Optimizing the monitoring of patients with DLBCL

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Principal Investigator:

Nathalie Johnson / Jewish General Hospital

Co-Investigators:

N/A

Project of $583,800 over 3 years

Supported by CQDM through:

Ministère de l’Économie, de l’Innovation et de l’Énergie du Québec (MEIE)

And by co-funding partners:

Hoffman-La Roche, JGH Foundation

The project in details:

Challenge:  Diffuse large B cells lymphoma (DLBCL) is the most common lymphoma and is curable with chemotherapy in 60% of patients. Relapsed DLBCL (rDLBCL) is frequently lethal because of resistance to chemotherapy. Chimeric antigen receptor (CAR) T cell therapy is effective in ~40% of these patients. These are “custom” immunotherapies where patients’ normal T cells are engineered to attack a protein on the surface of lymphoma cells. The reasons underlying the success or failure of this laborious and expensive process are incompletely understood, but a high tumor burden during injection is associated with poorer outcome.

Solution: Early identification of patients who are not cured with chemotherapy may improve the efficacy of immunotherapies by treating patients in a minimal residual disease (MRD) state. The research team will monitor the response to chemotherapy using tumor markers in the patients’ blood called circulating tumor DNA (ctDNA) to identify residual or emergent rDLBCL.

Expected Achievements /Impacts:  This research will result in a state-of-the-art test to detect residual rDLBCL before clinical relapse. This additional lead time will improve the success rate of this therapy by manufacturing the CAR-T before the patients become too ill, translating to improved survival of DLBCL patients. Quebec benefits by having 1) decreased use of hospital resources, 2) a better return on the investment for expensive CAR-T therapy, and 3) economic growth by stimulating research, development and production in companies involved in ctDNA testing and companies making therapies to treat de novo or relapsed DLBCL. These companies include Roche, Incyte Biosciences and Novartis. Improving the outcomes of young rDLBCL patients translates to a higher return to the work force and less disability, stimulating the economy in non-health care related areas.

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