Sibling donor immunization with patient-derived Id-KLH vaccine prior to reduced-intensity allogeneic hematopoietic cell transplantation for multiple myeloma

Abstract

7024 Background: Relapse is the most common cause of treatment failure after reduced-intensity allogeneic hematopoietic cell transplantation (RI-alloHCT) for multiple myeloma (MM). To enhance graft-versus-myeloma effects, we investigated the use of patient-specific idiotype (Id) vaccine in both donors and recipients. Methods: Id protein was obtained by plasmapheresis and conjugated to keyhole limpet hemocyanin (Id-KLH) to generate vaccine. Donors received 3 SQ injections of Id-KLH + GM-CSF at 10, 8, and 4 weeks before stem cell donation. MM pts received a reduced-intensity conditioning regimen (Flu/Cy) and GVHD prophylaxis consisted of cyclosporine plus methotrexate. MM pts were vaccinated with the Id-KLH+GM-CSF at 3, 4, and 6 months post-transplant. Humoral responses were determined by ELISA and Th1 (IL-2, IFN-γ, TNF-α, and GM-CSF) and Th2 (IL-4, IL-5, IL-10, and IL-13) cellular immune responses against Id and KLH were determined by multiplex cytokine assay. Results: Ten MM pts (median age: 54 years; IgG = 8, IgA = 2) and their respective donors were enrolled onto study. All 10 donors completed vaccinations without significant complications. Following vaccination, KLH-specific antibody and Th1/Th2 responses were noted in all 10 donors. Id-specific antibody responses were noted in 6 donors; Th1 and Th2 responses were noted in 5 and 6 donors, respectively. All 10 MM pts underwent RI-alloHCT; the median potential follow-up post-transplant is 43.8 months. Id-specific Th1 and Th2 responses were noted in 5 and 3 pts, respectively, prior to post-transplant immunization; antibody response was noted in 1 patient. Nine evaluable MM pts completed their post-transplant vaccinations. KLH-specific antibody and Th1/Th2 responses were detectable in all 9 pts post-transplant. Id and KLH immune responses were further enhanced by post-transplant vaccinations. Median progression-free survival is 27.3 months; median survival has not been reached. Conclusions: The data suggest Id-specific immunity can be safely induced in normal stem cell donors and passively transferred to recipients of RI-alloHCT. Donor vaccination with tumor-specific antigen represents a tactic to potentially reduce relapse after RI-alloHCT. No significant financial relationships to disclose.