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 combination of lenalidomide and rituximab may represent a reasonable alternative to chemotherapy for some people with previously untreated follicular lymphoma (FL), according to a study led by Dr. Peter Martin, chief of the Weill Cornell Medicine and NewYork-Presbyterian Hospital (WCM/NYP) Lymphoma Program.
Dr. Martin collaborated with the Lymphoma Program’s Drs. Jia Ruan and John Leonard, along with experts from academic medical centers across the country, to evaluate the non-chemotherapy drug combination in a phase II trial known as CALGB 50803, the results of which were recently published in the Annals of Oncology. The formalized collaboration was made possible by the Alliance for Clinical Trials in Oncology, a cooperative group sponsored by the National Cancer Institute (NCI).
Lenalidomide plus rituximab was administered over twelve 28-day cycles to 65 adults with previously untreated follicular lymphoma. Seventy-two percent of patients achieved a complete response. At five years, the overall survival rate was 100 percent, and 70 percent of patients remained free from disease progression. Rates are comparable with those typically produced by standard chemotherapy.
The study also demonstrated low rates of hematologic toxicity, such as neutropenia (low white blood cell count), lymphopenia (low lymphocyte levels) and thrombocytopenia (low platelet count), but low-grade side effects like fatigue, constipation, diarrhea and rash were commonly reported.
The results of the CALGB 50803 study do not definitively establish whether lenalidomide-rituximab is more or less toxic or more or less effective than a standard chemotherapy regimen; such insights will be clearer following completion of the randomized phase III RELEVANCE trial, which compares lenalidomide-rituximab to chemotherapy plus rituximab.
Optimal use of chemotherapy requires a careful balance of anti-tumor activity with tolerability. WCM/NYP is proud to be a leader in the discovery and development of therapies that are both active against cancer and well tolerated.
Weill Cornell’s Dr. John Leonard has been named chair of the Lymphoma Committee for the prestigious Alliance for Clinical Trials in Oncology, sponsored by the National Cancer Institute (NCI).
Dr. Leonard is the Associate Dean for Clinical Research at Weill Cornell Medical College, the director of the Joint Clinical Trials Office at NewYork-Presbyterian Hospital/Weill Cornell Medical College, and the clinical director of the Weill Cornell Lymphoma Program. An internationally-recognized hematology and oncology expert specializing in the treatment of lymphoma, Dr. Leonard has been a pioneer in the development of novel lymphoma therapeutics. .
In his role as chair of the NCI-sponsored Lymphoma Committee, Dr. Leonard will help guide the national agenda for lymphoma research by developing, supporting and shepherding Phase II and Phase III clinical trials funded by NCI at medical centers around the United States. Dr. Leonard will direct a team of lymphoma clinical and laboratory researchers from academic and community medical centers across the country to create and implement new standards of treatment as well as foster the development of novel therapeutics.
“I am honored and deeply humbled to be chosen to lead this vital national effort to improve cancer care for patients in the United States,” said Dr. Leonard. “This appointment, I believe, is a true reflection of the programs and major accomplishments we’ve made here at Weill Cornell in advancing lymphoma research and clinical care. We are recognized as a leading center internationally in contributing new approaches to lymphoma management, and I am excited to continue collaborating with colleagues both here and across the country to move the field forward and improve the effectiveness of therapies that are available for patients.”