Presse Med
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Multiple myeloma (MM) is an incurable cancer of older adults. Given the aging population, the prevalence of older adults with MM is expected to further increase over the next decade. Challenges in treating older adults result from the heterogeneity of both aging itself and the disease. ⋯ The first part of our review will focus on pertinent investigations, considerations for treatment initiation and initial risk stratification, including frailty assessment prior to treatment initiation. In the second part, we will focus on the overall goals of treatment and therapeutic options for newly diagnosed and those with relapsed/refractory MM, including novel immunotherapy and supportive care. Lastly, we will end this review by highlighting current knowledge gaps and providing suggestions for future directions to further improve outcomes among older adults with MM.
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Primary systemic amyloidosis, or light chain (AL) amyloidosis, is a rare lymphoproliferative disorder in which aberrant light-chain immunoglobulins secreted into the bloodstream aggregate into fibrils and deposit into tissues, causing widespread organ damage and, if not treated, death. This review provides a comprehensive summary of the pathophysiology and manifestations of AL amyloidosis; standard-of-care diagnostic approach; typical treatment regimens; and areas of active investigation.
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Renal disease is a frequent complication of symptomatic multiple myeloma, that increases morbidity and reduces quality of life and overall survival. It may result from various lesions, the most frequent being light chain cast nephropathy (LCCN), related to precipitation of monoclonal free light chains (FLC) with uromodulin in distal tubules. Rapid identification of the type of kidney disease with appropriate management is key. ⋯ In patients with severe acute kidney injury, reinforcing chemotherapy with FLC removal through plasma exchange or high-cutoff hemodialysis may increase the probability of renal response, despite controversial data from randomized trials. Histological assessment of the extent of cast formation and interstitial fibrosis/tubular atrophy may help evaluating renal prognosis and refining therapy. Thanks to improved overall survival, renal transplantation may be considered in selected candidates with end-stage kidney disease.
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Although the prognosis of patients with multiple myeloma (MM) has been significantly improved by the introduction of proteasome inhibitors, immunomodulatory drugs and monoclonal antibodies, MM is still considered an incurable disease in the vast majority of the patients. In recent years, T-cell based immunotherapy represents a novel treatment strategy for relapsed/refractory (RR) MM. ⋯ To date, several CAR T-cell and bsAb products have already been approved for the treatment of RRMM, leading to a paradigm shift in the MM therapy and providing a potential curative option. In this review, we provide a summary of mechanisms of action, immune targets, selected clinical data, resistance mechanisms and therapy sequencing of CAR T-cell and bsAb in MM.
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Minimal Residual Disease (MRD) in multiple myeloma has emerged as a significant prognostic factor, guiding treatment strategies and enhancing patient outcomes. Despite advancements in therapies such as proteasome inhibitors, immunomodulatory drugs, monoclonal antibodies, CAR-T cell therapy, and bispecific antibodies, complete eradication of malignant plasma cells remains challenging. MRD refers to a small number of residual cancer cells that persist after treatment and require sensitive methods like next-generation flow cytometry (NGF) and next-generation sequencing (NGS) for detection. ⋯ Furthermore, it will likely help in tailoring treatment approaches, such as therapy escalation for high-risk patients or de-escalation for those achieving MRD negativity. Despite its prognostic value, challenges remain in standardizing MRD testing, ensuring its widespread availability, and addressing variability in results based on different detection methods. Future research aims to refine MRD-guided treatment and explore novel detection techniques, such as liquid biopsies, to improve patient monitoring in multiple myeloma.