ASH Presentations on NHL Novel Therapies Highlight Expanding Options for Patients
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.
Gene Therapy Continues to Show Promise in 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 Featured Researcher profile.) 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: https://ash.confex.com/ash/2014/webprogram/Paper70178.html
Study Demonstrates Path to Chemo-Free Initial Therapy in MCL
A study combining lenalidomide (Revlimid) and rituximab (Rituxan) for mantle cell lymphoma (MCL) patients is the first to demonstrate that a chemotherapy-free treatment strategy may be effective as a first line therapy in the subtype. Currently, there is not a standardized initial treatment for MCL patients; many patients receive standard chemotherapies and combinations of chemo and immunotherapies, but those generally do not result in complete remission. Researchers presented results of a multi-center study of 38 patients treated with a combination of lenalidomide and rituximab for their initial treatment. The overall response rate was 84.2 percent, with 52.6 percent achieving a complete remission. At the time of presentation, 30 patients remained in the study without evidence of disease progression. The study is currently ongoing, but the two-year progression free survival rate is estimated at 83.9 percent.
Researchers on this study included LRF Scientific Advisory Board members Morton Coleman, MD and John Leonard, MD, both of Weill Cornell Medical College, and Sonali Smith, MD of the University of Chicago. The abstract of the presentation is available here: https://ash.confex.com/ash/2014/webprogram/Paper73280.html
New Novel Therapy Shows Promise for High-Risk CLL and SLL
A new therapy in the class of novel agents known as cyclin-dependent kinase (CDK) inhibitors, dinaciclib, has shown promise in early clinical results when used with ofatumumab (Arzerra) in relapsed and refractory CLL and small lymphocytic lymphoma (SLL). Dinaciclib, which works by targeting a group of proteins that contribute to cancer cell growth, had previously shown activity in high-risk relapsed and refractory CLL and SLL. Researchers hoped combining dinaciclib with ofatumumab, which has already been approved for use in CLL, would simultaneously target two groups of proteins and reduce the risk of hyper acute tumor lysis syndrome (TLS), a severe side effect that can develop during cancer treatment as the dying cancer cells break down. Researchers reported results through July 2014, with 36 patients treated in the study. Though the study is still ongoing, a partial response was recorded for 12 patients (33 percent), with an additional 20 (56 percent) achieving stable disease; only one patient developed TLS. Additionally, the researchers noted that the response rates improved with continued therapy -- only 13 patients completed the full therapy with the other patients discontinuing early for a variety of reasons. Further studies are needed to gain a full understanding of the effectiveness of this therapy.
Researchers on this study included two current LRF Clinical Investigator Career Development Award grantees, Farrukh Awan, MD, MS (a 2013 grantee), and Kami Maddocks, MD (a 2015 grantee), both at The Ohio State University. The abstract of the presentation is available here: https://ash.confex.com/ash/2014/webprogram/Paper75626.html
For more highlights from the 2014 ASH Annual Meeting, visit LRF's Research News and Featured Researcher sections. For more information on non-Hodgkin lymphoma, visit LRF's non-Hodgkin lymphoma factsheet.