Clinical Advances in Hematology & Oncology最新文献

Immunotherapy has transformed the treatment of acute lymphoblastic leukemia (ALL) over the past 2 decades, leading to excellent outcomes in adults and children. This is especially true in the setting of relapsed and refractory (R/R) disease, in which treatment outcomes formerly were dismal. Several immune therapies have shown efficacy and safety in the R/R setting, including monoclonal antibodies, bispecific antibodies, antibody-drug conjugates (ADCs), and chimeric antigen receptor (CAR) T-cell therapy. These new immunotherapy approaches have brought about a major paradigm shift in the treatment of R/R ALL, with very few long-term side effects in comparison with standard chemotherapy. These agents are now being used in patients with newly diagnosed ALL, with good response rates. This review discusses novel immunotherapeutic options, including bispecific antibodies, ADCs, and CAR T-cell-based therapies, in the upfront setting. It also discusses the incorporation of novel agents either as monotherapy or in combination with cytotoxic chemotherapy and describes our views on how best to use these agents in patients with newly diagnosed disease.

Antibody-drug conjugates (ADCs) have significantly advanced the treatment of breast cancer by integrating the specificity of monoclonal antibodies with the cytotoxic efficacy of chemotherapy, thereby enabling a targeted therapeutic approach that reduces off-target toxicity to normal tissues. Currently, 4 ADCs-sacituzumab govitecan, trastuzumab deruxtecan, trastuzumab emtansine, and the more-recent datopotamab deruxtecan-are approved for clinical application, with several others in advanced stages of development. Although these agents have demonstrated promising clinical efficacy, challenges such as ADC resistance and associated toxicities have emerged, underscoring the need for continued research. Multiple strategies are under investigation to enhance therapeutic benefit through combination regimens with other classes of medications, as are approaches to mitigate resistance mechanisms. Progress in next-generation ADCs, incorporating novel linkers and more potent cytotoxic payloads, holds promise for further improvement in clinical outcomes. Additionally, biomarker-driven strategies to identify those patients most likely to benefit from ADC therapy will support more personalized approaches to treatment. This review explores the structural and mechanistic features of ADCs in breast cancer, highlighting their therapeutic potential, and discusses ongoing clinical trials exploring new-generation ADCs and combination therapies.

Treatment options for hepatocellular carcinoma (HCC), the most prevalent primary liver malignancy, have historically been limited, particularly in unresectable cases with underlying cirrhosis. Initial systemic therapy with antiangiogenic agents, notably vascular endothelial growth factor (VEGF) inhibitors such as sorafenib, showed modest survival gains but lacked durable responses. Subsequent trials with more potent VEGF pathway inhibitors failed to improve overall survival significantly, raising concerns about the long-term utility and potential hepatic and renal toxicities of prolonged VEGF blockade. The advent of immune checkpoint inhibitors (ICIs) marked a paradigm shift. Trial results demonstrating that dual-ICI regimens induced more durable responses and achieved higher long-term survival rates have challenged the prior VEGF-centric therapeutic approach and suggest that early use of dual ICIs may offer a more transformative effect on disease trajectory. Although anti-VEGF therapies remain valuable for initial tumor shrinkage, prolonged use may compromise liver regeneration and worsen portal hypertension. A refined treatment strategy emphasizing VEGF inhibition for a limited duration followed by or combined with ICIs may optimize both efficacy and safety. Future research should focus on identifying predictive biomarkers for ICI response and on developing regimens that maximize long-term survival in unresectable HCC.