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AACR 2015: New T Cell–Based Immunotherapy Shows Promise for Lethal Stem Cell Transplant Complication

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Key Points

  • In the absence of effective therapy, patients with Epstein-Barr virus–associated lymphoproliferative disorder (EBV-LPD) have an average survival time of only 16 to 56 days.
  • EBV-specific cytotoxic T lymphocyte (EBV-CTL) produced high, durable response rates in patients with rituximab-refractory EBV-LPD.
  • Responses became clinically evident only after T cells expanded in vivo (7–14 days).

More than 60% of patients with Epstein-Barr virus–associated lymphoproliferative disorder (EBV-LPD) that was nonresponsive to standard rituximab (Rituxan) treatment responded to a new type of immunotherapy called Epstein-Barr virus–specific cytotoxic T-lymphocyte (EBV-CTL) therapy. Researchers presented data from two clinical trials presented at the AACR Annual Meeting 2015, held April 18 to 22 in Philadelphia (Abstract CT107).

“One of the most concerning complications of blood stem cell transplantation is EBV-LPD,” said Richard J. O’Reilly, MD, Chairman of the Department of Pediatrics and Chief of the Pediatric Bone Marrow Transplantation Service at Memorial Sloan Kettering Cancer Center. “In the absence of effective therapy, these patients have an average survival time of only 16 to 56 days. The purpose of our clinical trials was to see if giving T cells from a normal-immune individual, expanded in culture and stimulated to respond to multiple proteins from the Epstein-Barr virus, could provide a safe and effective treatment.”

“The good news from our two clinical trials is that EBV-CTLs generated from either the patient’s transplant donor or from the bank of normal donor T cells put aggressive EBV-LPD that had failed to respond to rituximab into long-lasting remission in more than 60% of patients,” continued Dr. O’Reilly.

Clinical Trial Details

On March 2, 2015, the U.S. Food and Drug Administration granted breakthrough therapy designation to Memorial Sloan Kettering Cancer Center for the development of EBV-CTLs generated from the blood of third-party donors for the treatment of patients with rituximab-refractory EBV-LPD.

In the first clinical trial, 26 patients received EBV-CTLs generated from blood from their transplant donor, and 13 received human leukocyte antigen (HLA)-matched, EBV-CTLs from the Memorial Sloan Kettering Cancer Center bank of EBV-CTLs generated from third-party healthy donors.

Dr. O’Reilly explained that good treatment results were observed in this trial for patients receiving EBV-CTLs from both sources. Because EBV-CTLs from the bank are available immediately when a patient is in need, he and his team, which includes Susan E. Prockop, MD, Assistant Attending in the Pediatric Bone Marrow Transplantation Service, used only EBV-CTLs from the bank when treating the 18 patients enrolled in the second clinical trial.

High, Durable Response Rates

Among the 39 patients enrolled in the first clinical trial, 23 had a complete response, and 2 had stable disease. According to Dr. O’Reilly, 16 of those who achieved a complete response are still doing well, with 8 of these patients alive more than 5 years after their EBV-CTL treatment and 1 alive more than 10 years after treatment.

Among the 18 patients enrolled in the second clinical trial, 9 had a complete response, 3 had a partial response, and 1 had stable disease. All those who achieved a complete response continue to do well, and the researchers will be following them long term, said Dr. O’Reilly.

“The EBV-CTLs work well for the majority of recipients. However, the responses became clinically evident only after the T cells expanded in vivo, which took about 7 to 14 days. We are rigorously pursuing the development of biomarkers or other tests to predict response earlier,” concluded Dr. O’Reilly.

This study was funded by the National Cancer Institute, the Major Family Fund for Cancer Research, the Aubrey Fund for Pediatric Cancer Research, the Max Cure Fund for Pediatric Cancer Research, the Claire Tow Chair in Pediatric Oncology Research, the Julien Collot Foundation, Sportsmen for Charity, and the Stop and Shop Fund. 

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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