Global Collaboration: Lymphoma Researchers Attend Workshop at Shanghai Institute of Hematology

In early July, several researchers from the Weill Cornell Medicine/NewYork-Presbyterian (WCM/NYP) Lymphoma Program traveled to Shanghai, China to participate in the first Lymphoma Research Workshop, jointly sponsored by WCM/NYP and Shanghai Institute of Hematology (SIH). The workshop aimed to foster clinical and translational research exchange and collaboration, with the goal of further global alliance with leading Chinese institutions.

Our own Drs. Leandro Cerchietti, Peter Martin, Ari Melnick, Kristy Richards, and Jia Ruan were in attendance. Drs. Melnick and Ruan co-organized the workshop with Drs. Saijuan Chen and Weili Zhao from SIH. SIH and its affiliated Ruijin Hospital (RJH) is a leader in human genomics and lymphoma research in China.

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Dr. Ari Melnick (Left) and Dr. Jia Ruan

Dr. Melnick began by introducing the lymphoma research missions at WCM/NYP and provided an overview of our translational program, which integrates state-of-the-art genetic, epigenetic, and proteomic approaches to study lymphoma pathogenesis and inform development of mechanism-based therapeutics.

Dr. Zhao followed with a review of the recent lymphoma program developments at Ruijin Hospital, which focuses on building a multi-disciplinary diagnosis and treatment team. RJH’s translational development has been aimed at building a lymphoma biobank, next-generation sequencing, system biology, and biomarker investigations to support clinical research.

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Dr. Peter Martin (Left) and Dr. Leandro Cerchietti

On the project level, Dr. Cerchietti discussed bench-to-bedside translation of epigenetic modifying agents, such as novel treatments that sensitize chemotherapy responses in patients with diffuse large B-cell lymphoma (DLBCL). Dr. Martin then provided a comprehensive overview of the management approach for DLBCL in the U.S., reviewing important study design and findings of DLBCL clinical trials that incorporated novel agents, including epigenetic modifiers. Dr. Richards spoke about promises and challenges in canine lymphoma research in both the disease and drug development models.

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Dr. Kristy Richards

Additionally, Dr. Pengpeng Xu from RJH presented preliminary data of a phase 1 study using an epigenetic hypomethylating agent in combination with chemotherapy for DLBCL patients. This joint clinical project developed from the two institutions’ shared translational interest and expertise in exploring therapeutic potential of epigenetic agents in lymphoma.

Drs. Ruan and Melnick concluded the workshop by thanking the hosts at the Shanghai Institute of Hematology and Ruijin Hospital for their gracious hospitality. Faculty from both institutions are impressed by the progress of the ongoing collaboration and support further development of translational and clinical projects in the future, including academic exchange and joint translational and clinical trials.

 

FDA Approves Subcutaneous Administration of Rituximab for Three Lymphoma Types

On June 22, 2017, the United States Food and Drug Administration (FDA) approved subcutaneous injection of rituximab plus hyaluronidase human for people with follicular lymphoma (FL), diffuse large B-cell lymphoma (DLBCL), and chronic lymphocytic leukemia (CLL). Subcutaneous administration refers to the method of delivering a drug under the skin rather than directly into a vein as performed during intravenous (IV) administration.

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Administration of rituximab under the skin tends to take less than 10 minutes, whereas the traditional IV method can last several hours. The technique also allows for fixed dosing, which can reduce preparation time and excess drug waste, and may be more cost effective than IV infusion.

The approved treatment is to be employed only after patients have received at least one cycle of intravenous rituximab.

Approval comes based on the results of a series of clinical trials demonstrating comparable safety and efficacy outcomes across subcutaneous and intravenous administration.

FDA-Approved Drug to Treat Viral Infections Shows Promise Against Lymphomas

Ribavirin, a drug that has been approved by the Food and Drug Administration (FDA) to treat hepatitis C, as well as some viral respiratory infections and viral hemorrhagic fevers, has shown promising activity against some types of lymphoma. There is a growing movement to repurpose older drugs that might have mechanisms of action that could benefit cancer patients.

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Dr. Leandro Cerchietti

Based on preclinical work performed in the laboratory of Dr. Leandro Cerchietti, the Weill Cornell Medicine and NewYork-Presbyterian Lymphoma Program is planning a clinical trial examining the oral antiviral drug ribavirin in patients with two non-Hodgkin lymphoma subtypes, slow growing follicular lymphoma and mantle cell lymphoma. This clinical trial will be led by principal investigator Dr. Sarah Rutherford.

Previously, physicians and scientists in the Weill Cornell Medicine Lymphoma Program have demonstrated that ribavirin may be able to inhibit lymphoma cell growth. Dr. Cerchietti’s laboratory research has shown that the eukaryotic translation initiation factor 4E (eiF4E) is blocked by ribavirin in B-cell lymphoma cell lines, as well as in patient-derived xenograft (PDX) models, which more closely resemble the way cancer behaves in the human body. Blocking eiF4E ultimately leads to decreases in key proteins (MYC, BCL2, and BCL6) which are crucial for lymphoma cells’ survival.

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Dr. Sarah Rutherford

Additionally, Dr. Rutherford conducted a retrospective review of patients with lymphoma who underwent stem cell transplants at NewYork-Presbyterian Hospital/Weill Cornell Medicine. Patients who were treated with ribavirin for viral infections just before or after their stem cell transplant had better lymphoma-related outcomes compared to what was expected based on their disease risk profiles.

This clinical trial, run by Dr. Rutherford and Dr. Cerchietti, will enroll patients with follicular lymphoma and mantle cell lymphoma, and they will receive 3-6 months of oral ribavirin. Using a blood test, Dr. Rutherford and Dr. Cerchietti will monitor for the presence of a marker of lymphoma in the blood to confirm that ribavirin has the intended anti-lymphoma effect.

“We are excited about opening this clinical trial and aim to conduct additional trials in the future that combine ribavirin with other drugs,” said Dr. Rutherford. “Our goal is to ultimately develop a well-tolerated, targeted oral regimen to control lymphomas.”

This preclinical research is supported by a Translational Research Program from the Leukemia and Lymphoma Society (LLS) awarded to Dr. Cerchietti.

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