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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

Authors' Affiliations: ¹ Department of Haematology and ² Department of Oncology (Radiumhemmet) and CancerCentreKarolinska, Karolinska University Hospital; ³ Department of Oncology-Pathology, Karolinska Institutet, Stockholm, Sweden

Requests for reprints: Anders Osterborg, Department of Oncology, Karolinska University Hospital Solna, SE-171 76 Stockholm, Sweden. Phone: 46-8-517-755-08; Fax: 46-8-31-83-27; E-mail: anders.osterborg{at}karolinska.se.

Purpose and Experimental Design: 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 [³H]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.

Commentary

Idiotype Vaccination Strategies in Myeloma: How to Overcome a Dysfunctional Immune System

Frits van Rhee
Clin. Cancer Res. 2007 13: 1353-1355. [Full Text] [PDF]

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				A. O. Abdalla, P. Kokhaei, L. Hansson, H. Mellstedt, and A. Osterborg Idiotype vaccination in patients with myeloma reduced circulating myeloma cells (CMC) Ann. Onc., June 1, 2008; 19(6): 1172 - 1179. [Abstract] [Full Text] [PDF]

				F. v. Rhee Idiotype Vaccination Strategies in Myeloma: How to Overcome a Dysfunctional Immune System Clin. Cancer Res., March 1, 2007; 13(5): 1353 - 1355. [Full Text] [PDF]