Thalidomide / Q000008:administration & dosage / Q000031:analogs & derivatives; D014182:Transplantation, Autologous
chemical_list: D000951:Antigens, Neoplasm; D001897:Boronic Acids; D011719:Pyrazines; C542434:cancer testis antigen NXF2, human; D013792:Thalidomide; D000069286:Bortezomib; D003907:Dexamethasone; D004317:Doxorubicin; D000077269:Lenalidomide; D001374:Azacitidine