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

Biology of Blood and Marrow Transplantation : Journal of the American Society for Blood and Marrow Transplantation
Lawrence G LumVoravit Ratanatharathorn

Abstract

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 ...Continue Reading

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Citations

May 14, 2019·Expert Opinion on Biological Therapy·Laahn H Foster, Lawrence G Lum
Nov 10, 2017·Blood·Mireya Paulina VelasquezStephen Gottschalk
Dec 4, 2019·BMJ Case Reports·Audi Francesca Setiadi, Yuri Sheikine
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Jan 21, 2021·British Journal of Cancer·Ajit SinghIqbal S Grewal
Mar 12, 2021·Cancer Immunology, Immunotherapy : CII·Alejandra LeivasJoaquín Martínez-López

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