Sarah Rutherford MD – New Developments in Lymphoma

2018 American Society of Hematology (ASH) Annual Meeting

The American Society of Hematology (ASH) is the world’s largest professional society serving clinicians and scientists who work to conquer blood diseases. The ASH Annual Meeting & Exposition brings together over 25,000 hematology professionals from around the world to discuss the understanding, diagnosis, treatment, and prevention of disorders affecting the blood, bone marrow, and immunologic, hemostatic and vascular systems.

This year, the ASH Meeting celebrated its 60th anniversary in San Diego, CA. As always, our team was proud to contribute new lymphoma discoveries for presentation at the meeting. Here are some research highlights from our team.

Dr. John Leonard led a global phase III clinical trial comparing the efficacy and safety of combined lenalidomide plus rituximab versus rituximab alone in people with previously treated indolent lymphoma, including follicular and marginal zone lymphoma. Results demonstrating lenalidomide-rituximab as an important new treatment option for this patient population.

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Dr. Richard Furman and colleagues found that at follow-up of up to seven years, ibrutinib demonstrated sustained activity in both first line and relapsed/refractory chronic lymphocytic leukemia (CLL) patients.

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Dr. Peter Martin led a study examining the safety and efficacy of CC-486, also known as oral azacitidine, plus R-CHOP chemotherapy in people with diffuse large B-cell lymphoma (DLBCL).

Using a combination of human, animal, and cell line data, Jude Phillip, PhD, of the Leandro Cerchietti Research Lab, and colleagues found that the internal architecture of lymphomas present important insights into disease progression.

Dr. John Allan presented a preliminary update of an ongoing first-in-human study of vecabrutinib in patients with advanced B-cell malignancies.

Dr. Sarah Rutherford reported data that may support the elimination of bone marrow biopsies in follicular lymphoma and diffuse large B-cell lymphoma clinical trials.

Dr. Richard Furman and colleagues found that venetoclax is well tolerated and produces high levels of response in previously treated Waldenstrom’s macroglobulinemia patients.

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We are proud of our team’s continued commitment to advancing the overall understanding of lymphoma and improving clinical outcomes and quality of life for all those affected by the disease.

New Clinical Trial: A Phase 1 Study to Assess Safety/Tolerability of REGN1979 & REGN2810 in Patients with B-Cell Malignancies

The Weill Cornell Medicine Lymphoma Program has recently opened a new clinical trial for men and women with B-cell non-Hodgkin lymphoma. The study sponsor is Regeneron Pharmaceuticals, Inc., and the principal investigator at Weill Cornell is Sarah Rutherford, M.D. For more information about the study, please call Rita Gazivoda, RN at 212-746-0702 or e-mail Rita at rig9021@med.cornell.edu.

Key Eligibility

Men and women age 18 and older with either B-cell non-Hodgkin lymphoma with active disease that is either refractory to or relapsed after most recent prior therapy for whom no standard of care options exist or documented Hodgkin lymphoma with active disease not responsive to prior therapy or relapsed after prior therapy for whom no standard of care options exist.
Detailed eligibility reviewed when you contact the study team.

Study Summary

This clinical trial is for men and women with lymphoma for whom no standard of care options exist. Currently available treatments for lymphoma are effective in some patients, however, other patients experience relapse or refractory disease following treatment. Therefore, there is a need to find more effective treatments when patients fail to respond to existing standard of care options. Patients will be administered REGN2810 intravenously every 2 weeks at a specified dose level. Patients will receive REGN2810 for a minimum of 12 doses (24 weeks) and up to a maximum of 24 doses (48 weeks). Upon completion of treatment, there will be a 24-week follow-up period. Patients will continue on treatment as long as they are responding to therapy and not experiencing unacceptable side effects.

New Approach to Treating Aggressive B-cell Lymphomas

In a study published in February 2016 in Blood, researchers from Leandro Cerchietti’s lab at Weill Cornell Medicine in collaboration with the University of Montreal identified a potential new strategy for the treatment of aggressive diffuse large B-cell lymphomas (DLBCL) called double and triple hit lymphomas.

What are double and triple hit lymphomas and why they are they so difficult to treat?

Double and triple hit lymphomas have chromosomal changes in two or three genes (MYC, BCL2, and/or BCL6) which encode for proteins that have a primary role in cell growth and contribute to the development of cancer. Chemotherapy does not work well to kill these types of lymphomas. Further, patients with double and triple hit lymphomas are often older and have difficulty tolerating aggressive chemotherapy. Therefore it is essential for new, targeted therapies to be developed that are less toxic for these patients.

What did researchers find?

The researchers found that the combination of an FDA-approved antiviral medication called ribavirin and a new targeted medication called an Hsp90 inhibitor work together to kill double and triple hit lymphomas in preclinical models. Ribavirin blocks the function of a protein called eIF4E. With the inhibition of Hsp90 and eIF4E, the proteins MYC, BCL2, and BCL6 are less effective in promoting growth of lymphoma cells. The addition of ribavirin also may prevent developing resistance to treatment with the Hsp90 inhibitor.

What do these findings mean for patients?

The lymphoma group at Weill Cornell Medicine is developing a phase I clinical trial to determine the optimal dose of an Hsp90 inhibitor and ribavirin for patients with aggressive DLBCLs that do not respond or return after initial therapy. We will evaluate tumor and blood samples before and after treatment with this combination to confirm that it negatively impacts MYC, BCL2, and BCL6 as expected. This is a promising treatment strategy in these patients and expected to be much better tolerated than chemotherapy.

Stay tuned for future updates regarding treatments for double and triple hit lymphomas at Weill Cornell.

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