Abstract Anti‐B cell maturation antigen (BCMA) therapies, including antibody‐drug conjugates, chimeric antigen receptor T cells, and bispecific antibodies (bsAbs), have recently revolutionized the treatment landscape of multiple myeloma. This review outlines the biologic rationale for targeting BCMA and sheds light on the mechanism of action of bsAbs and the main reasons behind loss of response and treatment resistance. Moreover, available safety and efficacy information on approved agents (i.e., teclistamab, elranatamab, and linvoseltamab) are described, focusing on the most relevant treatment‐related toxicities, including cytokine release syndrome, immune effector cell‐associated neurotoxicity syndrome, cytopenias, and infections, and established approaches for their monitoring and management. Furthermore, available data on active trials evaluating the use of bsAbs in combination with other agents and/or in earlier lines of therapy are discussed, as well as emerging data on novel anti‐BCMA bsAbs in clinical development, such as etentamig. Finally, the use of bsAbs beyond multiple myeloma has been explored by reviewing clinical trials and real‐world experiences in other monoclonal gammopathies (e.g., smoldering multiple myeloma and light‐chain amyloidosis) or other conditions, such as autoimmune diseases. Overall, the objective of this review was to provide a comprehensive overview on the role of BCMA‐targeting bsAbs while discussing future developments in this field, including their use across different settings and combinations strategies, as well as the ongoing efforts to improve safety and tolerability through the implementation of specific guidelines for toxicity management.
Abstract Background Obesity is a recognized risk factor for renal cell carcinoma (RCC) incidence, but higher body mass index (BMI) measured at diagnosis has been paradoxically associated with improved survival. This study investigated whether postdiagnosis changes in BMI and metabolic comorbidities combined with BMI at diagnosis are associated with survival. Methods This study examined 1289 patients with nonmetastatic RCC (stage I–III) from the Oncology Research Information Exchange Network. BMI was assessed at diagnosis and at 2 and 3 years postdiagnosis. Multivariable Cox regression and restricted cubic spline models estimated hazard ratios (HRs) for overall survival (OS) and disease‐free survival (DFS). Results Modest weight gain (<10%) and stability were most favorable trajectories. Compared with modest weight gain, postdiagnosis weight loss was associated with worse OS and DFS (>10% loss at 2 years: OS HR, 7.77; 95% CI, 3.00–20.16; DFS HR, 3.13; 95% CI, 1.68–5.82), independent of BMI at diagnosis, whereas substantial weight gain was associated with worse OS (>10% gain at 3 years: OS HR, 3.26; 95% CI, 1.14–9.32). Nonobese patients with diabetes had significantly worse DFS (HR, 1.83; 95% CI, 1.22–2.76), whereas the association between obesity and improved survival was mainly limited to patients without diabetes (HR, 0.75; 95% CI, 0.58–0.97). Conclusions Postdiagnosis weight trajectory and metabolic health are important prognostic factors for nonmetastatic RCC. Weight stability and absence of diabetes were associated with more favorable outcomes. Incorporating repeated BMI measurements and diabetes status may improve risk stratification during RCC survivorship.
