Long-term follow-up of idiotype vaccination in human myeloma as a maintenance therapy after high-dose chemotherapy.
The aim of this work was to evaluate the long-term immunological and clinical impact of idiotype (Id) vaccination in multiple myeloma (MM) patients in first remission after high-dose chemotherapy. A total of 15 patients received a series of subcutaneous (s.c.) injections of autologous Id, conjugated to keyhole limpet hemocyanin (KLH) and in association with low doses of GM-CSF. The median duration of follow-up was 110 months from diagnosis. The vaccine induced immune responses that lasted almost 2 years after the end of treatment. Antibody responses included anti-KLH IgM and IgG (90% of patients), anti-KLH IgE (30%), anti-GM-CSF IgG (20%), anti-Id IgG (20%), and anti-Id IgE (30%). Id-specific delayed type hypersensitivity skin tests were positive in 85% of tested patients. Following vaccination, a progressive recovery of T-cell receptor (TCR) diversity was observed and the loss of oligoclonality was significantly correlated with the remission duration. Although Id/KLH conjugates did not eliminate the residual tumor burden, the median progression-free survival, and overall survival were 40 and 82 months, respectively. A retrospective case-matched analysis showed similar results in patients treated with IFN-alpha alone or in association with steroids. This vaccine formulation can overcome Id-specific immune tolerance by inducing clinical responses that are worthy of further investigation.
Centro di Ricerca in Medicina Sperimentale, Ospedale San Giovanni Battista, Torino, Italy.
M
M
Coscia
S
S
Mariani
S
S
Battaglio
C
C
Di Bello
F
F
Fiore
M
M
Foglietta
A
A
Pileri
M
M
Boccadoro
M
M
Massaia
D000276:Adjuvants, Immunologic / Q000008:administration & dosage; D000888:Antibodies, Anti-Idiotypic / Q000276:immunology / Q000378:metabolism; D000912:Antibodies, Neoplasm / Q000276:immunology / Q000378:metabolism; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage*; D016022:Case-Control Studies; D003131:Combined Modality Therapy; D005500:Follow-Up Studies; D005938:Glucocorticoids / Q000008:administration & dosage; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000008:administration & dosage; D018380:Hematopoietic Stem Cell Transplantation; D006433:Hemocyanins / Q000008:administration & dosage; D006801:Humans; D006968:Hypersensitivity, Delayed / Q000276:immunology; D007111:Immunity, Cellular; D007130:Immunoglobulin Idiotypes / Q000276:immunology / Q000627:therapeutic use*; D007279:Injections, Subcutaneous; D016898:Interferon-alpha / Q000008:administration & dosage; D008875:Middle Aged; D009101:Multiple Myeloma / Q000276:immunology / Q000517:prevention & control* / Q000628:therapy; D009367:Neoplasm Staging; D011948:Receptors, Antigen, T-Cell / Q000378:metabolism; D012074:Remission Induction; D012189:Retrospective Studies; D015996:Survival Rate; D016896:Treatment Outcome; D014611:Vaccination
D000276:Adjuvants, Immunologic; D000888:Antibodies, Anti-Idiotypic; D000912:Antibodies, Neoplasm; D005938:Glucocorticoids; D007130:Immunoglobulin Idiotypes; D016898:Interferon-alpha; D011948:Receptors, Antigen, T-Cell; D016178:Granulocyte-Macrophage Colony-Stimulating Factor; D006433:Hemocyanins; C032808:keyhole-limpet hemocyanin