Study Evaluates Safety of Cytotoxic T Lymphocytes for Rituximab-Refractory Epstein-Barr Virus

For patients who have undergone stem cell or organ transplantation, the drugs administered to prevent organ rejection can weaken the immune system, which can lead to Epstein-Barr virus-associated lymphoproliferative disorder (EBV-LPD). “Historically, the life expectancy for somebody who developed an EBV lymphoma was less than 30 days,” said Susan E. Prockop, MD, a pediatric oncologist at the Memorial Sloan Kettering Cancer Center in New York at the American Association for Cancer Research meeting.

While rituximab is a standard line of treatment for these patients, the drug induces remissions in only approximately 55 percent of patients with radiographically demonstrable disease, and the median survival for rituximab-refractory patients is 16 to 56 days. New research presented by Dr. Prockop found that more than 60 percent of patients with rituximab-refractory (EBV-LPD) responded to cytotoxic T lymphocyte (CTL) therapy.

EBV-LPD most frequently presents as malignant, high-grade, diffuse large B-cell lymphomas that do not respond to the usual first approach to these disorders, of reducing or eliminating the drugs suppressing the immune system.

In the current investigation, Dr. Prockop and researchers evaluated the safety and efficacy of EBV-CTLs in two clinical trials that included 57 allogeneic hematopoietic cell transplant patients with EBV disease.

  • Patients in the first trial (n=39) had a median age of 21 years, and 28 had failed prior therapy with rituximab.
  • Patients in the second trial (n=18) had a median age of 52 years, and all had failed prior rituximab therapy.

In both studies, patients received up to five cycles of EBV-CTL infusions, with each session consisting of one or two infusions of 106 cells/kg weekly for three weeks.

Of the 39 patients in the first study, 23 had a complete response, 1 had a partial response, and 3 had stable disease, for a complete response rate of 62 percent and a rate of non-progression of 69 percent.

In the second study, of the 18 patients who received EBV-CTLs from unrelated third-party donors, 9 had a complete response, 3 had a partial response, and 1 had stable disease, yielding rates of complete response and non-progression of 67 percent and 72 percent, respectively. Notably, the median duration of complete and partial response was 318 days in this study, and overall survival was 71.8 percent at 2 years of follow-up.

Six patients in the first study and four patients in the second study died within two months of the first EBV-CTL infusion due to disease progression, though no deaths were considered related to treatment.

“EBV-CTLs produce high response rates that are durable,” the researchers concluded. “Patients who achieved complete response had no relapses of EBV-LPD.”

“One of the most concerning complications of blood stem cell transplantation, which has transformed the lives of many patients, including those with leukemia and lymphoma, 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, and co-investigator on the trials. “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 developed at Memorial Sloan Kettering put aggressive EBV-LPD that had failed to respond to rituximab into long-lasting remission in more than 60 percent of patients.”


Reference

Prockop SE, Doubrovina E, Baroudy K, et al. Epstein-Barr virus-specific cytotoxic T lymphocytes for treatment of rituximab-refractory Epstein-Barr virus-associated lymphoproliferative disorder. Abstract #CT107. Presented at the American Association for Cancer Research Annual Meeting, April 19, 2015.

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