T-cell lymphoma – Page 2 – New Developments in Lymphoma

2018 American Society of Clinical Oncology (ASCO) Annual Meeting

The American Society of Clinical Oncology (ASCO) is the world’s leading organization for physicians and oncology professionals who care for people with cancer. Each year, ASCO’s Annual Meeting brings together over 30,000 oncology professionals from around the world to discuss state-of-the-art treatment modalities, new therapies and ongoing controversies in the field.

Our Lymphoma Program is proud to have been part of several research studies presented at this year’s meeting, contributing to new discoveries across a range of lymphoma subtypes. Here are the latest updates from our team:

T-Cell Lymphoma

An unmet treatment need exists for peripheral T-cell lymphoma patients, especially those with relapsed/refractory disease. Dr. Jia Ruan was part of a research team testing immunotherapy agent pembrolizumab within this patient population.

Follicular Lymphoma

Dr. Peter Martin was involved in a clinical trial investigation of acalabrutinib in treatment of follicular lymphoma, which yielded promising response rates.

Data supporting vitamin D supplementation in indolent lymphoma patients treated with rituximab were presented at this year’s meeting. Dr. John Leonard is Weill Cornell Medicine and NewYork-Presbyterian’s principal investigator evaluating the vitamin’s effects in an ongoing phase III trial. Trial information here.

ASCO18_Leonard

Diffuse Large B-Cell Lymphoma (DLBCL)

Dr. Jia Ruan was involved in the clinical trial assessment of single-agent acalabrutinib in relapsed/refractory DLBCL patients.

Waldenstrom’s Macroglobulinemia

Dr. Richard Furman was senior author on a study demonstrating acalabrutinib as an effective and well-tolerated therapy for people with Waldenstrom’s macroglobulinemia.

Chronic Lymphocytic Leukemia (CLL)

Dr. John Allan, along with Dr. Richard Furman, collaborated with research colleagues to investigate the demographic impact on incidence and treatment outcomes in people with chronic lymphocytic leukemia (CLL).

Dr. John Allan is Weill Cornell Medicine and NewYork-Presbyterian’s principal investigator for a phase II clinical trial of ibrutinib and venetoclax – two non-chemotherapeutic agents – in people with previously untreated chronic lymphocytic leukemia (CLL). Trial information here.

Non-Hodgkin Lymphoma

People with human immunodeficiency virus (HIV) are at increased risk for developing aggressive non-Hodgkin lymphomas frequently associated with two herpes viruses: Epstein-Barr virus (EBV) and Kaposi’s sarcoma-associated herpes virus (KSHV). Weill Cornell Medicine pathologist Ethel Cesarman, MD, PhD, contributed to a phase II trial conducted through the AIDS Malignancy Consortium (AMC) to test HDAC inhibitor vorinostat’s effects on HIV-related non-Hodgkin lymphoma.

Dr. Peter Martin, the Principal Investigator for the Lymphoma Epidemiology of Outcomes (LEO) consortium at Weill Cornell Medicine and NewYork-Presbyterian Hospital, aided in a study of vulnerability to undesirable outcomes in people with newly diagnosed non-Hodgkin lymphoma. Vulnerable status was measured overall, and by age, gender and clinical features.

As always, we are proud of our team’s active commitment to advancing the overall understanding of lymphoma and improving clinical outcomes and quality of life for all those affected by the disease.

Re-Thinking Epigenetic Therapies for B-Cell Lymphoma

Histone deacetylase inhibitors (HDACi) are small molecules that alter the function of histones, or proteins that bind to DNA and help to determine chromosome shape and gene activity. In cancer treatment, HDACi are traditionally considered epigenetic drugs because of their capacity to modify gene expression to halt tumor cell division, but new research from the Cerchietti Research Laboratory at Weill Cornell Medicine poses rationale for studying the inhibitors’ biological effects through a different lens – their impact on cell metabolism.

Benet Pera, Ph.D., along with Weill Cornell colleagues, as well as researchers from the Helmholtz Institute of Computational Biology in Germany and the Lady Davis Institute for Medical Research in Canada, conducted the study to improve the efficacy of HDACi in people with B-cell lymphoma, which is relatively low compared to that in T-cell lymphoma. Several HDACi, including vorinostat and romidepsin, have been approved by the United States Food and Drug Administration (FDA) for treatment of certain T-cell lymphoma subtypes.

Contrary to their namesake, histone deacetylase inhibitors are able to affect a long list of non-histone proteins, among them metabolic enzymes. These agents can be more appropriately referred to as lysine deacetylase inhibitors (KDACi). Due to the activity of KDACi in proteins involved in metabolic pathways, Pera et al. investigated the effects of the KDACi panobinostat in the cell metabolism of relapsed/refractory diffuse large B-cell lymphoma (DLBCL) patients enrolled in a phase II trial. Metabolic profiling of the patients’ plasma before and after KDACi-treatment demonstrated that panobinostat prompts DLBCL cells to rely on a certain metabolic pathway, the choline pathway, for survival. The scientists found that in the lab, treating the cancer cells with a choline pathway inhibitor in combination with panobinostat produced superior anti-lymphoma effects in vitro and in animal models.

“We are studying these so-called ‘epigenetic’ drugs from a different angle, hoping that metabolomics might hold the key to improving their clinical efficacy,” says Dr. Pera.

The research data recently published in the open-access journal EBioMedicine help to substantiate the team’s innovative re-application of epigenetic reagents, demonstrating the value and promise of the metabolic mechanisms by which KDACi/HDACi can improve current therapeutic options for people with B-cell lymphoma. The results also highlight the need to explore the unknown biological effects of this class of drugs before they can be successfully implemented in a clinical setting.

Dr. Jia Ruan Reviews Updates in T-Cell Lymphoma Research and Treatment

SOSS_Jia_Ruan T-cell lymphoma is a complex form of non-Hodgkin lymphoma caused by abnormal clonal growth of mature T-cell lymphocytes. The disease is uncommon, affecting approximately 5-10 percent of lymphoma patients in the United States.

Historically, T-cell lymphoma was classified according to histological (microscopic anatomy) features, but thanks to new technology such as next-generation DNA sequencing and gene expression profiling, we are now able to refine disease classification based on molecular features and cell of origin. Dr. Jia Ruan discussed some of these updates at the OncLive State of the Science Summit on Hematologic Malignancies.

The most common subtypes of systemic peripheral T-cell lymphoma (PTCL) are: peripheral T-cell lymphoma not otherwise specified (PTCL-NOS), anaplastic large-cell lymphoma (ALCL), and angioimmunoblastic T-cell lymphoma (AITL). Cutaneous T-cell lymphoma (CTCL) primarily affects the skin and tends to be less aggressive compared to systemic subtypes.

While outcomes vary by T-cell lymphoma subtype, the five-year overall survival rate for systemic PTCL (with the exception of ALK+ ALCL) is between 20-30 percent, which Dr. Ruan said is suboptimal and indicative of a need for progress from a clinical research and clinical management standpoint.

Physician-researchers are taking steps to improve efficacy of initial T-cell lymphoma therapy so that as many patients as possible can achieve complete remission (CR) and stay in remission for as long as possible. Strides include incorporating frontline stem cell transplant as a way to prolong progression-free survival (PFS) in a portion of patients, as well as moving novel agents into initial combination therapy.

To date, four FDA-approved novel agents, namely pralatrexate (anti-folate), romidepsin (histone deacetylase or HDAC inhibitor), brentuximab vedotin (CD30 antibody-drug conjugate), and belinostat (HDAC inhibitor), are being evaluated in clinical trials for evidence of enhanced effectiveness when combined with cyclophosphamide, doxorubicin hydrochloride, vincristine, prednisone (CHOP)-like chemotherapy. Clinicians eagerly await the results of these studies.

In CTCL, Weill Cornell Medicine (WCM) and NewYork-Presbyterian’s (NYP) multidisciplinary approach to healthcare allows medical oncologists and dermatologists to collaboratively diagnose and manage cases, as well as offer a range of treatment options. For cases with thin layers of skin involvement, skin-directed therapies include steroids, topical chemicals, light therapy, and electron beam radiation. For cases that progress from the skin to the lymphatic and blood system, treatment may include systemic agents like romidepsin, retinoid analogues like bexarotene, and vorinostat, an oral HDAC inhibitor. Combinations of topical therapy and systemic treatment, as well as novel options through clinical trials, are also considered whenever appropriate.

At the Lymphoma Program at WCM/NYP, the overarching goal in the context of T-cell lymphoma is to use cutting-edge next-generation sequencing of patient samples in order to better understand T-cell lymphoma biology, and to then apply a personalized approach to pair patients with the appropriate clinical trials and optimal conventional therapies.

Watch Dr. Ruan speak with OncLive about classification of T-cell lymphomas in this video:

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