New England Journal of Medicine – New Developments in Lymphoma

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 United States Food and Drug Administration (FDA) recently approved brentuximab vedotin in combination with chemotherapy as a first-line treatment for people with advanced-stage classical Hodgkin lymphoma.

Also known as Adcetris, brentuximab vedotin is an antibody drug conjugate that targets the CD30 protein present on lymphoma cells and delivers a toxin designed to promote cancer cell death. The drug has been previously approved to treat systemic anaplastic large cell lymphoma (ALCL) and Hodgkin lymphoma that has returned after prior therapy.

The FDA’s approval follows the encouraging results of the phase III ECHELON-1 clinical trial, presented at the 2017 American Society of Hematology (ASH) Meeting and Exposition and published in the New England Journal of Medicine. The trial, which was open at Weill Cornell Medicine and NewYork-Presbyterian Hospital, compared standard therapy with adriamycin, bleomycin, vinblastine and dacarbazine (ABVD) versus adriamycin, vinblastine and dacarbazine plus brentuximab vedotin (A+AVD).

Of the 1,300+ enrolled patients, those receiving A+AVD were demonstrated to be 23 percent less likely to experience disease progression, a need for additional therapy, or death, as compared to the cohort receiving the standard of care therapy.

Dr. Peter Martin

“ABVD has been the standard therapy for a couple decades because it works really well, but it’s great to have new treatments available for people with Hodgkin lymphoma,” said Peter Martin, Chief of the Lymphoma Program. “I’m proud that we were able to offer this treatment at Weill Cornell a long time ago through the ECHELON-1 trial. Like any treatment, the A+AVD combination may not be right for everyone and requires consideration of side effects, like infection risk and neuropathy. Decisions between patients and physicians regarding the best treatment should follow an open discussion of the evidence.”

Tag: New England Journal of Medicine

Scientists Identify Four New Genetic Subtypes of Diffuse Large B-Cell Lymphoma

Novel Therapy Approved for Previously Untreated Hodgkin Lymphoma Patients

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