Idiotype vaccination in human myeloma: Generation of tumor-specific immuneresponses after high-dose chemotherapy

Igs contain unique portions, collectively termed idiotypes (Id), that can b e recognized by the immune system. Id expressed by tumor cells in B-cell ma lignancies can be regarded as tumor-specific antigens and a target for vacc ine immunotherapy. We have started a vaccination trial in multiple myeloma (MM) using Id-specific proteins conjugated to keyhole limpet hemocyanin (KL H) as immunogens and low doses of subcutaneous granulocyte-macrophage colon y-stimulating factor (GM-CSF) or interleukin-2 (IL-2) as immunoadjuvants. T welve patients who had previously been treated with high-dose chemotherapy followed by peripheral blood progenitor cell (PBPC) transplantation entered this study from August 1995 to January 1998. All patients were in first re mission at the time of vaccination. They received subcutaneous injections o f Id vaccines and immunoadjuvants in an outpatient setting. The generation of Id-specific T-cell proliferative responses was documented in 2 patients, whereas a positive Id-specific delayed-type hypersensitivity (DTH) reactio n was observed in 8 of the 10 patients studied. DTH specificity was confirm ed in 1 patient by investigating the reactivity to synthetic peptides deriv ed from the VDJ sequence of the tumor-specific Ig heavy chain. None of the patients generated soluble immune responses to Id, whereas the generation o f soluble and cellular immune responses to KLH was observed in 100% and 80% , respectively. Eleven patients completed the treatment, whereas 1 patient failed to finish owing to progression of disease. Freedom from disease prog ression (FFDP), measured from the date of first Id/KLH injection to the dat e of first treatment after vaccination or last follow-up, ranged from 9 to 36 months. These data indicate that the immune competence status of MM pati ents is still susceptible to specific immunization after high-dose chemothe rapy and PBPC transplantation. It remains to be determined whether generati on of Id-specific immune responses can reduce the relapse rate of patients with minimal residual disease. (C) 1999 by The American Society of Hematolo gy.