Dr. Susan Prockop
Adoptive transfer of HLA partially-matched Epstein Barr virus (EBV)–specific cytotoxic T-lymphocytes (EBVCTLs) had limited toxicity and produced sustained responses in patients with rituximab-refractory EBV-positive B-cell lymphoma after allogeneic hematopoietic cell transplant (HCT) or solid organ transplant (SOT). Susan Prockop, MD, of Memorial Sloan Kettering Cancer Center, presented results of the phase II study (Abstract 10016) during the Pediatric Oncology II Oral Abstract Session on Monday, June 1.
The EBVCTLs used in the trial were generated from 330 normal seropositive donors, characterized with respect to EBV specificity, HLA type, and HLA restriction. The EBVCTLs were cryopreserved in a bank for use in adoptive therapy.
Thirteen SOT and 34 HCT recipients who did not respond to or relapsed after rituximab treatment received one to six courses of the T-cell infusions, with 3 weeks between each infusion to allow for observation. Eleven of the patients who underwent SOT had also not responded to one to five courses of rituximab with chemotherapy, Dr. Prockop said.
There were no reported deaths due to EBV-positive lymphoma among patients who achieved complete response (SR) or partial response (PR). The CR plus PR rate of patients who received EBVCTLs was 65% after HCT and 62% after SOT. Maximum responses were achieved after a median of two cycles of EBVCTLs, Dr. Prockop said. Two-year overall survival after SOT was 57.7% (Fig.1) and toxicity was minimal.
The bank of cryopreserved EBVCTLs yielded appropriate cell lines based on HLA partial match at two alleles and desired HLA restriction for more than 98% of patients who were referred. The bank also allowed selection of secondary EBVCTLs restricted by different shared HLA alleles for patients who did not respond to the original treatment. That approach was successfully completed seven times, Dr. Prockop said.
“The group in New York has demonstrated an incredible capacity for these T-cells to mediate antitumor responses in aggressive bulky tumors. A very high response rate has been seen by several groups since 1994…consistently against bulky disease. This is not something that antibodies alone have been able to do,” discussant Crystal Mackall, MD, of the National Cancer Institute at the National Institutes of Health, said.
In addition, Dr. Mackall said that they “put together availability of a repertoire of EBV-CTL–specific lines that can give you an incredible variety of peptides within EBV genomes and restricted to a wide array of alleles that should increase the likelihood of finding a therapeutic match,” Dr. Mackall said.
“This is really a tour de force generated over the past 20 years,” she said. There are now 330 HCT donor-derived EBV-specific T-cell lines, and the group had the foresight to realize that they should be banked in a way that enables their use for third parties. Dr. Mackall added, “None of us believed at the time that they started this that third parties would actually work, but it turns out that they do.”
The work, she said, is “proof of principle” that T cells can mediate antitumor effects against bulky, progressive tumors.
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