Back to Search
Start Over
Hitting back at lymphoma: How do modern diagnostics identify high-risk diffuse large B-cell lymphoma subsets and alter treatment?
- Source :
-
Cancer [Cancer] 2019 Sep 15; Vol. 125 (18), pp. 3111-3120. Date of Electronic Publication: 2019 Jul 09. - Publication Year :
- 2019
-
Abstract
- Diffuse large B-cell lymphoma (DLBCL) is a clinically and biologically heterogeneous disease. Diagnostic tools in the clinic can now identify distinct subsets characterized by unique molecular features, which are increasingly transforming how these patients are managed. Activated B-cell-like DLBCL is characterized by NF-κB activation and chronic B-cell receptor signaling and may be targeted with lenalidomide or ibrutinib in the relapsed setting. Germinal center-like DLBCL is enriched for activating EZH2 mutations, and encouraging activity has been observed for the EZH2 inhibitor tazemetostat, which now has a fast-track US Food and Drug Administration designation. Double-hit lymphoma is a high-grade B-cell lymphoma characterized by translocations of MYC and BCL2 and/or BCL6 and carries a poor prognosis. Intensive chemoimmunotherapy strategies appear to be superior to standard R-CHOP (rituximab combined with cyclophosphamide, doxorubicin, vincristine, and prednisone) as initial therapy, and anti-CD19 chimeric antigen receptor T cells are inducing remission in patients with relapsed/refractory disease who previously had few available options. Primary mediastinal (thymic) large B-cell lymphoma is a molecularly distinct large-cell lymphoma with clinical and molecular features that overlap with those of classical Hodgkin lymphoma. R-CHOP has been associated with an unacceptably high rate of primary treatment failure in this young population, whereas dose-adjusted EPOCH-R (etoposide, prednisone, vincristine, cyclophosphamide, and doxorubicin plus rituximab) produces durable remissions without the need for radiotherapy in most patients. For relapsed/refractory disease, immune checkpoint inhibitors targeting PD-1 have shown promising activity in chemotherapy-refractory disease, as have anti-CD19 chimeric antigen receptor T cells. Additional therapeutic targets, including JAK2, continue to be evaluated. The identification of discrete biological subsets is steadily moving us away from a "one-size-fits-all" approach in DLBCL.<br /> (© 2019 American Cancer Society.)
- Subjects :
- Antineoplastic Agents, Immunological therapeutic use
Antineoplastic Combined Chemotherapy Protocols therapeutic use
Benzamides therapeutic use
Biphenyl Compounds
Cyclophosphamide therapeutic use
Doxorubicin therapeutic use
Enhancer of Zeste Homolog 2 Protein genetics
Etoposide therapeutic use
Gene Expression Profiling
Humans
Immunotherapy, Adoptive methods
Lymphoma, Large B-Cell, Diffuse classification
Lymphoma, Large B-Cell, Diffuse diagnosis
Lymphoma, Large B-Cell, Diffuse therapy
Mediastinal Neoplasms classification
Mediastinal Neoplasms diagnosis
Mediastinal Neoplasms therapy
Molecular Diagnostic Techniques
Morpholines
Mutation
Prednisone therapeutic use
Programmed Cell Death 1 Receptor antagonists & inhibitors
Proto-Oncogene Proteins c-bcl-2 genetics
Proto-Oncogene Proteins c-bcl-6 genetics
Proto-Oncogene Proteins c-myc genetics
Pyridones therapeutic use
Receptors, Chimeric Antigen
Risk
Rituximab administration & dosage
Rituximab therapeutic use
Translocation, Genetic genetics
Vincristine therapeutic use
Lymphoma, Large B-Cell, Diffuse genetics
Mediastinal Neoplasms genetics
Subjects
Details
- Language :
- English
- ISSN :
- 1097-0142
- Volume :
- 125
- Issue :
- 18
- Database :
- MEDLINE
- Journal :
- Cancer
- Publication Type :
- Academic Journal
- Accession number :
- 31287161
- Full Text :
- https://doi.org/10.1002/cncr.32145