Double hit and double expressors in lymphoma: Definition and treatment

Emerging biologic subsets and new prognostic markers are significantly and adversely affecting curability after standard chemoimmunotherapy for aggressive B‐cell lymphomas. The identification of concurrent MYC and B‐cell CLL/lymphoma 2 (BCL2) deregulation, whether at a genomic or protein level, has opened a new era of investigation within the most common subtype of aggressive B‐cell lymphomas. Double‐hit lymphoma (DHL), defined as a dual rearrangement of MYC and BCL2 and/or B‐cell CLL/lymphoma 6 (BCL6) genes, is an uncommon subset accounting for 5% to 7% of all diffuse large B‐cell lymphomas (DLBCLs), and long‐term survivors are rare. Double‐expressor lymphoma (DEL), defined as overexpression of MYC and BCL2 proteins not related to underlying chromosomal rearrangements, is not a distinct entity in the current World Health Organization classification but accounts for 20% to 30% of DLBCL cases and also has poor outcomes. There are many practical considerations related to identifying, determining the prognosis of, and managing DHL and DEL. Double‐hit lymphoma and double‐expressor lymphoma have been increasingly recognized as aggressive subsets of diffuse large B‐cell lymphoma associated with an inferior prognosis. This review provides a comprehensive overview of their disease biology, clinical features, diagnostic testing considerations, and current treatment strategies.