Clinical Advances in Hematology & Oncology最新文献

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.

The treatment landscape for multiple myeloma (MM) has evolved significantly over the last decade with the approval of novel therapies and combinations in the newly diagnosed and relapsed/refractory settings. There has also been a shift toward a risk-adapted approach to induction and maintenance regimens, with the goal of achieving better response rates for those with high-risk disease. The incorporation of anti-CD38 monoclonal antibodies into induction regimens has led to longer progression-free survival and higher rates of measurable residual disease negativity. In the relapsed setting, the emergence of B-cell maturation antigen-directed therapy, including antibody-drug conjugates, chimeric antigen receptor T-cell therapy, and more recently, bispecific antibodies, has produced deep and durable responses in heavily pretreated patients. This review article describes novel approaches to the treatment of MM in both the newly diagnosed and the relapsed/refractory setting.

The landscape for the treatment of patients with relapsed or refractory (R/R) large B-cell lymphoma (LBCL) has continued to evolve. However, challenges continue to exist, particularly in patients who do not respond to first-line anti-CD20 monoclonal antibody and anthracycline-based therapy or those who experience early relapse. In such patients, the treatment paradigm has changed little in the past 2 decades, with salvage chemotherapy followed by myeloablative chemotherapy and autologous hematopoietic stem cell transplant resulting in historical durable response rates of approximately 40%. Given the success of chimeric antigen receptor (CAR) T-cell therapy in the third- or later-line in the R/R LBCL setting, 3 recent clinical trials (ZUMA-7, BELINDA, and TRANSFORM) have sought to address the clinical need for improved therapies in the high-risk second-line setting for primary R/R disease in the first 12 months. In this review, we analyze these 3 pivotal trials with a focus on clinical trial design, CAR T-cell product attributes, efficacy data, safety data, and patient-reported outcomes when compared with standard of care.