Idiotype vaccination using dendritic cells after autologous peripheral blood stem cell transplantation for multiple myeloma - A feasibility study

The idiotype (Id) determinant on the multiple myeloma (MM) protein can be r egarded as a tumor-specific marker. Immunotherapy directed at the MM Id may stem the progression of this disease. We report here on the first 12 MM pa tients treated at our institution with high-dose therapy and peripheral blo od stem cell transplantation (PBSCT) followed by Id immunizations. MM patie nts received PBSCT to eradicate the majority of the disease. PBSCT produced a complete response in 2 patients, a partial response in 9 patients and st able disease in 1 patient. Three to 7 months after high-dose therapy, patie nts received a series of monthly immunizations that consisted of two intrav enous infusions of Id-pulsed autologous dendritic cells (DC) followed by fi ve subcutaneous boosts of Id/keyhole limpet hemocyanin (KLH) administered w ith adjuvant. Between 1 and 11 x 10(6) DC were obtained by leukapheresis in all patients even after PBSCT. The administration of Id-pulsed DC and Id/K LH vaccines were well tolerated with patients experiencing only minor and t ransient side effects. Two of 12 patients developed an Id-specific, cellula r proliferative immune response and one of three patients studied developed a transient but Id-specific cytotoxic T-cell (CTL) response. Eleven of the 12 patients generated strong KLH-specific cellular proliferative immune re sponses showing the patients' immunocompetence at the time of vaccination. The two patients who developed a cellular Id-specific immune response remai n in complete remission. Of the 12 treated patients, 9 are currently alive after autologous transplantation with a minimum follow-up of 16 months, 2 p atients died because of recurrent MM and 1 patient succumbed to acute leuke mia. These studies show that patients make strong anti-KLH responses despit e recent high-dose therapy and that DC-based Id vaccination is feasible aft er PBSCT and can induce Id-specific T-cell responses. Further vaccine devel opment is necessary to increase the proportion of patients that make Id-spe cific immune responses, The clinical benefits of Id vaccination in MM remai n to be determined. (C) 1999 by The American Society of Hematology.