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

•This proof-of-principal study suggests that pretargeting CD138-/CD20+ cells in patients with multiple myeloma (MM) with infusions of bispecific antibody-armed T cells (BATs) before autologous stem cell transplantation (SCT) is safe and does not impair engraftment or immune recovery.•BATs infusions reduced the proportions of clonogenic myeloma precursor cells (CMPCs) in bone marrow and induced cellular and humoral anti-MM immunity.•Both humoral (anti-SOX2 antibody) and cellular (anti-MM IFN-γ ELISPOT) responses could be detected after SCT and boosted by a single BATs infusion.•Anti-SOX2 antibody levels and IFN-γ ELISPOT responses were higher in patients who were in remission compared with those who relapsed.•The presence of anti-SOX2 antibodies may provide an anti-MM effect after SCT.

This phase Ib clinical trial evaluated whether pretargeting of CD20+ clonogenic myeloma precursor cells (CMPCs) with anti-CD3 × anti-CD20 bispecific antibody-armed T cells (BATs) before autologous stem cell transplantation (SCT) in patients with standard-risk and high-risk multiple myeloma would induce antimyeloma immunity that could be detected and boosted after SCT. All 12 patients enrolled in this study received 2 BATs infusions before SCT, and 4 patients received a booster infusion of BATs after SCT. Pretargeting CD138−/CD20+ CMPCs with BATs before SCT 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-γ 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 antimyeloma immunity that could be transferred and boosted after SCT.