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

5 Citations (Scopus)

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

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Stem Cell Transplantation
Immunity
Bispecific Antibodies
T-Lymphocytes
Humoral Immunity
Multiple Myeloma
Bone Marrow
Clinical Trials
Antibodies
Enzymes

Keywords

  • Activated T cells
  • Bispecific antibodies
  • Multiple myeloma

ASJC Scopus subject areas

  • Hematology
  • Transplantation

Cite this

Targeting CD138-/CD20+ Clonogenic Myeloma Precursor Cells Decreases These Cells and Induces Transferable Antimyeloma Immunity. / Lum, Lawrence G.; Thakur, Archana; Kondadasula, Sri Vidya; Al-Kadhimi, Zaid; Deol, Abhinav; Tomaszewski, Elyse N.; Yano, Hiroshi; Schalk, Dana L.; Ayash, Lois; Zonder, Jeffrey A.; Uberti, Joseph P.; Abidi, Muneer H.; Ratanatharathorn, Voravit.

In: Biology of Blood and Marrow Transplantation, Vol. 22, No. 5, 01.05.2016, p. 869-878.

Research output: Contribution to journalArticle

Lum, LG, Thakur, A, Kondadasula, SV, Al-Kadhimi, Z, Deol, A, Tomaszewski, EN, Yano, H, Schalk, DL, Ayash, L, Zonder, JA, Uberti, JP, Abidi, MH & Ratanatharathorn, V 2016, 'Targeting CD138-/CD20+ Clonogenic Myeloma Precursor Cells Decreases These Cells and Induces Transferable Antimyeloma Immunity', Biology of Blood and Marrow Transplantation, vol. 22, no. 5, pp. 869-878. https://doi.org/10.1016/j.bbmt.2015.12.030
Lum, Lawrence G. ; Thakur, Archana ; Kondadasula, Sri Vidya ; Al-Kadhimi, Zaid ; Deol, Abhinav ; Tomaszewski, Elyse N. ; Yano, Hiroshi ; Schalk, Dana L. ; Ayash, Lois ; Zonder, Jeffrey A. ; Uberti, Joseph P. ; Abidi, Muneer H. ; Ratanatharathorn, Voravit. / Targeting CD138-/CD20+ Clonogenic Myeloma Precursor Cells Decreases These Cells and Induces Transferable Antimyeloma Immunity. In: Biology of Blood and Marrow Transplantation. 2016 ; Vol. 22, No. 5. pp. 869-878.
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AU - Lum, Lawrence G.

AU - Thakur, Archana

AU - Kondadasula, Sri Vidya

AU - Al-Kadhimi, Zaid

AU - Deol, Abhinav

AU - Tomaszewski, Elyse N.

AU - Yano, Hiroshi

AU - Schalk, Dana L.

AU - Ayash, Lois

AU - Zonder, Jeffrey A.

AU - Uberti, Joseph P.

AU - Abidi, Muneer H.

AU - Ratanatharathorn, Voravit

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N2 - 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.

AB - 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.

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