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T-cell Receptor Therapy Achieves Encouraging Clinical Responses in Multiple Myeloma

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Key Points

  • Researchers modified T cells to attack cancer cells expressing NY-ESO-1, an antigen found in nearly 60% of multiple myelomas and previously shown to be associated with tumor growth and poor prognosis.
  • Nearly 70% of participants had a near complete or complete response within 3 months post treatment, which compares favorably with the expected responses (less than 40%) in patients without high-risk disease following an autologous stem cell transplant.
  • With a median follow-up of 30.1 months, the median progression-free survival was 19.1 months, and the median overall survival had increased to 32.1 months.

Results from a clinical trial investigating a new T-cell receptor therapy demonstrated a clinical response in 80% of patients with multiple myeloma who had advanced disease after undergoing autologous stem cell transplants. Researchers at Penn’s Abramson Cancer Center modified T cells to attack cancer cells expressing NY-ESO-1, an antigen found in nearly 60% of multiple myelomas previously shown to be associated with tumor growth and poor prognosis. The results of the study were published by Rapoport et al in Nature Medicine.

Study Details

In the phase I/II clinical trial of 20 patients, the engineered cells were deemed safe, trafficked to the site of the tumor (bone marrow), and persisted in 90% of the patients who reached 2-year follow-up after infusion, the research team found. Significant antitumor activity was observed as well; nearly 70% had a near-complete or complete response within 3 months post treatment, which compares favorably with the expected responses (less than 40%) in patients without high-risk disease following an autologous stem cell transplant.

This is the first published report of lentiviral vector mediated T-cell receptor therapy that has shown persistence beyond 1 month, said Carl June, MD, Richard W. Vague Professor in Immunotherapy in the Department of Pathology and Laboratory Medicine and Director of Translational Research in the Abramson Cancer Center and the University of Maryland School of Medicine. “This study shows us that these T-cell receptor therapy–specific T cells are safe and feasible in patients expressing NY-ESO-1,” he said. “But it also revealed encouraging antitumor activity and showed impressive durable T-cell persistence.”

For the study, patients received an average of 2.4 billion NY-ESO–engineered CD3 T cells 2 days after an autologous stem cell transplant. The investigational treatment begins by removing patients’ T cells via an apheresis process similar to blood donation and then genetically reprograms them using a cell production process originally developed by Penn's Clinical Cell and Vaccine Production Facility. After being infused back into patients’ bodies, these newly built cells multiply, as well as seek out a peptide expressed by the antigens NY-ESO-1 and LAGE-1 found in multiple myeloma cancer cells.

Study Results

With a median follow-up of 21.1 months, 15 of the 20 patients were alive, and 10 remained progression-free, the researchers report.

Fourteen patients had near-complete responses, two had very good partial responses, two had partial responses, one had stable disease, and one had progressive disease. As of April 2015, with a median follow-up of 30.1 months, the median progression-free survival was 19.1 months, and the median overall survival had increased to 32.1 months.

None of the patients experienced macrophage activate syndrome or cytokine release syndrome, an infusion reaction observed in other gene therapy trials characterized by fever, nausea, chills, hypotension, or rash. There were no treatment-related fatalities.

Relapse was associated with a loss of gene-modified T cells, the authors reported, which suggests that methods for sustaining long-term persistence of engineered T cells in more patients may improve outcomes.

“This is an important step in immunotherapy research for multiple myeloma, a tough-to-beat cancer that is largely incurable, with a 5-year survival rate of approximately 50%, highlighting the need for new approaches to improve therapeutic options including after an autologous stem cell transplant,” said Edward Stadtmauer, MD, Professor of Medicine and Section Chief of Hematologic Malignancies in the Abramson Cancer Cener and co-lead author. “I look forward to building upon this encouraging data and continuing to add to the growing body of research showing the promise of precision immunotherapies for blood cancers and more.”

Dr. June is the corresponding author of the Nature Medicine article and Director of Translational Research at Adaptimmune Therapeutics, the sponsor of this study.

This work was supported by the National Institutes of Health and a Senior Investigator Award for the Multiple Myeloma Research Foundation.

The content in this post has not been reviewed by the American Society of Clinical Oncology, Inc. (ASCO®) and does not necessarily reflect the ideas and opinions of ASCO®.


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