Double-hit and double-expressor B-cell lymphomas: Current treatment strategies and impact of hematopoietic cell transplantation

Abstract

High-grade B-cell lymphoma with rearrangement of MYC and BCL2 and/or BCL6 (double-hit lymphoma: DHL) was newly categorized as a subtype in the 2016 revision of the WHO classification of lymphoid neoplasms. DHL is a rare entity accounting for <10% of DLBCL and clinical data of DHL cases are still limited. Standard rituximab-incorporated chemotherapy was reported to be underpowered for this intractable disease, and some promising results with intensified regimen including dose-adjusted EPOCH-R (rituximab, etoposide, vincristine, adriamycin, cyclophosphamide, and prednisone) have been emerging. The benefit of intensified regimen for DHL patients should be determined in randomized trials. The role of consolidative autologous (auto) hematopoietic cell transplantation (HCT) for newly diagnosed cases has been also undetermined. In regards to salvage chemotherapy followed by auto-HCT for chemotherapy-sensitive relapsed cases, the prognosis seems to be unsatisfactory in patients with DHL, and novel treatment strategies to incorporate effective salvage, auto-HCT and maintenance treatment after auto-HCT are warranted. Clinical application of allogeneic (allo)-HCT has not been established in newly diagnosed and refractory/relapsed (ref/rel) cases. Recently, favorable survival data of allo-HCT for ref/rel DHL was reported. To clarify the indication of various treatment strategies, larger-scaled studies or new prognostic models for DHL are required. As another topic, clinical investigation of several novel agents such as BCL2 inhibitor is conducted along with DLBCL. Here, we summarize the data relating to DHL focusing on the application of HCT, and also discuss about the combination therapy using novel agents in the setting of HCT.