Combined Infusion of Anti-CD19 and Anti-Bcma CART Cells after Early or Later Transplantation in the Front Line Was Superior to Salvage Therapy for High Risk MM

作者：Xiaolan Shi, Lingzhi Yan, Jingjing Shang, Liqing Kang, Song Jin, Huizhu Kang, Ruju Wang, Zhu Mingqing, Jiazi Zhou, Feiran Gong, Guanghua Chen, Jin Zhou, Huirong Chang, Weiqin Yao, Ying Yao, Yong Liu, Zhi Yan, Juanjuan Su, Depei Wu, Lei Yu, Fu Cheng Cheng · 发表于：Blood · 年份：2019 · DOI：10.1182/blood-2019-131546 · 被引用次数：17 · 研究领域：CAR-T cell therapy research、Hematopoietic Stem Cell Transplantation、Multiple Myeloma Research and Treatments

Background: Multiple myeloma (MM) is an incurable plasma cell malignancies despite the advent of numerously new drugs especially for high risk patients. Our previous study showed good response for the de novo high risk patients who received CD19 and BCMA-specific CART cell therapy after ASCT in the front line with mild CRS and other side effects (reported on the 2018 ASH meeting). To determine the best time to do ASCT and CART cell treatment for those patients, we retrospectively analyzed the patients' outcome according to their time to do autologous transplantation (NCT 03455972). Methods:The high risk MM patients defined in this study were in R-ISS stage III, IgD/IgE type, or with measurable EMD,or who only achieved PR or less after 4 cycles of triplet induction or relapsed. Lymphocytes were collected from PBSCs and cultured with an anti-CD3 monoclonal antibody to activate T-cell proliferation after stem cell collection. The cells were transduced with recombinant lentiviral verctors which respectively contained the anti-BCMA or anti-CD19 single chain variable fragment (scFv), the cytoplasmic portion of the OX40 and CD28 costimulatory moiety, and the CD3z T-cell activation domain. This is the new third generation CAR technique applied in clinic. BuCy or Melphalan were used as conditioning, followed by infusion of autologous stem cells. CART-19 (1×107/kg on d0) and CART-BCMA cells as split-dose (40% on d1 and 60% on d2) were infused directly on d14 to d20 after transplantatio...