LAUSR

The treatment of aggressive B‐cell lymphomas is in evolution, largely based on the recognition of major genetic and biologic subtypes harboring distinct pathogenetic lesions. In this review, we will consider current treatment options with the caveat that many trials do not address some of the high‐risk subsets with enough power to conclude on definitive approaches. Since its introduction in 1976, CHOP has been the backbone of treatment in aggressive lymphomas. Efforts to improve upon CHOP have included shortening the cycle length (14 days versus 21 days), adding more cytotoxic agents, or delivering chemotherapy in an infusional regimen (ie, DA‐EPOCH‐R). However, a pivotal US intergroup study showed that “more” chemotherapy does not improve survival and only added toxicity, and serial European trials have shown that any benefit from added etoposide or shortening of the treatment cycle disappeared once rituximab was introduced. The major advance in diffuse large B‐cell lymphoma (DLBCL) came with the addition of rituximab to CHOP, which improved survival by approximately 15% to 20% across age groups, and established R‐CHOP as the standard of care. Despite the overall success of R‐CHOP, it is clear that many patient subsets are not cured (Figure 1). From a clinical perspective, elderly patients and patients with a high International Prognostic Index (IPI) have cure rates of approximately 50% (Table 1). From a biologic perspective, DLBCL has emerged as an extremely diverse disease. The 2016 WHO update highlights the heterogeneity of aggressive B‐cell lymphomas via the following changes: the requirement for cell‐of‐origin (COO) testing, the elimination of B‐cell lymphoma, unclassifiable (BCLU), and replacement by high‐grade lymphomas with shared genetic lesions (ie, dual MYC and BCL2 or BCL6 rearrangements, “double hit lymphoma [DHL]”) as a separate entity and the acknowledgement of dual expression of MYC and BCL2 (double expressor lymphomas [DEL]) as an adverse prognostic feature. With these updates in mind, should the treatment of aggressive B‐cell lymphomas be altered? Unfortunately, as the discussion below