Presse Medicale最新文献

Almost half of the acute pulmonary embolism (PE) survivors suffer from long-term sequelae that limit quality of life and their reintegration in society. The post-PE syndrome involves a spectrum of complications ranging from life-threatening pulmonary hypertension to deconditioning and psychosocial issues. The follow-up of acute PE has been demonstrated to be rife with challenges including long diagnostic delays, inefficient use of healthcare resources and the ignorance of psychosocial complications such as depression and anxiety. The best way to monitor recovery of PE comprehensively and reproducibly is the application of patient-reported outcome measures (PROMs), including quality of life assessment. PROMs help to identify and guide diagnostic tests and therapeutic interventions as well as to monitor the impact of the latter. In our view, therefore, PROMs should be integrated as a fundamental part of routine PE follow-up.

POEMS syndrome (Polyneuropathy, Organomegaly, Endocrinopathy, Monoclonal Protein, Skin changes) is a syndrome that involves a monoclonal B-cell proliferation, most often plasmacytic, and a variable number of manifestations listed or not in the acronym. These manifestations include sclerotic bone lesions, plasmacytic Castleman disease, papillary edema, peripheral edema, ascites, thrombocytosis and/or polycythemia, venous and/or arterial thrombosis, and renal, pulmonary, and cardiac impairments ^[1]. Diagnosis is often delayed due to the rarity of this entity and its clinical polymorphism, which can mimic other neurological disorders. First-line treatment for patients without bone marrow involvement and with a limited number of bone lesions is radiation. Patients with diffuse bone lesions or bone marrow involvement should receive systemic treatment, ideally intensive treatment with autologous stem cell transplantation (ASCT) when possible. Lenalidomide and bortezomib appear to be very promising, showing very rapid efficacy on neuropathy. Early initiation of treatment, before the development of severe neurological damage, along with supportive care, especially physiotherapy, is crucial for optimal neurological recovery.

Monoclonal gammopathy of undetermined significance (MGUS) and smoldering multiple myeloma (SMM) are premalignant stages in the development of multiple myeloma (MM). Advances in detection, risk stratification, and therapeutic intervention have transformed our understanding of disease progression. Sensitive techniques like mass spectrometry have identified smaller monoclonal gammopathies, such as monoclonal gammopathy of indeterminate potential (MGIP), which may precede MGUS. Risk stratification models for MGUS and SMM, including the Mayo Clinic, PETHEMA, 2/20/20, IMWG, and PANGEA models, leverage tumor burden markers and cytogenetic abnormalities to predict prognosis. Genomic studies have revealed mutations, structural changes, and mutational signatures that predict progression. Immune microenvironmental alterations underscore the multifactorial nature of disease evolution, while epigenetics is emerging as a source of tumoral and microenvironmental changes. Therapies for high-risk SMM, including lenalidomide, daratumumab, and next-generation immunotherapies, demonstrate efficacy in delaying progression to MM but raise concerns regarding safety in asymptomatic patients. Future research must refine prognostic models, integrate genomic and immunophenotypic data, and establish consensus on optimal strategies for early intervention. This comprehensive review highlights the biological, clinical, and therapeutic advancements in MM and its precursors, emphasizing the importance of early risk assessment and targeted treatment to improve outcomes.

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. Over the past two decades, tremendous progress has been made in improving the outcome in this age group with novel therapeutics, including immunomodulatory drugs, proteasome inhibitors, and more recently anti-CD38 monoclonal antibodies, becoming an integral part of initial treatment. Further improvements are expected over the next decade with novel immunotherapy, including T-cell engagers and chimeric antigen receptor therapies. With additional novel treatments, assessment of patient frailty will become increasingly important in balancing the optimal treatment of patients. In this review, we focus on the treatment of elderly and frail older adults with MM. 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.

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.

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. While conventional radiography has traditionally been the mainstay of initial evaluation of patients suspected of having MM, the advent of more sensitive imaging techniques such as computed tomography (CT), magnetic resonance imaging (MRI), and positron emission tomography (PET) have taken its place in assessing patients. While either CT alone or as part of a PET/CT examination is the initial radiographic method of choice, MRI remains the gold-standard modality in assessing bone marrow involvement, especially in early disease stages. 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.

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. LCCN typically reveals the underlying myeloma and manifests with severe acute kidney injury, high serum FLC level (>500 mg/l) and predominant light chain proteinuria (urine albumin/creatinine ratio <10 %). Urgent therapy is required, based on vigorous fluid expansion, correction of precipitating factors and introduction of efficient anti-myeloma therapy which choice should consider renal elimination of each agent and patient frailty. Early and deep reduction in serum FLC level conditions renal recovery, warranting assessment of efficacy by serial serum FLC level monitoring. In newly diagnosed patients, the combination of bortezomib, high-dose dexamethasone and an anti-CD38 monoclonal antibody is commonly used. The benefit to risk balance of quadruplets incorporating cyclophosphamide or an immunodulatory agent requires to be evaluated in prospective studies. 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.

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. MRD negativity has been associated with improved progression-free survival (PFS) and overall survival (OS), making it a key marker in clinical trials. The clinical utility of MRD lies in its ability to predict outcomes, with sustained MRD negativity linked to prolonged survival. 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.

Multiple myeloma treatment has evolved significantly with the introduction of triplet and quadruplet regimens, notably incorporating anti-CD38 antibodies. While autologous stem cell transplantation remains a cornerstone of therapy, its role in the context of increasingly effective upfront treatments is debated. Current guidelines still recommend transplant for all eligible patients, especially those with high-risk features at diagnosis, despite concerns regarding the lack of overall survival benefits and the potential long-term toxicities associated with high-dose melphalan. Delaying transplantation until first relapse has been proposed, but this approach carries the risk of patients becoming ineligible for transplantation due to worsening health or disease progression. Consolidation therapy after transplant is not strongly endorsed in recent guidelines, and studies show mixed results regarding its efficacy. Some data suggests a progression-free survival advantage with post-ASCT consolidation; others found no significant differences in outcomes among various strategies. Nonetheless, tandem transplant may be beneficial for high-risk patients. Maintenance therapy, particularly with lenalidomide, has proven effective, offering substantial progression-free and overall survival benefits. While lenalidomide remains the standard, emerging data indicate that combinations with proteasome inhibitors or anti-CD38 antibodies could enhance outcomes, particularly in high-risk populations. As our understanding of myeloma biology deepens, tailoring treatment approaches based on risk profiles and response depth will be crucial for optimizing patient outcomes.