Abstract
The most common type of non-Hodgkin lymphoma in adults is diffuse large B-cell (DLBCL). There is a historical unmet need for more effective therapies in the 2nd and 3rd line setting. Emerging immunochemotherapies have shown activity in small studies of heavily pre-treated patients with prolonged remissions achieved in some patients. Anti-CD19 CAR (chimeric antigen receptor) T cells are potentially curative in the 3rd line and beyond setting and are under investigation in earlier lines of therapy. Antibody-drug conjugates (ADC’s) such as polatuzumab vedotin targeting the pan-B-cell marker CD79b has proven effectiveness in multiply-relapsed DLBCL patients. Tafasitamab (MOR208) is an anti-CD19 monoclonal antibody producing prolonged remissions when combined with Lenalidomide (LEN) in patients who were not candidates for salvage chemotherapy or autologous stem cell transplant. Selinexor, an oral, small-molecule selective inhibitor of XPO1-mediated nuclear export (SINE), demonstrated prolonged activity against heavily-pretreated DLBCL without cumulative toxicity and is being investigated as part of an oral, chemotherapy-free regimen for relapsed aggressive lymphoma. This article reviews current strategies and novel therapies for relapsed/refractory DLBCL.
Highlights
Diffuse large B-Cell Lymphoma (DLBCL) is an aggressive subtype accounting for 25–30% of Non-Hodgkin lymphoma (NHL) with an incidence of 5.6 per 100,000 persons per year [1,2]
The World Health Organization (WHO) schema classifies by cell of origin (COO) classification including germinal B-cell (GCB) subtype or activated B cell (ABC) subtype, but more recent transcriptome sequencing techniques have identified five distinct subtypes that improve the differentiation among prognostic groups in DLBCL [3,4]
In the 2017 revision of WHO classifications, DLBCL with translocations of MYC and BCL2 and/or BCL6—double-hit (DHL) or triple-hit (THL)—are reclassified as Diffuse Aggressive B-Cell Lymphomas, with more intense therapeutic regimens such as DA-EPOCH-R with CNS prophylaxis in the first line setting having a 4 year overall survival of 72.2% [5]
Summary
Diffuse large B-Cell Lymphoma (DLBCL) is an aggressive subtype accounting for 25–30% of Non-Hodgkin lymphoma (NHL) with an incidence of 5.6 per 100,000 persons per year [1,2]. SCHOLAR-1 is the most comprehensive analysis of pooled outcomes from several large studies of relapsed and refractory DLBCL (n = 636) treated with various standard of care chemotherapy regimens, and the ORR was 26%, CR rate of 7%, and median overall survival was 6.2 months [16,17]. MOS 22 mos FDA: United States Food and Drug Administration; Flu/Cy: Fludarabine/Cyclophosphamide; LD: lymphodepletion; Benda/Flu: Bendamustin/Cyclophosphamide; Pola: Polatuzumab vedotin; BR: Bendamustin and Rituximab; Ritux: Rituximab; LEN: Lenalidomide; Tafa: Tafasitamab; dx: diagnosis; DHL: Double Hit Lymphoma; THL: Triple Hit Lymphoma; R/R DLBCL: Relapsed or Refractory Diffuse Large B Cell Lymphoma; ORR: Overall Response Rate; CR: Complete Response; mOS: Median Overall Survival; mos: months; CMR: Complete Metabolic Response; po: by mouth; NR: Not Reported. §§ Excluded if not in PR or CR and received therapy within 14 weeks
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