Megan Brooks

April 19, 2015

PHILADELPHIA — One of the most serious complications that can occur in patients who receive a bone marrow transplant is Epstein-Barr virus-associated lymphoproliferative disorder (EBV-LPD), which can kill the patient within 2 months. A new study suggests that T cells obtained from the same individual who donated the bone marrow can be turned into an "off-the-shelf" treatment for this devastating complication.

EBV-specific cytotoxic T lymphocytes (CTLs) generated from a bank of normal donor T cells put aggressive EBV-LPD refractory to rituximab into long-lasting remission in more than 60% of patients in two clinical trials conducted at Memorial Sloan Kettering (MSK) Cancer Center in New York City.

The results are "striking," senior study author Richard J. O'Reilly, MD, chief of the Pediatric Bone Marrow Transplantation Service at MSK said here today at the American Association for Cancer Research (AACR) 2015 Annual Meeting.

EBV-LPD is one of the "most concerning" complications of allogeneic hematopoietic cell transplant, Dr O'Reilly added in a conference statement. "In the absence of effective therapy, these patients have an average survival time of only 16 to 56 days."

Results of these two ongoing studies suggest that T cells from a healthy donor expanded in culture and stimulated to respond to multiple EBV proteins represent a safe and effective "off-the-shelf" treatment for EBV-LPD.

In the first study, 26 patients received EBV-CTLs generated from blood from their transplant donor, and 16 (62%) had a complete response. In addition, 13 patients received human leukocyte antigen–matched EBV-CTLs from the MSK bank of EBV-CTLs generated from third-party healthy donors, and seven (54%) had a complete response.

In the second study, of 18 patients, nine (50%) had a complete response, three (17%) had a partial response, and one (6%) had stable disease. The combined complete and partial response rate was 67%.

Among all patients treated on the first protocol, "40% are alive up to 18 years posttreatment, and in the second trial, disease-free survival is almost 72%," Dr O'Reilly noted.

The overall survival in both studies "far exceeded the survival reported for this patient population," the investigators note in a meeting abstract.

Treatment with third-party EBV-CTLs has "minimal toxicities," with no grade 2 or higher acute or chronic graft vs host disease, Dr O'Reilly noted.

He said patients may need more than one cycle to achieve maximal response, "but the cycles are well tolerated, and with the achievement of complete response, the critical variable is that these are durable remissions for multiple years, and similarly, intriguingly enough, different from the chemotherapy paradigm, the partial responses are also durable in these patients for periods of years."

This study shows that T cells can be turned into an "off-the-shelf" treatment for EBV-LPD, a "devastating" and "often lethal complication" of bone marrow transplantation, commented briefing moderator Suzanne L. Topalian, MD, from the Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins in Baltimore, Maryland.

Last month, the US Food and Drug Administration granted breakthrough therapy designation to MSK for the development of EBV-CTLs generated from the blood of third-party donors for the treatment of patients with rituximab-refractory EBV-LPD.

"We are looking forward to working with our collaborators at Atara Biotherapeutics and regulators to plan the next steps," Dr O'Reilly said in a conference statement. "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."

The authors have disclosed no relevant conflicts of interest.

American Association for Cancer Research (AACR) 2015 Annual Meeting: Abstract 8841. Presented April 19, 2015.

Comments

3090D553-9492-4563-8681-AD288FA52ACE
Comments on Medscape are moderated and should be professional in tone and on topic. You must declare any conflicts of interest related to your comments and responses. Please see our Commenting Guide for further information. We reserve the right to remove posts at our sole discretion.
Post as:

processing....