Targeting CD138-/CD20+Clonogenic Myeloma Precursor Cells Decreases These Cells and Induces Transferable Antimyeloma Immunity

This phase lb clinical trial evaluated whether pretargeting of CD20(+) clonogenic myeloma precursor cells (CMPCs) with anti-CD3 x anti-CD20 bispecific antibody-armed T cells (BATs) before autologous stem cell transplantation (SO') in patients with standard-risk and high-risk multiple myeloma would induce anti-myeloma immunity that could be detected and boosted after SO'. All 12 patients enrolled in this study received 2 BATs infusions before SO', and 4 patients received a booster infusion of BATs after SCT. Pretargeting CD138(-)/CD20(+) CMPCs with BATs before SO' was safe and reduced levels of CMPCs by up to 58% in the postinfusion bone marrow in patients who remained in remission. Four of 5 patients who remained in remission had a >5-fold increase in IFN-gamma enzyme-linked immunospot responses. SOX2 antibody increased after BATs infusions and persisted after SCT. The median anti-SOX2 level at 3 months after SCT was 28.1 ng/mL (range, 4.6 to 256 ng/mL) in patients who relapsed and 46 ng/mL (range, 28.3 to 73.3 ng/mL) in patients who remained in remission. The immune correlates suggest that infusions of targeted T cells given before SCT were able to reduce CMPC levels and induced cellular and humoral anti-myeloma immunity that could be transferred and boosted after SCT. (C) 2016 American Society for Blood and Marrow Transplantation.