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.

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Follicular Lymphoma

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

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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.

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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.

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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.

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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).

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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.

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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.

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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.

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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.

 

Dr. Jia Ruan and Colleagues Encouraged by Long-Term Results of Chemo-Free MCL Treatment Regimen

Mantle cell lymphoma (MCL) is a rare subtype of non-Hodgkin lymphoma that occurs primarily in older adults. The disease is typically managed in the initial treatment setting with a combination of chemotherapy and immunotherapy, which tends not to be curative and may impart toxic side effects in some patients.

In search of an effective, less toxic treatment option for those afflicted by MCL, Dr. Jia Ruan and colleagues explored an alternative regimen free of conventional chemotherapy – lenalidomide plus rituximab – to be used in the initial treatment setting. Their multi-center phase II clinical trial of the novel biological pairing was the first-ever study of a non-chemotherapy first-line MCL treatment approach.

Thirty-eight MCL patients enrolled in the trial from July 2011 to April 2014. They received lenalidomide on days 1-21 of a 28-day cycle, and rituximab was administered four times per week during the first cycle, then once every other cycle. The first 12-cycle treatment was considered induction, or initial therapy, and was followed by a maintenance phase, in which therapy is provided to prevent relapse. Treatment was continuous until disease progression, and patients had the option to cease therapy after three years if in remission.

At the 2017 American Society of Hematology Annual Meeting, the researchers examined the long-term outcomes of the trial in a 5-year follow-up analysis to reveal that the drug combination shows promise for effective management of MCL, with the majority of trial participants doing well and maintaining good quality of life. About 90 percent of patients responded to the therapy, and over 60 percent remain in remission.

The research team also measured minimal residual disease (MRD) in patients’ blood, the small number of cancer cells that may be left after treatment that have the potential to grow and cause the patient to relapse. In the small subset of patients with available tumor tissues for MRD analysis, about 80 percent of patients were found to be MRD negative, further demonstrating the novel treatment regimen’s activity and feasibility as an additional therapeutic option for people with MCL.

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Dr. Jia Ruan

“We are encouraged by the quality and durability of the responses with the biologic doublet of lenalidomide plus rituximab as initial therapy for mantle cell lymphoma,” said Dr. Ruan. “We hope to bring this active combination to larger studies where it can be combined with other agents and compared to conventional chemotherapy.”

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

SOSS_Jia_RuanT-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: