$4M Grant Awarded to Weill Cornell Medicine Lymphoma Program for Mantle Cell Lymphoma Research

Weill Cornell Medicine (WCM) was selected by the Leukemia and Lymphoma Society (LLS) as the only medical institution in New York and one of two sites nationwide to receive a highly competitive grant to improve therapies for mantle cell lymphoma (MCL) patients.

The LLS Mantle Cell Lymphoma Research Initiative (MCL-RI) award of $2.5 million couples with significant matching from WCM to total over $4 million worth of funding provided to accelerate the movement of innovative MCL treatment approaches from the laboratory bench to the patient bedside. The LLS award was sourced in part by generous philanthropic investments supporting the future of cancer research.

The MCL-RI prompted an intra- and inter-institutional collaboration among physicians and researchers at WCM and the Ohio State University Comprehensive Cancer Center, who together leveraged a unique blend of scientific and clinical expertise, state-of-the-art technology and reagents developed in-house to combat drug resistance in mantle cell lymphoma.

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Weill Cornell Medicine From left to right (Back): Maurizio Di Liberto, PhD; Peter Martin, MD; Karla Ballman, PhD; Lorenzo Galluzzi, PhD; John Leonard, MD From left to right (Front): Olivier Elemento, PhD; Jihye Paik, PhD; Selina Chen-Kiang, PhD; Jia Ruan MD, PhD; Lewis Cantley, PhD Not pictured: Xiangao Huang, PhD; Giorgio Inghirami, MD; Christopher Mason, PhD

The team devised a set of research projects that will ultimately accomplish two major goals via two clinical trials of targeted agents. Goal number one is to define the genomic basis and molecular mechanisms for drug resistance in MCL, and two, to develop therapeutic strategies that overcome this drug resistance.

In preliminary research, the collaborative group analyzed the MCL genes and proteins of individual patients before, during and after treatment with palbociclib, a drug that targets proteins CDK4/6. In healthy cells, CDK4/6 help to dictate the cell cycle prior to division, but in MCL cells, these proteins malfunction, leading to uncontrolled proliferation – the underlying cause of drug resistance and disease progression.

Research at WCM demonstrated that prolonged inhibition of CDK4 not only prevented proliferation of MCL cells, but also made them more sensitive to killing by other drugs, such as ibrutinib, a BTK inhibitor used extensively in MCL treatment. The team found that CDK4 inhibition resulted in architectural changes in DNA and inactivation of the PI3K enzyme – and that these changes were the first steps toward reprogramming MCL cells for a deeper, more durable response to treatment. A phase I clinical trial combining palbociclib + ibrutinib (PALIBR) in recurrent MCL produced responses that were indeed much deeper and longer lasting than those from ibrutinib alone.

Ohio State University From left to right (Back): Jonathan Brammer, MD; Rosa Lapalombella, PhD; Sabarish Ayyappan, MBBS; Lapo Alinari, MD, PhD;  Farrukh Awan, MBBS; Basem William, MBBCh  From left to right (Middle): Robert Baiocchi, MD, PhD;  Geetika Bhatt, MBBS; Mollie Moran, CNP; Elizabeth Joseph; Beth Christian, MD From left to right (Front): Gretchen McNally, CNP; Corinne Hoffman, CNP; Julie Molina, CNP; Samantha Campolo, CNP; Annette Staub, CNP; Kami Maddocks, MD Not pictured: David Bond, MD; Narendranath Epperla, MBBS, MS; Deepa Sampath, PhD; Dena Uscio, CNP

A forthcoming multicenter phase II clinical trial of PALIBR in recurrent MCL will aim to define the patient subgroups most likely to benefit from this therapy. By studying the MCL genomes of individual patients in the phase II PALIBR trial over time, researchers will identify the mutations associated with drug-resistance and then target the resistance-specific mutations that they discover.

Following prior trial results showing the combination of lenalidomide with rituximab to be clinically active and well tolerated in patients with previously untreated MCL, the team will also conduct a multicenter phase II trial of a lenalidomide- plus- rituximab- based combination regimen in untreated MLC, using real-time molecular blood testing to modify therapy. Researchers will then evaluate whether these treatment modifications improve tolerability and practicality without compromising efficacy.

The team expects that the proposed projects will shed new light on the genomic basis and mechanisms for drug resistance in MCL, uncover novel resistance biomarkers and lead to the development of individualized therapies that overcome drug resistance in MCL – all of which have profound implications for the treatment of MCL and other blood cancers.

“Our mission to understand and conquer drug resistance with personalized new therapies that are long lasting and less toxic is rooted in deep science, cutting-edge technology, a commitment to advance MCL therapy and seamless clinical and translational collaboration within our team,” said Selina Chen-Kiang, Ph.D., the joint initiative’s director. “In the era of genomics and targeted drugs, we believe our unique synergy, along with the support of MCL-RI funding, will enable us to learn how MCL evolves over time and who will most likely benefit from novel therapies.”

2017 American Society of Hematology Annual Meeting and Exposition

Our Lymphoma Program researchers and physicians made a massive impact at this year’s American Society of Hematology (ASH) Annual Meeting and Exposition, an educational gathering of over 25,000 clinicians and scientists from around the world who are working to conquer blood disease.

Our team was involved in nearly 50 study abstracts presented at the meeting, helping to advance the overall understanding of lymphoma, as well as improve clinical outcomes and quality of life for those affected by the disease. Here are some highlights of our research:

Our physicians, as well as a Weill Cornell Medicine and NewYork-Presbyterian second-year resident, presented exciting data on promising new treatment strategies for patients across several disease subsets, including mantle cell lymphoma (MCL), diffuse large B-cell lymphoma (DLBCL), and follicular lymphoma (FL). Program chief Dr. Peter Martin was also invited to lead two educational programs regarding ways to optimize therapy for mantle cell lymphoma. His paper, on which the educational programs were based, was selected for inclusion in the American Society of Hematology Education Book.

Initial Treatment with Lenalidomide Plus Rituximab for Mantle Cell Lymphoma: 5-Year Follow-up and Correlative Analysis from a Multi-Center Phase II Study


A Phase I, Open-Label, Multicenter Trial of Oral Azacitidine (CC-486) Plus R-CHOP in Patients with High-Risk, Previously Untreated Diffuse Large B-Cell Lymphoma, Grade 3B Follicular Lymphoma, or Transformed Lymphoma  


Phase 1 Clinical Safety, Pharmacokinetics (PK), and Activity of Apilimod Dimesylate (LAM-002A), a First-in-Class Inhibitor of Phosphatidylinositol-3-Phosphate 5-Kinase (PIKfyve), in Patients with Relapsed or Refractory B-Cell Malignancies


Randomized Phase 2 Trial of Ofatumumab and Bendamustine Versus Ofatumumab, Bendamustine, and Bortezomib Induction and Maintenance Therapy in Patients (pts) with Previously Untreated High Risk Follicular Lymphoma (FL): Results from CALGB 50904 (Alliance)

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Venous Thromboembolism in Patients with B-Cell Non-Hodgkin Lymphoma (NHL) Treated with Lenalidomide


Acalabrutinib Monotherapy in Patients with Relapsed/Refractory Chronic Lymphocytic Leukemia: Updated Results from the Phase 1/2 ACE-CL-001 Study

Acalabrutinib is a second-generation inhibitor of Bruton’s tyrosine kinase (BTK) with apparent efficacy equivalent to that of first-generation inhibitor ibrutinib but fewer toxicities due to it being more selective for BTK. In this first study of acalabrutinib in chronic lymphocytic leukemia (CLL), acalabrutinib demonstrated excellent efficacy, durability and tolerability, with an overall response rate of 93 percent and an estimated 18-month progression-free survival rate of 88 percent.

– Richard Furman, MD

Weill Cornell Medicine pathologists, as well as researchers from the laboratories of Drs. Leandro Cerchietti, Ari Melnick and Dan Landau also made significant pre-clinical contributions that boost our knowledge of lymphoma on a molecular and genetic level.

Generation and Application of T-Cell Lymphoma Patient Derived Tumor Xenograft Models

We generated innovative models for directly transplanting human lymphomas into mice and demonstrated that these models closely resemble the way that the disease behaves in humans. We anticipate that this will represent a unique tool for the development of therapeutic options tailored to individual patients’ specific genetic profile and medical history, also known as precision medicine.

– Danilo Fiore, PhD

Integrative Analysis of 1001 Diffuse Large B Cell Lymphoma Identifies Novel Oncogenic Roles for Rhoa 


HSP90 Facilitates Oncogene-Induced Metabolic Reprogramming in B-Cell Lymphomas

We describe a novel function of HSP90, a protein considered to influence cancer cells’ ability to proliferate and survive by working as a stabilizer of a large array of proteins required for oncogenesis. Our data suggest that in lymphoma, HSP90 contributes to establishing higher efficiency metabolic networks that support the metabolic stress imposed by MYC, a key gene in lymphomagenesis with the potential to contribute to lymphoma cells’ metabolism and growth. This knowledge provides actionable targets for potential combination therapies with HSP90 inhibitors.

– Maria Nieves Calvo Vidal, PhD

Development of a Novel Class of Microtubule Destabilizing Agents with Selectivity Against Diffuse Large B-Cell Lymphoma (DLBCL) with B-Cell Receptor (BCR) Activation

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Single Cell Joint Methylomics and Transcriptomics Define the Epigenetic Evolution and Lineage Histories of Chronic Lymphocytic Leukemia

Epigenetics are mechanisms that control the on and off gene “switches” that can drive tumor cell growth. Aberrant DNA methylation, the best-studied epigenetic modification in lymphoid malignancies, dysregulates genes and pathways involved in the origin and development of chronic lymphocytic leukemia (CLL) pathogenesis. Like genetic alterations, DNA methylation modifications are heritable and therefore may be subjected to natural selection in cancer. We developed a single-cell DNA methylation methodology (MscRRBS) and applied it to hundreds of normal B cells and CLL cells. It revealed that CLL shows elevated but uniform abnormal DNA methylation changes across the tumor cell population, reflecting common origin from a single, transformed cell.

– Ronan Chalinge, PhD

SIRT3 Is a Novel Metabolic Driver of and Therapeutic Target for Chemotherapy Resistant DLBCLs


The Mutational Landscape and Immune Microenvironment of Primary Intestinal Follicular Lymphoma (PIFL)

Although follicular lymphoma is the most common indolent, or slow-growing, lymphoma worldwide, we lack a full understanding of the biology of the disease. In our work, we use a clinically distinct subtype, primary intestinal follicular lymphoma, to highlight features that are associated with an indolent clinical course and to further our understanding of the follicular lymphoma immune microenvironment.

– Johannes Hellmuth, MD

We are so proud of our Lymphoma Program’s leadership at ASH and of the team’s relentless work to make life better for lymphoma patients and their families. 

Dr. John Leonard Awarded for Outstanding Patient Care

IMG_6169The Lymphoma Program’s Dr. John Leonard was granted the prestigious 2017 Miriam G. Wallach Award for Excellence in Humanistic Medical Care at Weill Cornell Medicine and NewYork-Presbyterian Hospital’s Physician of the Year event, as presented by the Department of Nursing. The award honors a physician who exemplifies altruistic and humanistic qualities and displays exceptional dedication to providing outstanding, compassionate patient-centered care.

Dr. Cam Patterson, Senior Vice President and Chief Operating Officer for NewYork-Presbyterian Hospital/Weill Cornell Medicine, helped to introduce Dr. Leonard and present the award. He noted that Dr. Leonard is widely acknowledged by his colleagues both locally and nationally for his stature in the field of lymphoma research and care, especially known for his astuteness in taking on challenging cases, such as treating pregnant women with lymphoma. He is also regarded as a great partner to his nursing colleagues.

“Receiving an award that is reflective of the feelings of the nursing staff is about as good as it gets,” said Dr. Leonard.

In his acceptance remarks, Dr. Leonard described interactions with his patients staying in the hospital the previous evening. Throughout the course of his visits, conversation topics spanned serious, difficult discussions, as well as some of a more lighthearted nature, including doubles tennis and the New York Yankees.


Dr. Leonard explained that making his rounds took only a few minutes, but it was the most fun part of his day, and it made a difference to his patients. He noted that small interactions, such as sitting down to talk and certain intricacies in the way that we connect with one another, have the potential to make a huge difference in our relationships.

“These things that you do on a daily basis and don’t even think of affect patients, colleagues and trainees,” said Dr. Leonard. “If we understand that and deliberately carry it through [to practice], we can make an even greater difference for our patients.”