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Targeting CD138-/CD20+ Clonogenic Myeloma Precursor Cells Decreases These Cells and Induces Transferable Antimyeloma
Lawrence G Lum1, Archana Thakur2, Sri Vidya Kondadasula2
1Department of Oncology, Wayne State University, Detroit, Michigan; Department of Medicine, Wayne State University, Detroit, Michigan; Department of Immunology and Microbiology, Wayne State University, Detroit, Michigan.
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.
Insights
This trial investigated bispecific antibody-armed T cells (BATs) for multiple myeloma before stem cell transplant (SCT). BATs were safe, reduced myeloma precursor cells, and induced lasting anti-myeloma immunity post-SCT.
Area of Science:
- Immunology
- Oncology
- Cellular Therapy
Background:
- Multiple myeloma is a cancer of plasma cells.
- Current treatments like autologous stem cell transplantation (SCT) can be improved with enhanced immune responses.
- Targeting clonogenic myeloma precursor cells (CMPCs) is a strategy to prevent relapse.
Purpose of the Study:
- To evaluate the safety and efficacy of pretargeting CD20(+) CMPCs with bispecific antibody-armed T cells (BATs) before SCT.
- To assess if BATs induce detectable and boostable anti-myeloma immunity after SCT.
- To explore immune correlates of response in patients with multiple myeloma.
Main Methods:
- Phase Ib clinical trial involving 12 patients with standard-risk and high-risk multiple myeloma.
- Patients received 2 infusions of BATs before SCT; 4 received a booster infusion post-SCT.
- Evaluated reduction in CMPCs, IFN-γ enzyme-linked immunospot responses, and anti-SOX2 antibody levels.
Main Results:
- Pretargeting CMPCs with BATs before SCT was safe.
- Reduced CMPC levels by up to 58% in patients in remission.
- Induced cellular and humoral anti-myeloma immunity, with detectable and boostable responses post-SCT.
Conclusions:
- Pretargeting CMPCs with BATs before SCT is a safe and feasible approach.
- BATs can reduce CMPC burden and induce sustained anti-myeloma immune responses.
- This strategy holds promise for improving outcomes in multiple myeloma patients undergoing SCT.
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