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

Lawrence G. Lum, Archana Thakur, Sri Vidya Kondadasula, Zaid Al-Kadhimi, Abhinav Deol, Elyse N. Tomaszewski, Hiroshi Yano, Dana L. Schalk, Lois Ayash, Jeffrey A. Zonder, Joseph P. Uberti, Muneer H. Abidi, Voravit Ratanatharathorn

Research output: Contribution to journalArticle

8 Scopus citations

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 be transferred and boosted after SCT.

Original languageEnglish (US)
Pages (from-to)869-878
Number of pages10
JournalBiology of Blood and Marrow Transplantation
Volume22
Issue number5
DOIs
StatePublished - May 1 2016

Keywords

  • Activated T cells
  • Bispecific antibodies
  • Multiple myeloma

ASJC Scopus subject areas

  • Hematology
  • Transplantation

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    Lum, L. G., Thakur, A., Kondadasula, S. V., Al-Kadhimi, Z., Deol, A., Tomaszewski, E. N., Yano, H., Schalk, D. L., Ayash, L., Zonder, J. A., Uberti, J. P., Abidi, M. H., & Ratanatharathorn, V. (2016). Targeting CD138-/CD20+ Clonogenic Myeloma Precursor Cells Decreases These Cells and Induces Transferable Antimyeloma Immunity. Biology of Blood and Marrow Transplantation, 22(5), 869-878. https://doi.org/10.1016/j.bbmt.2015.12.030