title: Lenalidomide-induced immunomodulation in multiple myeloma: impact on vaccines and antitumor responses.
abstract: OBJECTIVE
  To show that the immunomodulatory drug lenalidomide can be used in patients with relapsed multiple myeloma to augment vaccine responses.
  
  
  METHODS
  Early phase clinical trial of patients with multiple myeloma who received at least one prior therapy. Patients were treated with single-agent lenalidomide and randomized to receive two vaccinations with pneumococcal 7-valent conjugate vaccine (PCV) on different schedules. Cohort A received the first PCV vaccination prior to the initiation of lenalidomide and the second vaccination while on lenalidomide. Cohort B received both vaccinations while on lenalidomide.
  
  
  RESULTS
  PCV-specific humoral and cellular responses were greater in cohort B than A and were more pronounced in the bone marrow than the blood, suggesting that maximal vaccine efficacy was achieved when both vaccines were administered concomitantly with lenalidomide. Patients with a clinical myeloma response showed evidence of a tumor-specific immune response with increases in myeloma-specific IFN-γ(+) T cells and reductions in Th-17 cells.
  
  
  CONCLUSIONS
  This is the first clinical evidence showing that lenalidomide augments vaccine responses and endogenous antitumor immunity in patients and as such may serve as an adjuvant for cancer and possibly infectious vaccines.
authors.affiliation: Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins, Johns Hopkins Medicine, Baltimore, Maryland 21231, USA.
authors.forename: Kimberly
authors.initials: K
authors.lastname: Noonan
authors.forename: Lakshmi
authors.initials: L
authors.lastname: Rudraraju
authors.forename: Anna
authors.initials: A
authors.lastname: Ferguson
authors.forename: Amy
authors.initials: A
authors.lastname: Emerling
authors.forename: Marcela F
authors.initials: MF
authors.lastname: Pasetti
authors.forename: Carol A
authors.initials: CA
authors.lastname: Huff
authors.forename: Ivan
authors.initials: I
authors.lastname: Borrello
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000970:Antineoplastic Agents / Q000494:pharmacology / Q000627:therapeutic use*; D019496:Cancer Vaccines / Q000276:immunology; D015331:Cohort Studies; D005260:Female; D006801:Humans; D056747:Immunomodulation / Q000187:drug effects*; D000077269:Lenalidomide; D008297:Male; D008875:Middle Aged; D009101:Multiple Myeloma / Q000188:drug therapy* / Q000276:immunology*; D022242:Pneumococcal Vaccines / Q000276:immunology; D013601:T-Lymphocytes / Q000276:immunology; D013792:Thalidomide / Q000031:analogs & derivatives* / Q000494:pharmacology / Q000627:therapeutic use; D018074:Vaccines, Conjugate / Q000276:immunology
chemical_list: D000970:Antineoplastic Agents; D019496:Cancer Vaccines; D022242:Pneumococcal Vaccines; D018074:Vaccines, Conjugate; D013792:Thalidomide; D000077269:Lenalidomide