Diffuse large B-cell lymphoma (DLBCL), the most common form of non-Hodgkin lymphoma, has been categorized based on the cancer cell of origin as either activated B-cell (ABC) DLBCL or germinal center B-cell (GCB) DLBCL. Each subtype is associated with a certain degree of tumor vulnerability and a corresponding response to therapy.
The more that clinicians know about how a patient’s disease develops, the better equipped they are to devise an informed and precise treatment plan. Yet, between 10-20 percent of DLBCL cases are unclassified, providing little guidance for strategic intervention.
To shed light on the unclassified disease subtype and further define the composition of the ABC and GCB subtypes, the Weill Cornell Medicine and NewYork-Presbyterian Hospital Lymphoma Program’s Dr. John P. Leonard took part in an international research initiative led by the National Cancer Institute at the National Institutes of Health, with findings recently published in the New England Journal of Medicine.
Whereas prior studies of genetic subtyping investigated individual mutations, this research was among the first to examine how mutations in multiple genes may relate to disease pathogenesis and therapeutic response.
Researchers used next-generation sequencing technology to analyze nearly 600 DLBCL patient biopsy samples, contributed in part through the Lymphoma Program’s efforts in collaboration with the Alliance for Clinical Trials in Oncology. Based on the co-occurrence of genetic alterations that they observed, the team discovered four new genetic subtypes of DLBCL – MCD, BN2, N1 and EZB – enhancing science’s understanding of the genetic framework of this aggressive cancer.
“These findings will take us one step closer to potentially employing targeted agents as part of treatment for specific DLBCL subtypes,” says Dr. Leonard. “If we can specifically identify these lymphoma types and incorporate new agents that target relevant pathways, we will advance rational clinical trials with the aim to improve outcomes for patients based on the biology of their disease.”
The Lymphoma Program’s Dr. John Leonard was granted the prestigious 2017 Miriam G. Wallach Award for Excellence in Humanistic Medical Care at Weill Cornell Medicine and NewYork-Presbyterian Hospital’s Physician of the Year event, as presented by the Department of Nursing. The award honors a physician who exemplifies altruistic and humanistic qualities and displays exceptional dedication to providing outstanding, compassionate patient-centered care.
Dr. Cam Patterson, Senior Vice President and Chief Operating Officer for NewYork-Presbyterian Hospital/Weill Cornell Medicine, helped to introduce Dr. Leonard and present the award. He noted that Dr. Leonard is widely acknowledged by his colleagues both locally and nationally for his stature in the field of lymphoma research and care, especially known for his astuteness in taking on challenging cases, such as treating pregnant women with lymphoma. He is also regarded as a great partner to his nursing colleagues.
“Receiving an award that is reflective of the feelings of the nursing staff is about as good as it gets,” said Dr. Leonard.
In his acceptance remarks, Dr. Leonard described interactions with his patients staying in the hospital the previous evening. Throughout the course of his visits, conversation topics spanned serious, difficult discussions, as well as some of a more lighthearted nature, including doubles tennis and the New York Yankees.
Dr. Leonard explained that making his rounds took only a few minutes, but it was the most fun part of his day, and it made a difference to his patients. He noted that small interactions, such as sitting down to talk and certain intricacies in the way that we connect with one another, have the potential to make a huge difference in our relationships.
“These things that you do on a daily basis and don’t even think of affect patients, colleagues and trainees,” said Dr. Leonard. “If we understand that and deliberately carry it through [to practice], we can make an even greater difference for our patients.”
Chimeric antigen receptor (CAR) T-cell therapy is an emerging form of immunotherapy that leverages the strength of a patient’s own immune system to fight cancer.
Immune cells called T-cells are extracted from the patient’s blood and modified in the laboratory to produce chimeric antigen receptors, surface-level proteins that enable the T-cells to recognize and fight targeted antigenic tumor cells. The newly engineered T-cells are then cultivated in a lab before infusion back into the patient’s body, where they further multiply and go to work attacking cells that possess the antigen that they were programmed to destroy.
At the OncLive State of the Science Summit on Treatment of Hematologic Malignancies, Dr. John Leonard, who served as co-chair for the May 4 event, expressed promise in the use of CAR T-cell therapy for patients with acute lymphoblastic leukemia (ALL), in particular.
Dr. Leonard said that in a small group of clinical trial recipients with ALL, the immunotherapy has produced excellent, seemingly durable responses, and more data on CAR T-cells for patients with hard-to-treat lymphomas, like resistant forms of diffuse large B-cell lymphoma (DLBCL), are forthcoming.
While patient selection is a crucial part of interpreting the data and planning for the future, Dr. Leonard believes that the main challenges in the development of CAR T-cell therapy relate to factors of patient selection such age, comorbidities, and aggressive cancers with prohibitive wait times for engineered cells, which can take as long as several weeks depending on the specific CAR product being used.
“I think there’s no doubt that some patients benefit, but at least in the near-term, it’s going to be a relatively small number of patients that will get CAR T-cells for lymphoma,” he said.
Check out what else Dr. Leonard had to say about CAR T-cells in this video from OncLive: