Lenalidomide consolidation and maintenance therapy after autologous stem cell transplant for multiple myeloma induces persistent changes in T-cell homeostasis.
Whether the efficacy of lenalidomide in the treatment of multiple myeloma (MM) is due to direct tumor toxicity only or to additional immunomodulatory effects is unclear. We studied the effect of lenalidomide treatment on T-cell immune reconstitution in patients with MM who had undergone autologous peripheral blood stem cell transplant (ASCT). Twenty-nine newly diagnosed patients with MM received induction therapy followed by high-dose melphalan and ASCT. After ASCT, 11 patients received lenalidomide consolidation therapy for 2 months followed by maintenance therapy until disease progression. The remaining 18 patients received no treatment. Serial analysis of thymic output, as given by numbers of T-cell receptor excision circles (sjTRECs), and T-cell phenotyping was performed until 18 months post-ASCT. Lenalidomide impaired long-term thymic T-cell reconstitution, decreased CD4 + and CD8 + CD45RA + CCR7 - effector-terminal T-cell absolute counts and increased CD4 + CD25 + CD127 - /low regulatory T-cells. Lenalidomide consolidation and long-term maintenance therapy, administered post-ASCT, may have a potentially negative impact on immune surveillance.
INSERM UMRS 940, AP-HP, Hôpital Saint Louis, Département d'immunologie, Université Paris Diderot-Paris 7 , Paris , France.
Emmanuel
E
Clave
Corinne
C
Douay
Tereza
T
Coman
Marc
M
Busson
Caroline
C
Bompoint
Helene
H
Moins-Teisserenc
Salomé
S
Glauzy
Maryvonnick
M
Carmagnat
Norbert Claude
NC
Gorin
Antoine
A
Toubert
Laurent
L
Garderet
D000328:Adult; D000954:Antigens, Surface / Q000378:metabolism; D000970:Antineoplastic Agents / Q000494:pharmacology / Q000627:therapeutic use*; D016022:Case-Control Studies; D060830:Consolidation Chemotherapy; D018380:Hematopoietic Stem Cell Transplantation; D006706:Homeostasis / Q000187:drug effects / Q000276:immunology*; D006801:Humans; D016130:Immunophenotyping; D000077269:Lenalidomide; D060046:Maintenance Chemotherapy; D008875:Middle Aged; D009101:Multiple Myeloma / Q000175:diagnosis / Q000276:immunology* / Q000401:mortality / Q000628:therapy*; D009367:Neoplasm Staging; D016176:T-Lymphocyte Subsets / Q000187:drug effects / Q000276:immunology*; D050378:T-Lymphocytes, Regulatory / Q000187:drug effects / Q000378:metabolism; D013792:Thalidomide / Q000031:analogs & derivatives* / Q000494:pharmacology / Q000627:therapeutic use; D013950:Thymus Gland / Q000276:immunology; D014182:Transplantation, Autologous; D016896:Treatment Outcome
D000954:Antigens, Surface; D000970:Antineoplastic Agents; D013792:Thalidomide; D000077269:Lenalidomide
Multiple myeloma; T-cell homeostasis; autologous stem cell transplant; lenalidomide