Toward An Understanding of Molecular DLBCL Subtypes

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Continued, deliberate exploration of the molecular pathways involved in different subsets of the disease is crucial to achieve clinical advances in the future.
Continued, deliberate exploration of the molecular pathways involved in different subsets of the disease is crucial to achieve clinical advances in the future.

Diffuse large B cell lymphoma (DLBCL) is the most frequently diagnosed non-Hodgkin lymphoma in adults. Clinical signs include the triad of “B symptoms:” weight loss, fever, and night sweats.

DLBCL is, however, really an “umbrella” diagnosis — a collection of biologically heterogeneous malignancies, noted Ricardo C.T. Aguiar, MD, PhD, professor of medicine in the Division of Hematology and Medical Oncology at the University of Texas Health Science Center at San Antonio. The fundamental molecular distinction is the differentiation of germinal center B cell–like (GCB) from activated B cell–like (ABC) subtypes, but more detailed genomic study is yielding other clinically relevant insights.1,2

“Great strides have been made in characterizing the molecular and cellular intricacies that drive DLBCL development and progression,” Dr Aguiar and a co-author reported in a review of how DLBCL biology is informing treatment decisions and the development of therapeutic agents.1 “The genetic landscape of DLBCL is vast and the molecular and cellular biology of the disease is complex.”

As the genomic underpinnings of DLBCL variants become better understood, molecular testing will inform treatment decision-making — and point the way toward new treatment strategies, Dr Aguiar said. Treatment options are, however, still limited, with rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) immunochemotherapy remaining, for now, the standard of care for first-line treatment.

Tumors should be tested for MYC/BCL2/BCL6 translocations, molecular subtyping for ABC, GCB or unclassifiable DLBCL (using the Lymph2Cx assay or, alternatively, immunohistochemistry [IHC]), Dr Aguiar advised. MYC/BCL expression should also be assessed using IHC.

The evidence base is, however, still young, he noted: “although some of these features certainly influence treatment response and outcome, they should not per se dictate treatment strategy.

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