Gene Therapy Continues to Show Promise in Non-Hodgkin Lymphoma

The Annual Meeting of the American Society of Hematology (ASH), convened in December 2014, highlighted the expanding array of novel therapy treatments showing promise for non-Hodgkin lymphoma (NHL) patients. Covering a gamut of research from expanded analyses of recently approved therapies to promising new drugs and experimental gene therapies, the studies summarized below are just a selection of encouraging clinical results for NHL.

The experimental treatment of administering adoptive immunotherapy via the “Sleeping Beauty” gene transfer system continues to show promise in advanced hematologic malignancies. The system, originally developed at the University of Minnesota, is so named because the Sleeping Beauty gene is able to “awaken” DNA that can then replicate itself and insert the copy back into the genome. In the trial discussed at ASH, researchers used the system to create a chimeric antigen receptor (CAR) on a normal T-cell from a human immune system. The CAR was able to recognize and bind to a protein called CD19, a cell surface on B cells that is overexpressed in certain B-cell hematologic malignancies, including various subtypes of non-Hodgkin lymphoma (NHL). Forty-two patients were treated as part of the study, 22 of whom had NHL or chronic lymphocytic leukemia (CLL). The majority of the patients were treated with the CAR T-cells following a hematopoietic (stem) cell transplant, with 12 receiving the treatment for their active disease without transplant. Among the more notable outcomes, four of the five NHL patients at high risk of relapse were still in remission at 12 months, after receiving the CAR T-cells following an autologous transplant. Six of thirteen patients treated following allogeneic transplant also remained in complete remission with a median follow-up of 7.5 months.

Laurence Cooper, MD of M.D. Anderson Cancer Center and senior author on this abstract, received a Lymphoma Research Foundation (LRF) grant in 2006 to study an early version of this adoptive immunotherapy in follicular lymphoma. (LRF previously featured Dr. Cooper’s research in a 2010 Researcher Spotlight.) The researchers plan to further develop the Sleeping Beauty adoptive immunotherapy to target other common lymphoma biomarkers such as ROR1. The abstract for this study is available here.