The Modern Age of Monoclonal Antibodies: The Revolution of Daratumumab

CD38 is a transmembrane glycoprotein expressed on the surface of different cell lines with several functions (receptor, adhesion molecule, ectoenzyme). Based on its high expression in multiple myeloma cells, CD38 is one of the main molecules used in the target therapy age. Daratumumab is the first fully human monoclonal antibody tested in clinical trials, showing efficacy in relapsed/refractory multiple myeloma patients, especially in combination with immunomodulants and/or proteasome inhibitors. The synergic effect concerns multiple myeloma cells as well as the microenvironment (NK cells, macrophage, regulatory B/T cells and CD8+ effector cells). Therefore, the anti-multiple myeloma activity of Daratumumab greatly depends on the immune system: this is the reason why several ongoing clinical trial are testing its efficacy in the naïve patients, with a more effective immune system

Scenarios of Electromobility. Cross ferilisation and Dissemination of Best Practices and Researches within EU Policies Webinar proceedings

La pubblicazione riporta gli esiti del webinar incentrato sull'user center design dei veicoli elettrici, delle loro infrastrutture di ricarica e sulle sperimentazioni dei veicoli elettrici leggeri nei sistemi di trasporto urbano di Torino e Venaria Reale (IT), Villach (Austria) e Calvià (Spagna). La pubblicazione e il seminario sono parte del progetto STEVE, finanziato dal programma europeo Horizon2020, e incentrato sulla sperimentazione di modelli di mobilità elettrica leggera nelle aree urbane. Il progetto ha coinvolto città, piccole e medie imprese e università di sette paesi europei. Urban Lab ha collaborato con la Città di Torino a delineare le raccomandazioni rivolte ai decision makers in materia di pianificazione della mobilità urbana, emerse dai risultati dei tre anni di progetto

Race for the Cure: From the Oldest to the Newest Monoclonal Antibodies for Multiple Myeloma Treatment

Multiple myeloma is characterized by a wide clinical heterogeneity due to an intricate network of interactions between bone marrow-resident clonal plasma cells and the microenvironment. Over the last years, dramatic improvement in the understanding of these pathways led to the introduction of novel drugs with immune-mediated mechanisms of action. Some of these compounds, such as the anti-cd38 daratumumab and isatuximab, the anti-slamf-7 elotuzumab, and the antibody-drug conjugate belantamab-mafodotin, have been tested in large clinical trials and have now fully entered the real-life management. The bispecific T-cell engagers are under investigation with promising results, and other satisfactory data is expected from the application of nanotechnologies. The perfect timing to introduce these drugs in the sequence of treatment and their adverse events represent new challenges to be addressed, and further experience is required to improve their use

The unclear role of VEGF in POEMS syndrome: therapeutic implications of neoangiogenesis in a rare plasma cell disorder

POEMS syndrome is a rare paraneoplastic disorder due to an underlying clone of aberrant plasma cells. The name POEMS is an acronym for some of the major disease manifestations, namely polyneuropathy, organomegaly, endocrinopathy, presence of monoclonal component, and skin changes. The clinical presentation can be various and could lead to delayed diagnosis and treatment. Little is known about the pathogenic mechanism, although the neoangiogenesis due to overproduction of vascular endothelial growth factor (VEGF) by plasma cells seems to play a key role. The latest evidence suggests that the blood concentration of this cytokine correlates with the activity of the syndrome: VEGF could then be used as a therapeutic target and a marker to monitor response. Several case reports have shown the efficacy of this approach, but extended studies are required to better define the use of anti-VEGF in patients affected by POEMS syndrome

Azacitidine to consolidate and deepen the therapeutic response achieved by intensive induction treatment in a young patient affected by NPM1mut-AML who has become ineligible for high-dose consolidation

Acute myeloid leukemia (AML) is the most common leukemia in adults. In spite of the most recent discoveries about the molecular landscape of this disease, the treatment of elderly and unfit young patients continues to be a great challenge. The hypomethylating agents (HMA) still represent an effective therapeutic option for these categories, especially for the low-risk subgroups. We report the case of a young patient with NPM1mut-AML who underwent a first cycle of intensive induction treatment, achieving a complete remission, but suffered from a serious life-threatening neurologic toxicity. Due to the ineligibility to further lines of intensive chemotherapy, we decided to consolidate the response with azacitidine, administered according to the regular schedule. The minimal residual disease (MRD), monitored through the NPM1 mutation at diagnosis, progressively decreased and became undetectable after 36 cycles of hypomethylating therapy. After 1 year from discontinuation of azacitidine, MRD remains undetectable. Therefore, HMA might still represent a feasible and effective option for patients with low-risk AML, especially when the standard chemotherapy is not indicated, or as maintenance therapy in nontransplantable patients

Direct Oral Anticoagulants In Patients With Hematologic Malignancies

The anticoagulant treatment for patients with hematologic malignancies is low molecular weight heparin (LMWH), considered the safest in this particular patients setting. Although direct oral anticoagulants (DOACs) have proven their efficacy and safety in patients with cancer, their use can be challenging in patients with hematologic malignancies due to the peculiarity of these neoplasms: high thrombotic risk, possible onset of thrombocytopenia and concomitant anticancer therapies. The aim of our study was to evaluate the efficacy and safety of DOACs for venous thromboembolism or atrial fibrillation in patients with hematologic malignancies and plasmatic DOACs level during anticancer therapy and at time of bleeding or thrombotic complications. We evaluated patients with hematologic malignancies treated with DOACs for venous thromboembolism or atrial fibrillation; therapy was maintained until the platelet count was ≥50x109 /L. In case of concomitant anticancer treatment and hemorrhagic or thrombotic events, we checked DOACs plasma levels (trough and peak). The patients evaluated were 135:104/135 were on anticancer therapy. We did not observe either thrombotic or major hemorrhagic adverse events. Minor bleedings occurred in 10 patients and clinical relevant non major (CRNM) in 2 patients. There was a statistically significant correlation between bleedings and myelodysplastic syndrome. DOACs resulted effective and safe in patients with hematologic malignancies. DOACs plasma level can be helpful in suggesting an early dose adjustment to prevent hemorrhagic adverse event in patients on concomitant anticancer therapy. Larger prospective studies including hematologic patients are warranted to confirm the safety and efficacy of DOACs. This article is protected by copyright. All rights reserved

Do age, fitness and concomitant medications influence management and outcomes of CLL patients treated with ibrutinib?

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