Category: Patient Education

Mantle Cell Lymphoma: Research, Treatment, and Support at Weill Cornell Medicine

Mantle cell lymphoma (MCL) is an uncommon form of non-Hodgkin lymphoma that is tied to genetic changes in the white blood cells which makes them continually divide and accumulate within the body. MCL affects approximately 4,000 new patients each year. This form of blood cancer is unique and behaves differently in different people, meaning there is no one-size-fits-all treatment plan for all those with MCL. Each patient should undergo an evaluation for a personalized approach. Because of the diversity seen within MCL cases, this disease can be difficult to treat. However, with the help of an expert care team and research advances, new treatment milestones have been making improved outcomes possible. Listen as members of our expert team explain more about this uncommon disease here: What is Mantle Cell Lymphoma (MCL)?

The Weill Cornell Medicine (WCM) Lymphoma Program team has niche expertise in caring for patients with MCL and has been recognized as a worldwide leader in MCL research and treatment. Weill Cornell lymphoma experts utilize precision medicine and cutting-edge technologies to tailor treatments to the biological characteristics of each patient’s tumor. Hear more about the specifics of our specialized MCL program directly from some of our team members in this video about the Weill Cornell Mantle Cell Lymphoma (MCL) Program.

As part of our extensive MCL research program, MCL patients are offered access to sophisticated and precise minimal residual disease (MRD) testing that can detect lingering mantle cells in the body at a threshold of less than one in one million. MRD testing uses blood or bone marrow samples to determine if there are remaining cancer cells that may not be detected by typical scans or blood tests. This allows our physicians to assess how well the current treatment method is working, providing evidence to better tailor the approach depending on results. Some of our expert team members further break down the basics of MRD in this video. Watch to learn more: What is Minimal Residual Disease (MRD)?

Because of the disease diversity seen in many MCL cases, patients often require repeated therapies or novel approaches to treatment. Patients seen by the Weill Cornell Lymphoma Program team benefit from the expertise of physicians and researchers working together behind-the-scenes in a collaborative effort to offer the latest research and treatments to patients. Our team prides itself on our wide-range clinical trial options for patients with mantle cell lymphoma. These research studies are aimed at finding the best ways to improve the quality and length of life for all patients with MCL.

WCM is positioned as a renowned leader in mantle cell lymphoma research thanks in part to generous funding support from leading organizations including the National Cancer Institute, the Lymphoma Research Foundation, and the Leukemia & Lymphoma Society. Weill Cornell has dedicated research initiatives focused exclusively on mantle cell lymphoma and designed to develop the most effective MCL treatments by understanding the genetic underpinnings driving the disease. Learn more about Weill Cornell’s globally recognized MCL research program here: Weill Cornell Mantle Cell Lymphoma (MCL) Research.

A diagnosis with MCL can be shocking, scary, and may feel isolating at times, but the Weill Cornell Lymphoma Program is available to help patients and caregivers navigate this diagnosis and course of care by offering new patient appointments, second opinions and ongoing care for people with mantle cell lymphoma. To learn more or to make an appointment with one of our physicians, visit WeillCornell.org/Lymphoma or call (646) 962-2064.

New Research Points to HDAC3 Inhibition as a Potential Game-Changing Treatment for Specific Lymphoma Subtypes

By Sucharita Mistry, PhD

B-cell lymphomas such as diffuse large B-cell lymphoma (DLBCL) and follicular lymphoma (FL) are blood cancers of the immune cells. A vast majority of B-cell lymphomas typically display a high frequency of genetic alterations. Since lymphomas show remarkable genetic diversity, a big challenge for scientists is not only to determine which genes are mutated in these diseases, but also to identify “actionable” genetic alterations that can respond to targeted therapies.

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“Discovering how different mutations are involved in causing the disease is a major key to advancing novel mechanism-based precision therapies and immunotherapies for lymphomas, with potentially less toxic side-effects,” says Dr. Ari Melnick, a world-renowned physician-scientist at Weill Cornell Medicine.

Dr. Melnick led groundbreaking research that defines the genetic underpinnings of CREBBP mutation in lymphomas, paving the way for new therapeutic avenues. The findings of this study were recently published in Cancer Discovery.

The CREBBP gene encodes a kind of histone acetyltransferase (HAT), an enzyme that introduces small chemical tags called acetyl groups on histones, which are the major structural proteins of chromosomes. The chemical modifications on histones are termed as epigenetic changes, and they determine whether genes are turned on or off. The CREBBP gene, which is an epigenetic modifier, is frequently mutated in DLBCL and FL.

The Melnick research team, in collaboration with scientists at the MD Anderson Cancer Center, characterized the functional consequences of CREBBP mutation in lymphomas. Using a powerful CRISPR gene-editing technology, the researchers engineered lymphoma cell lines that differed only in the CREBBP mutation status. The research team discovered two different types of CREBBP mutations that either truncate the protein or inactivate the HAT domain, the latter associated with poor clinical outcomes.

This study showed that CREBBP mutation disrupts key biological pathways resulting in abnormal silencing of tumor-suppressive and antigen-presenting pathway genes. This disruption allows lymphoma cells to hide from the immune system so that they cannot be recognized and attacked by the T-cells that play an essential role in the body’s immune response.

More importantly, the malfunction in immune surveillance was restored by an HDAC3 inhibitor, a drug that specifically reverses the histone acetylation defect caused by CREBBP mutation. Notably, selective inhibition of HDAC3 reversed the epigenetic abnormalities, halted lymphoma growth and induced the expression of major histocompatibility (MHC) class II protein, enabling the T cells of the immune system to recognize and kill lymphoma cells. The research team also demonstrated that combination of an HDAC3 inhibitor with an immune checkpoint inhibitor (PD-1/PD-L1 blockade) results in synergistic anti-lymphoma immunity effects.

These findings uncover a novel mechanistic link between CREBBP mutation and immune surveillance dysfunction in lymphomas that can be counteracted by an HDAC3 inhibitor, providing a potentially game-changing approach for restoring anti-tumor immunity.

“HDAC3 inhibition provides an attractive therapeutic avenue for DLBCL and FL and may have enhanced potency in CREBBP-mutant tumors,” says Dr. Melnick. “We are very excited to translate this research into clinical trials that could potentially lead to the development of novel mechanism-based immune epigenetic therapy for CREBBP-mutant lymphomas.”

 

COVID-19 and Cancer: Helpful Resources for Lymphoma Patients

The Weill Cornell Medicine Lymphoma Program team remains committed to supporting and protecting the health and safety of our patient community during this challenging time. With COVID-19 dominating the news and impacting our everyday lives, many people may be left wondering which sources to trust and which recommendations to follow when it comes to understanding the coronavirus and staying safe during this unprecedented time.

We developed this article and compiled a handful of reliable resources designed to help lymphoma patients — at our center and beyond – best navigate this rapidly changing situation.

COVID-19 Basics and General Guidelines

Physicians and staff within the division of Hematology and Oncology at Weill Cornell Medicine and NewYork-Presbyterian Hospital are here to provide guidance and support to our cancer patients and their loved ones. We encourage you to review the information outlined in our COVID-19 and Cancer Guide, where we provide answers to our patient community’s most frequently asked questions. You are also welcome to call our COVID-19 hotline at (646) 697-4000 with questions at any time.

If you have COVID-19 symptoms or suspect that you have been in contact with someone with COVID-19, contact your oncologist for further instruction. If you need in-person medical attention, your doctor will advise you regarding the necessary steps and preparations to protect you and others at the facility before you arrive. Please do not visit your doctor’s office or the emergency department without first being in touch with your healthcare team.

COVID-19 and Lymphoma

In the Lymphoma Research Foundation (LRF) webinar entitled “Coronavirus and What the Lymphoma Community Needs to Know,” our own Dr. John Leonard reviews the current medical understanding and response to COVID-19 (per March 19, 2020). Dr. Leonard explains why we all must work together to “flatten the curve,” and addresses frequently asked questions surrounding immune system suppression and the coronavirus, lymphoma treatment during the pandemic, the use of masks and transmission of the disease between different groups such as children, the elderly and pets.

The LRF also created a COVID-19 fact sheet complete with prevention tips and questions to ask your oncologist. Weill Cornell Lymphoma Program Chief Dr. Peter Martin and an infectious disease specialist contributed to and medically reviewed this information.

Appointments and Video Visits

Please know that we remain dedicated to the health and wellbeing of our lymphoma community and that continuing to provide world-class cancer care for our oncology patients is important to us. As part of our mission to provide care during this unprecedented time, the Hematology & Oncology division has been implementing extensive patient-centered precautions. These include efforts to prevent the spread of COVID-19 within our facilities and the expansion of virtual video-based appointments.

The Weill Cornell Lymphoma Program continues to be able to offer new and current patients the cancer care they need. We also provide expert, multidisciplinary care for patients with lymphoma who need medical attention for COVID-19.

Video visits allow patients to receive high-quality lymphoma care from the comfort and convenience of their own homes, while adhering to safe social distancing parameters recommended to minimize exposure to other individuals. Our video visit capabilities also extend to patients who wish to schedule a virtual second opinion.

To schedule a video visit, please follow the instructions below. Our team will work with you to obtain any necessary medical records prior to your visit. We will inform you if we believe that you are better suited for an in-person visit.

New Patients
Please call (646) 962-2800.

Existing Patients
Please call (646) 962-2064.

Learn more about video visits. Once your video visit is scheduled, use this guide to connect with your doctor.

Video visits use the same insurance coverage as in-person appointments, and your copayment and deductible still apply.

Visitor Policy

While we recognize the value of family and friends’ support throughout lymphoma diagnosis and treatment, keeping patients and their loved ones safe requires temporary limits on the number of people allowed to accompany each patient to an appointment. Please note that our policies continue to evolve during these unprecedented times. Click here for our latest COVID-19 visitation guidelines.

Additional Resources

Patients are welcome to call the WCM/NYP COVID-19 hotline – (646) 697-4000 – with any questions. Please note that this hotline is available as a public service to provide information only, and not to diagnose, treat or render a medical opinion.

Patients may also consult the following resources.

Ways to Help

It can be easy to feel powerless in the midst of a global pandemic, but there are ways that you can help. In fact, the biggest impact that people – sick or healthy – can make in the fight against COVID-19 is simply to stay at home to curb the spread of disease and its potential to overwhelm the healthcare system.

Those willing and able to contribute to Weill Cornell Medicine and NewYork-Presbyterian’s response to COVID-19 can make a donation to support the purchasing of ventilators and personal protective equipment (PPE), and the physical and emotional wellbeing of healthcare workers on the frontlines of the outbreak.

A fundraiser was also created to provide nutritious, high-quality meals to the New York City doctors, nurses and ancillary staff leading the fight against COVID-19 as part of medical intensive care units.

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