Collaboration offers new approach to tackling rare blood cancers

Personalized approaches have dramatically improved outcomes for many patients with non-Hodgkin B-cell lymphomas - blood cancers that arise in immune cells called B cells - yet the same is not true for patients with more rare lymphoma types that originate in T cells.

Peripheral T-cell lymphomas comprise diverse blood cancers that have a distinct biology, and survival rates vary widely. Lymphoma specialist Dr. Jia Ruan, Ph.D. '98, M.D. '99, a professor of clinical medicine at Weill Cornell Medicine, and her collaborators are working to change that.

"We previously thought that we could treat all non-Hodgkin lymphomas with a one-size-fits-all model," said Ruan, who is also a member of the Sandra and Edward Meyer Cancer Center at Weill Cornell Medicine and a hematologist/oncologist at NewYork-Presbyterian/Weill Cornell Medical Center. "We are learning we really have to develop personalized diagnostic, treatment and prognostic models for T-cell lymphomas."

Co-leading the T-cell lymphoma Working Group of the multicenter Lymphoma Epidemiology of Outcomes (LEO) Consortium with Dr. Andrew Feldman of Mayo Clinic, Ruan and her colleagues have helped reveal new insights on peripheral T-cell lymphoma that might lead to customized care approaches.

"The real-world perspective landmark study we recently published helped us understand what to expect with the majority of T-cell lymphoma patients who are treated with conventional chemotherapy-based treatment," Ruan said. "That provides a benchmark and allows us to identify unmet needs and determine what our clinical development strategy should be."

Ruan recently spoke with Weill Cornell Medicine about her work.

Question: How has Weill Cornell Medicine teamed up with other centers to advance lymphoma care?

Answer: Weill Cornell has been a member of the LEO consortium, which unites eight leading U.S. medical centers with expertise in lymphoma care, since it was established in 2015 with funding from the National Cancer Institute. The goal is to build and maintain a large, diverse, prospective cohort of patients with non-Hodgkin lymphoma to identify new clinical, epidemiologic, genetic, tumor and treatment factors that influence patient outcomes.

Q: How is the LEO consortium helping address the specific challenges associated with peripheral T-cell lymphomas?

A: It's the perfect resource for a rare disease such as peripheral T-cell lymphoma. It mobilizes multicenter, multidisciplinary resources to build a large-enough database that we can dive deep into the specifics of each of the more than 30 subtypes of the disease. In smaller datasets, analyzing subtypes can quickly divide and dilute the sample size, making it hard to ask questions about subtype-specific disease factors or treatment patterns. We can conduct real-world outcome analysis across various disease subtypes and identify where the needs lie, whether it is understanding the biology, developing more effective treatments or addressing the lack of access to care.

Q: What have you learned so far?

A: By focusing on over 700 patients with peripheral T-cell lymphoma within the LEO cohort, we were able to track the evolution of care with respect to initial treatment over the past 20 years. We found that, in general, the backbone of the treatment remains quite constant, which is a chemotherapy regimen developed for patients with B-cell non-Hodgkin's lymphoma called CHOP (cyclophosphamide, doxorubicin hydrochloride, vincristine sulfate and prednisone). Over time, our knowledge of the biology and classification of peripheral T-cell lymphoma has grown, and there is an expanding list of new targeted agents with clinical activity in T-cell lymphoma, setting up the stage for biology-driven therapeutic advancement.

Q: How do you think care for these patient populations can be improved?

A: We want to build beyond the backbone of CHOP and develop initial treatment tailored to specific subtypes. More importantly, we want to introduce novel agents aimed at specific biological targets. The LEO cohort data allows us to monitor the real-world impact of targeted agents such as the anti-CD30 antibody-drug conjugate brentuximab vedotin (BV) and other agents delivered in clinical trials and clinical practice settings. We are starting to see a trend of improvement with the new agent BV in the subtype of anaplastic large cell lymphoma, but the sample size of patients who received newer treatments within our current analysis remains too small. We're hoping that additional analyses as the LEO cohort grows and matures will confirm those trends. For most other subtypes, we are hoping to find therapies that can be introduced based on biological biomarkers to improve outcomes.

Q: What are the next steps for the LEO consortium's studies of peripheral T-cell lymphoma?

A: We hope to investigate whether biological differences underlie disparities in outcomes. The next phase is to develop a contemporary multi-omic characterization of the tumor biospecimens, including genomics, transcriptomics, and tumor and microenvironment interactive signals, which would give us a more in-depth understanding of potential targets for new treatments. The new data would guide how we treat our patients and the sequence in which we administer new agents based on their mutation profiles in addition to their clinical prognostic scores. It may also help us to develop precision prognostic models for patient care.

Bridget Kuehn is a freelance writer for Weill Cornell Medicine.

The full version of this interview can be found here.