Matching genetic signatures and targeted combination therapy in high-risk DLBCL
Margaret Shipp
MDDana-Farber Cancer Institute
Project Term: July 1, 2019 - June 30, 2022
Current strategies for the treatment of DLBCL do not reflect the genomic complexity of the disease. We propose to change the DLBCL treatment paradigm by linking newly defined comprehensive genetic signatures of discrete DLBCL subsets with matched targeted combination therapies. The most promising combination therapies will be evaluated in patients with relapsed DLBCL and the appropriate genetic signatures.
Diffuse large B-cell lymphoma (DLBCL) is the most common lymphoid malignancy in adults. At present, only 65% of patients with DLBCL can be cured with standard therapies, highlighting the importance of new treatment approaches. Current treatment strategies for the treatment of DLBCL do not reflect the genomic complexity of the disease. We recently characterized the full genetic signature of DLBCL and defined 5 distinct DLBCL subtypes with specific combinations of potentially actionable genetic alterations. Of importance, patients with these genetically defined DLBCL signatures had different outcomes after receiving standard induction therapy. We propose to change the DLBCL treatment paradigm by linking the newly defined comprehensive genetic signatures of specific DLBCL subsets with matched targeted combination therapies. The most promising combination therapies will be evaluated in patients with relapsed DLBCL and the appropriate genetic signatures.