Long-term idiotype vaccination combined with interleukin-12 (IL-12), or IL-12 and granulocyte macrophage colony-stimulating factor, in early-stage multiple myeloma patients.
OBJECTIVE
Twenty-eight patients with immunoglobulin G myeloma stages I to II were immunized i.d. over 110 weeks with autologous M protein combined with interleukin-12 (IL-12; n = 15) or with IL-12 and granulocyte macrophage colony-stimulating factor (GM-CSF; n = 13). Idiotype-specific T-cell responses were assessed by [(3)H]thymidine incorporation, enzyme-linked immunospot assay, and delayed-type hypersensitivity reaction.


RESULTS
Based on these three assays, idiotype-specific immune responses were noted in 5 of 15 (33%) patients in the IL-12 group and in 11 of 13 (85%) patients in the GM-CSF/IL-12 group (P < 0.01). Immune response was seen only in patients with M-component concentration of <50 g/L. Three of 16 (19%) responders showed a gradually increasing idiotype-specific T-cell response, whereas 11 of 16 (69%) patients showed initial response, which then disappeared rapidly; the latter pattern was frequently associated with subsequent progressive disease. Immune nonresponse was associated with an increase in the numbers of CD4(+)/CD25(+) cells (regulatory T cells), which was absent in responding patients. Median time to progression for immune responders (n = 16) was 108 weeks compared with 26 weeks for nonresponders (n = 12; P = 0.03).


CONCLUSIONS
These results indicate that idiotype immunization of myeloma patients with GM-CSF and IL-12 may induce specific T-cell response more frequently than with IL-12 alone and that immune response may correlate with time to progression and nonresponse with increased numbers of regulatory T cells.
Hansson
Lotta
L
Department of Haematology, CancerCentre Karolinska, Karolinska University Hospital, Stockholm, Sweden.
Abdalla
Amir Osman
AO
Moshfegh
Ali
A
Choudhury
Aniruddha
A
Rabbani
Hodjattallah
H
Nilsson
Bo
B
Osterborg
Anders
A
Mellstedt
Håkan
H
D000276:Adjuvants, Immunologic / Q000627:therapeutic use*; D000368:Aged; D019496:Cancer Vaccines / Q000276:immunology / Q000627:therapeutic use*; D004797:Enzyme-Linked Immunosorbent Assay; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000276:immunology / Q000627:therapeutic use; D006801:Humans; D007130:Immunoglobulin Idiotypes / Q000276:immunology / Q000627:therapeutic use*; D007167:Immunotherapy / Q000379:methods*; D018664:Interleukin-12 / Q000276:immunology / Q000627:therapeutic use; D008875:Middle Aged; D009101:Multiple Myeloma / Q000188:drug therapy* / Q000276:immunology; D009194:Myeloma Proteins / Q000276:immunology; D050378:T-Lymphocytes, Regulatory / Q000276:immunology; D013997:Time Factors
D000276:Adjuvants, Immunologic; D019496:Cancer Vaccines; D007130:Immunoglobulin Idiotypes; D009194:Myeloma Proteins; C085016:multiple myeloma M-proteins; D018664:Interleukin-12; D016178:Granulocyte-Macrophage Colony-Stimulating Factor