Idiotype vaccination in patients with myeloma reduced circulating myeloma cells (CMC)

• Published in: Annals of oncology Vol. 19; no. 6; pp. 1172 - 1179
• Main Authors: Abdalla, A.O., Kokhaei, P., Hansson, L., Mellstedt, H., Österborg, A.
• Format: Journal Article
• Language: English
• Published: Oxford Elsevier Ltd 01.06.2008; Oxford University Press; Oxford Publishing Limited (England)
• Subjects: Adjuvants, Immunologic - administration & dosage; Aged; Aged, 80 and over; Antineoplastic agents; Biological and medical sciences; Cancer Vaccines - immunology; Cancer Vaccines - therapeutic use; circulating myeloma cells; Female; Granulocyte-Macrophage Colony-Stimulating Factor - administration & dosage; Hematologic and hematopoietic diseases; Humans; idiotype vaccination; Immunodeficiencies. Immunoglobulinopathies; Immunoglobulin Idiotypes - immunology; Immunoglobulin Idiotypes - therapeutic use; Immunoglobulinopathies; Immunopathology; Interleukin-12 - administration & dosage; Leukemias. Malignant lymphomas. Malignant reticulosis. Myelofibrosis; Male; Medical sciences; Medicin och hälsovetenskap; Middle Aged; multiple myeloma; Multiple Myeloma - drug therapy; Multiple Myeloma - immunology; Neoplastic Cells, Circulating - drug effects; Pharmacology. Drug treatments; Vaccination; circulating myeloma cells; idiotype vaccination; multiple myeloma; Human; Immunopathology; Vaccination; B cell neoplasm; Malignant hemopathy; Lymphoid neoplasm; Myeloma; In vitro; Prevention; Immunoglobulinopathy; Lymphoproliferative syndrome; Cancer; Idiotype
• ISSN: 0923-7534; 1569-8041; 1569-8041
• DOI: 10.1093/annonc/mdn017

Circulating myeloma cells (CMC), exhibiting the same immunoglobulin heavy-chain gene rearrangements as the plasma cells, are part of the myeloma clone. In this study, we evaluated the effect of idiotype (Id) vaccination on CMC. Eleven patients were immunized with the autologous Id in combinations with granulocyte–macrophage colony-stimulating factor and interleukin 12, and followed for CMC by quantitative real-time allele-specific PCR. Id-specific T cells were monitored by proliferation assay, enzyme-linked immunospot (interferon-γ) assay, and quantitative real-time PCR for cytokines. Regulatory T (Treg) cells were analyzed by flow cytometry. CMC were detected in 9 of 11 patients at start of vaccination. In four patients, CMC declined and two had a complete molecular remission. Further two patients had stable levels of CMC during follow-up, while in three patients CMC progressively increased. Six patients had a vaccine-induced Id-specific T-cell response. A significant correlation was observed between reduced/stable levels of CMC and the Id-specific T cells (P < 0.02). The frequency of Treg cells was decreased in immune responders, but increased in immune nonresponders (P < 0.05). No significant change in the serum M-protein concentration was, however, observed in any patient. Id vaccination reduced CMC, which correlated with vaccine-induced Id-specific T cells. Further studies are warranted to analyze the clinical significance of CMC and clinical effects of Id vaccination.