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.