A phase I clinical study of autologous dendritic cell therapy in patients with relapsed or refractory multiple myeloma

Abstract

// Sung-Hoon Jung 1,2 , Hyun-Ju Lee 2 , Youn-Kyung Lee 3 , Deok-Hwan Yang 1 , Hyeoung-Joon Kim 1 , Joon Haeng Rhee 3,4 , Frank Emmrich 5 and Je-Jung Lee 1,2,3 1 Department of Hematology-Oncology, Chonnam National University Hwasun Hospital, Hwasun, Jeollanamdo, Republic of Korea 2 Research Center for Cancer Immunotherapy, Chonnam National University Hwasun Hospital, Hwasun, Jeollanamdo, Republic of Korea 3 Research Institute, Vaxcell-Bio Therapeutics, Hwasun, Jeollanamdo, Republic of Korea 4 Department of Microbiology, Chonnam National University Medical School, Gwangju, Republic of Korea 5 Fraunhofer Institute for Cell Therapy and Immunology, Leipzig, Germany Correspondence to: Je-Jung Lee, email: // Keywords : dendritic cell, VAX-DC/MM, immunotherapy, multiple myeloma Received : June 03, 2016 Accepted : January 03, 2017 Published : January 10, 2017 Abstract Cellular immunotherapy is emerging as a potential immunotherapeutic modality in multiple myeloma (MM). We have developed potent immunotherapeutic agent (VAX-DC/MM) generated by dendritic cells (DCs) loaded with autologous myeloma cells irradiated with ultraviolet B. In this study, we evaluated the safety and efficacy of VAX-DC/MM in patients with relapsed or refractory MM. This trial enrolled relapsed or refractory MM patients who had received both thalidomide- and bortezomib-based therapies. Patients received the intradermal VAX-DC/MM injection every week for 4 weeks. Patients were treated with 5 × 10 6 or 10 × 10 6 cells, with nine patients treated at a higher dose. The median time from diagnosis to VAX-DC/MM therapy was 56.6 months (range, 28.5–130.5). Patients had received a median of five prior treatments, and 75% had received autologous stem cell transplantation. VAX-DC therapy was well-tolerated, and the most frequent adverse events were local reactions at the injection site and infusion-related reactions. In seven of nine patients who received 10×10 6 cells, an immunological response (77.8%) was observed by interferon-gamma ELISPOT assay or a mixed lymphocyte reaction assay for T-cell proliferation. The clinical benefit rate was 66.7% including one (11.1%) with minor response and five (55.6%) with stable disease; three (33.3%) patients showed disease progression. In conclusion, VAX-DC/MM therapy was well-tolerated, and had disease-stabilizing activity in heavily pretreated MM cases. Further studies are needed to increase the efficacy of VAX-DC/MM in patients with MM.