CAR-T CELL THERAPY CAN INDUCE REMISSION IN REOCCURRING BLOOD CANCERS AFTER STEM CELL TRANSPLANTATION WITHOUT CAUSING GRAFT-VS.-HOST DISEASE
January 28, 2016 09:34 AM
A study co-authored by researchers from the John Theurer Cancer Center (JTCC) at Hackensack University Medical Center and the National Institutes of Health (NIH) demonstrates that chimeric antigen receptor T-cell (CAR-T) therapy can induce remission of certain blood cancers that may progress after a patient receives stem cell transplantation, while reducing the risk of a potentially fatal post-transplant complication known as graft-versus-host disease (GVHD).
The study, published this week in the Journal of Clinical Oncology, demonstrates that infusing a transplant donor’s T-cells, genetically modified to express a chimeric antigen receptor (CAR) targeting an antigen known as CD19, can induce complete or partial remission of certain blood cancers in patients who have previously received an allogeneic hematopoietic stem cell transplantation (alloHSCT). These cancers comprise most non-Hodgkin's lymphomas, some leukemias, and myelomas, and are known collectively as B-cell malignancies.
“Progressive cancers are the leading cause of death after alloHSCT, and current standard practice, which involves the use of lymphocyte infusions from the transplant donor, are often ineffective at stopping the cancer and will result in graft-versus-host disease,” said Andre Goy, M.D., M.S., Chairman, JTCC and Chief, Division of Lymphoma, HackensackUMC. “Results of the study demonstrate that infusion of anti-CD19 CAR-T cells holds great promise in treating B-cell cancers with a greatly reduced risk of GVHD, and we look to a future where this approach will play a key role in allogeneic stem cell transplantation.”
In the study, patients with B-cell malignancies after alloHSCT received a single infusion of donor CAR-T cells, with no chemotherapy or other therapies administered. Eight of 20 patients evaluated achieved remission, including six complete and two partial remissions. The response was highest for patients with acute lymphoblastic leukemia (ALL), but responses also occurred in patients with chronic lymphocytic leukemia (CLL) and lymphoma. The longest complete remission occurred in a patient with CLL, and exceeded 30 months. No patients in the study developed GVHD after infusion of CAR-T cells. The most commonly reported adverse events were fever, tachycardia and hypotension.
”It is clear that this study should be viewed as an important clinical advance,” said Andrew L. Pecora, M.D., F.A.C.P, C.P.E., Vice President of Cancer Services and Chief Innovation Officer, JTCC. “Our collaboration with NIH on this initiative is a testament to our commitment to advance research, seek better therapeutic solutions and improve clinical practice for patients with hematologic cancers.”
About the Study
The study, titled “Allogeneic T Cells that Express an Anti-CD19 Chimeric Antigen Receptor Induce Remissions of B-Cell Malignancies that Progress After Allogeneic Hematopoietic Stem-Cell Transplantation Without Causing Graft-Versus Host Disease,” was a phase 1 dose escalation trial carried out by the Experimental Transplantation and Immunology Branch of the National Cancer Institute (NCI) in partnership with JTCC. Twenty patients were enrolled in the study, with a protocol consisting of a single infusion of CAR19 T-cells from an allogeneic donor. Differentiating this study from other CAR-T cell studies was the fact that chemotherapy was not administered prior to infusion. As a result, most patients’ T-cells were not depleted at the time of infusion.
About CAR-T Cell Therapy
CAR-T cell therapy is a form of immunotherapy, widely recognized as a new and highly promising frontier in cancer therapy. CAR-T cell therapy involves engineering immune cells (from a patient or a donor) to recognize and prompt the body’s immune system to fight cancerous tumors. T cells are harvested and modified to produce CARs that improve the ability of the immune system to attack a cancer by binding to specific targets on the cancer cell.
About John Theurer Cancer Center at HackensackUMC
John Theurer Cancer Center is New Jersey’s largest and most comprehensive cancer center dedicated to the diagnosis, treatment, management, research, screenings, preventive care, as well as survivorship of patients with all types of cancer.
Each year, more people in the New Jersey/New York metropolitan area turn to John Theurer Cancer Center for cancer care than to any other facility in New Jersey. The 14 specialized divisions feature a team of medical, research, nursing and support staff with specialized expertise that translates into more advanced, focused care for all patients. John Theurer Cancer Center provides comprehensive multidisciplinary care, state of the art technology, and access to clinical trials, compassionate care and medical expertise— all under one roof. Physicians at John Theurer Cancer Center are members of Regional Cancer Care Associates, one of the nation’s largest professional hematology/oncology groups. For more information please visit www.jtcancercenter.org.