Abstract
Simple SummaryImmunotherapy has played a pivotal role in the management of relapsed DLBCL. Stem cell transplant and CAR T-cell therapy are curative treatment modalities for relapsed disease. Despite this, a subset of patients continues to progress, and their outcomes remain dismal. Newer therapeutic options to optimize outcomes as well as minimize toxicity are warranted.Diffuse large B-cell lymphoma (DLBCL) is a heterogeneous disease. B-cell receptor (BCR) pathway is essential for malignant B-cell growth, survival, and proliferation. Various immune cells, including T-cells and macrophages in the tumor microenvironment (TME) contribute to tumor cell survival and pathogenesis of chemo-resistance. The presence of many targets on the malignant B-cells and in the TME has led to emergence of novel therapeutic agents. Stem cell transplant is the oldest treatment modality leveraging immune system in DLBCL. Subsequently, CD20 targeting monoclonal antibody and chimeric antigen receptor (CAR) T-cell therapy changed the treatment landscape of DLBCL. Recently, multiple novel immunotherapeutic agents have been added in the armamentarium for the management of DLBCL, and many are under development. In this review article, we will review latest updates of immunotherapeutic agents in the management of DLBCL.
Highlights
Diffuse large B-cell lymphoma (DLBCL) is the most common type of non-Hodgkin’s lymphoma (NHL), representing approximately 30–40% of new cases each year
In the CORAL (Collaborative Trial in Relapsed Aggressive Lymphoma) study, relapsed 8q24/MYC positive DLBCL had an inferior 4-year progression-free survival (PFS) (18% vs. 42%) and overall survival (OS) (29% vs. 62%), with salvage chemotherapy followed by autologous stem cell transplant, when compared to MYC negative
Tremendous progress has been made in understanding the molecular pathways that are involved in the pathogenesis of DLBCL
Summary
Diffuse large B-cell lymphoma (DLBCL) is the most common type of non-Hodgkin’s lymphoma (NHL), representing approximately 30–40% of new cases each year. Double or triple hit lymphoma (DHL/THL) is a subtype of DLBCL which is characterized by MYC and BCL2 and/or BCL6 gene rearrangements by FISH, and represents 6–14% of DLBCL cases [5]. It carries the worst prognosis among all DLBCL cases [6,7,8,9]. Patients with DHITsig experience inferior outcomes after R-CHOP than those without DHITsig (5 year time to progression, 57% and 81%, respectively) These patients carry poor outcomes regardless of their MYC/BCL2 rearrangement status [13]. We routinely use rituximab in newly diagnosed and relapsed refractory settings
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