Blastic plasmacytoid dendritic cell neoplasm: emerging developments and special considerations for 2023

The field of blastic plasmacytoid dendritic cell neoplasm (BPDCN) is rapidly evolving. Recent clinical developments in this ultra-rare hematologic malignancy have included the emergence of CD123-targeted therapies as the first generation of specific drugs approved for BPDCN. Despite the clinical improvements observed thus far in the CD123-targeted era, many patients still experience relapse and central nervous system (CNS) involvement. In addition, targeted agents for BPDCN are still not widely available around the world, resulting in major unmet medical needs in the BPDCN field. The aim of this review is to describe several emerging clinical concepts and examine special considerations in the field of BPDCN, including: (1) identification of novel markers that aid in clinically distinguishing BPDCN from other related entities; (2) the role of TET2 mutations in BPDCN; (3) the common occurrence of prior or concomitant hematologic malignancies; (4) the growing recognition of the frequency of CNS involvement in BPDCN and therapeutic strategies for prevention and treatment; (5) the ongoing clinical trials designed to build on the CD123-directed monotherapy backbone by moving the field toward combination therapy with the addition of cytotoxic chemotherapy, hypomethylating agents, BCL2-directed therapies, and central nervous system-directed therapies; and (6) the investigation of newer, second-generation CD123-targeted agents.