Presse Med
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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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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.
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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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Multiple myeloma (MM) is the second most common adult hematologic malignancy, characterized by clonal proliferation of malignant plasma cells mostly in the bone marrow. The presence of destructive changes of the mineralized bone is a hallmark feature of the condition and a sign of end-organ damage. Due to this, imaging plays an integral role in the diagnosis, prognostication, and treatment monitoring of patients undergoing therapy for MM as well as surveillance of patients with early-stage disease. ⋯ PET/CT also provides valuable information regarding assessment of response to therapy and extramedullary manifestations of the disease. There is however increasing evidence that functional MRI techniques, albeit limitedly available, might be superior to PET/CT for treatment monitoring. This review summarizes current knowledge on the use of different imaging techniques in monoclonal plasma cell disorders and discusses future developments in this area of research.