Publications by authors named "Valentina Maria Manieri"

Despite the introduction of several therapies in recent years, multiple myeloma (MM) remains a hematologic malignancy difficult to treat due to its extreme inter- and intra-patient heterogeneity. However, at the 2024 major international conferences, very significant data have emerged on new approaches that can improve outcomes even in high-risk or very advanced diseases. Up-front quadruplet combinations, including anti-CD38 monoclonal antibodies, proved to be the best therapy in terms of depth of response and long-term efficacy in both transplant-eligible and not-eligible patients with MRD assessment that could play a key role in determining the duration of therapy, avoiding unnecessary overtreatment.

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Background/objectives: Treatments for multiple myeloma (MM) have expanded in the last decade, and the overall survival (OS) of MM patients (pts) is in continuous improvement. With the availability of new treatments and the use of high-dose chemotherapy, followed by autologous hematopoietic stem cell transplantation (ASCT), the median OS of newly diagnosed MM (NDMM) pts is 6-8 years. To date, approximately 50% and 28% of MM patients are still alive at 5 years and 10 years.

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The outcome of multiple myeloma (MM) has significantly improved in the last few decades due to several factors such as new biological discoveries allowing to better stratify disease risk, development of more effective therapies and better management of side effects related to them. However, handling all these aspects requires an interdisciplinary approach involving multiple knowledge and collaboration of different specialists. The hematologist, faced with a patient with MM, must not only choose a treatment according to patient and disease characteristics but must also know when therapy needs to be started and how to monitor it during and after treatment.

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Article Synopsis
  • Amyloid Light Chain (AL) Amyloidosis is a rare disorder where misfolded proteins form insoluble fibrils that can accumulate in different organs, leading to serious health issues and potential fatality.
  • The heart is the most commonly affected organ, and its involvement is often linked to worse outcomes, while the kidneys and liver can also be impacted, showcasing AL Amyloidosis as a multisystem disease.
  • Budd-Chiari syndrome (BCS), a rare liver condition caused by blocked hepatic veins, can occasionally be linked to AL Amyloidosis due to amyloid protein buildup in the liver, presenting an unusual clinical scenario.
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  • New therapies for multiple myeloma, like monoclonal antibodies daratumumab and isatuximab, have significantly improved patient outcomes, but more patients are becoming resistant to treatments earlier in their disease.
  • The rise of triple- or multi-refractory multiple myeloma (MM) highlights a significant medical need, complicating treatment options for these patients.
  • Recent advancements in immunotherapy, such as conjugated and bispecific antibodies and CAR T cells, show potential but come with challenges in patient selection and therapy sequencing, prompting ongoing research and clinical trials.
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  • Multiple Myeloma (MM) is challenging to treat due to its biological diversity, leading to varying patient outcomes; advancements in molecular methods are improving prognosis.
  • In newly diagnosed, transplant-eligible patients, the use of monoclonal antibodies like daratumumab enhances survival rates but remains less effective for those with high-risk features or minimal residual disease.
  • Ongoing research into cytogenetic risk and MRD-driven therapies, along with treatment strategies for non-transplant patients, aims to address the poor outcomes for refractory cases and improve overall management of MM.
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The introduction of high-dose therapy in the 1990s as well as the development of drugs such as thalidomide, lenalidomide, and bortezomib in the 2000s led to an impressive improvement in outcome of patients with multiple myeloma (MM) eligible for autologous stem cell transplantation (ASCT). Clinical trials conducted in the first ten years of the twenty-first century established as standard therapy for these patients a therapeutic approach including induction, single or double ASCT, consolidation, and maintenance therapy. More recently, incorporating second-generation proteasome inhibitors carfilzomib and monoclonal antibody daratumumab into each phase of treatment significantly improved the efficacy of ASCT in terms of measurable residual disease (MRD) negativity, Progression Free Survival (PFS), and Overall Survival (OS).

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