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.

IMG_6294

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.”

OncLive State of the Science Summit

We’re proud to share that Dr. Peter Martin and Dr. John Leonard are co-hosting a State of the Science Summit on Hematologic Malignancies with OncLive in Queens on May 4, 2017.

This free event will feature educational sessions and a dinner and networking reception. All healthcare practitioners are welcome. Seats are limited, so register today: http://ow.ly/dfIx308iTis

OncLive State of the Science Agenda_Flyer

New Pre-clinical Research Shows Transcription-Targeting Drug Useful in T-cell Lymphoma

Peripheral T-cell Lymphomas (PTCL) are uncommon, but aggressive forms of non-Hodgkin lymphoma that develop from mature T cells, a type of white blood cell. The most prevalent subtypes include PTCL-NOS (not otherwise specified), AITL (angioimmunoblastic T-cell lymphoma), and ALCL (anaplastic large cell lymphoma). Patients with PTCL are usually treated with a combination of chemotherapy agents, mostly commonly CHOP (cyclophosphamide, adriamycin, vincristine and prednisone). With the exception of a rare variant called ALK-positive ALCL, only about a third of all patients could enjoy long-term disease-free survival, with most patients either having diseases resistant to treatment or recurrent after chemotherapy. As PTCL evolves, it becomes even more molecularly complex due to factors in the tumor microenvironment that make it hard to treat. Ongoing research has been performed in order to try and improve treatment options and increase overall survival for patients with this challenging disease.

To ultimately cripple tumors in patients with PTCL and eradicate the disease from the body, it’s necessary to target the molecular feature of PTCL that helps it grow. Leandro Cerchietti, M.D. Jia Ruan, M.D., Ph.D., and other collaborators from the Lymphoma Program at Weill Cornell Medicine and NewYork-Presbyterian are trying to do just that. New research conducted by the team has shown positive results for this hard-to-treat cancer.

Dr. Cerchietti and his research group have discovered that PTCL are sensitive to THZ1, a drug that targets transcription, the first step during gene expression when DNA is copied into RNA. THZ1 was developed by Dr. Nathanael S. Gray and collaborators from the Dana-Farber Cancer Institute. THZ1 works by stopping an enzyme called CDK7 (cyclin-dependent kinase 7) that controls the transcription of lymphoma genes. This interference changes the cells and primes the tumor to better respond to biologic agents, such as BCL2 inhibitors.

For this work, Dr. Cerchietti’s Lab established a collaboration with Drs. Nathanael S. Gray from Dana-Farber and Graciela Cremaschi from the Institute for Biomedical Research and the National Research Council of Argentina. After testing more than 120 FDA-approved compounds and new biologic agents from the Developmental Therapeutics Program, Division of Cancer Treatment and Diagnosis, National Cancer Institute, National Institutes of Health and the Meyer Cancer Center Pre-Clinical Oncology Pharmacy, the investigators found that PTCL are susceptible to inhibitors of the proteasome, epigenetic drugs and compounds that target transcription, like THZ1.

tcell-lymphoma-graphic_cerchietti_thz1According to Cerchietti, they decided to focus on THZ1 since it demonstrated pre-clinical activity against PTCLs harboring the hard-to-target mutation STAT3. STAT can drive T-cell lymphomas and other tumors when activated by extracellular signaling that involves the phosphorylation of intermediate proteins like JAK. Although inhibitors of JAK proteins have been developed, they are thought to be inactive in tumors harboring the STAT3 mutation that does not require the activity of JAK. STAT proteins drive tumors by inducing the transcription of oncogenes like MYC and BCL2. Since this process requires CDK7, THZ1 can decrease the activity of STAT and the production of BCL2 and other proteins.

“Growing scientific evidence supports CDK7 inhibition as a treatment approach for cancers that are dependent on a high and constant level of transcription,” said Dr. Cerchietti. “Targeting CDK7 with THZ1 offers a way to circumvent the aggressive pathway responsible for tumor growth in many cancers, but particularly T-cell lymphomas which respond more positively to BCL2 inhibitors.”

BCL2 inhibitors are a class of drugs that are being tested to treat a variety of blood cancers. Venetoclax is an FDA-approved BCL2 inhibitor that is used to treat chronic lymphocytic leukemia (CLL) with a specific mutation.

“We are excited about these research results and the potential to bring a new treatment to patients with this aggressive lymphoma who otherwise have very few options if their cancer does not respond to chemotherapy,” said Dr. Ruan who leads the T-cell lymphoma clinical program at Weill Cornell Medicine and NewYork-Presbyterian.

“We aim to create transformative medicines that control the expression of disease-driving genes and believe this treatment can provide a profound and durable benefit for patients with a range of aggressive and difficult-to-treat solid tumors and blood cancers,” said Nancy Simonian, M.D., CEO of Syros, the biopharmaceutical company that is developing a next-generation version of the THZ1 compound for clinical trials. “Building on this research, we’ve used THZ1 as the starting point to create a selective CDK7 inhibitor that has better drug-like properties for use in humans.”

According to Syros, a phase I clinical trial built on this research is slated to open later this year to test the dosing and safety in people with solid tumors. The company plans to expand into hematological malignancies once the appropriate dose has been established in the initial phase I trial.

The bulk of this work was supported by the Leukemia and Lymphoma Society through a Translational Research Program awarded to Dr. Cerchietti.

Additional Weill Cornell Medicine contributors to this research include: Florencia Cayrol, Pannee Praditsuktavorn, Tharu Fernando, Rossella Marullo, Nieves Calvo-Vidal, Jude Phillip, Benet Pera, ShaoNing Yang, Kaipol Takpradit, Lidia Roman, Marcello Gaudiano, Ramona Crescenzo and Giorgio Inghirami.