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.