A coordinated strategy for a simple, pragmatic approach to the early identification of the ultra-high-risk patient...

Diffuse large B-cell lymphoma (DLBCL) is the most frequent aggressive lymphoma seen in clinical practice. Despite huge strides in understanding its biology, front-line therapy has remained unchanged for decades. Roughly one-third of patients have primary refractory or relapse following the end of conventional first-line therapy. The outcome of patients with primary refractory disease and those with early relapse (defined as relapse less than 1 year from the end of therapy) is markedly inferior to those with later relapse and is exemplified by dismal overall survival. In this article, the authors term patients with features that identify them as being at particularly high-risk for either primary refractory disease or early relapse, as 'ultra-high-risk'. As new treatment options become established (e.g. bispecific T-cell engagers, chimeric antigen receptor 'CAR' T-cells and antibody-drug conjugates), it is likely that there will be a push to incorporate some of these agents into the first-line setting for patients identified as ultra-high-risk. In this review, the authors outline advances in positron emission tomography, widely available laboratory assays and clinical prognosticators, which can detect a high proportion of patients with ultra-high-risk disease. Since these approaches are pragmatic and able to be adopted widely, they could be incorporated into routine clinical practice.