Novel Approaches Outside the Setting of Immunotherapy for the Treatment of Multiple Myeloma: The Case of Melflufen, Venetoclax, and Selinexor

Although the survival rate of patients with multiple myeloma has significantly improved in the last years thanks to the introduction of various classes of new drugs, such as proteasome inhibitors, immunomodulatory agents, and monoclonal antibodies, the vast majority of these subjects relapse with a more aggressive disease due to the acquisition of further genetic alterations that may cause resistance to current salvage therapies. The treatment of these often “triple” (or even more) refractory patients remains challenging, and alternative approaches are required to overcome the onset of that resistance. Immunotherapies with novel monoclonal, drug-conjugated, or bi-specific antibodies, as well as the use of chimeric antigen receptor T cells, have been recently developed and are currently investigated. However, other non-immunologic therapeutic regimens based on melfluflen, venetoclax, or selinexor, three molecules with new mechanisms of action, have also shown promising results in the setting of relapsed/refractory myeloma. Here we report themost recent literature data regarding these three drugs, focusing on their efficacy and safety in multiple myelom

Sorption Thermodynamics of CO2, H2O, and CH3OH in a Glassy Polyetherimide: A Molecular Perspective

In this paper, the sorption thermodynamics of low-molecular-weight penetrants in a glassy polyetherimide, endowed with specific interactions, is addressed by combining an experimental approach based on vibrational spectroscopy with thermodynamics modeling. This modeling approach is based on the extension of equilibrium theories to the out-of-equilibrium glassy state. Specific interactions are accounted for in the framework of a compressible lattice fluid theory. In particular, the sorption of carbon dioxide, water, and methanol is illustrated, exploiting the wealth of information gathered at a molecular level from Fourier-transform infrared (FTIR) spectroscopy to tailor thermodynamics modeling. The investigated penetrants display a different interacting characteristic with respect to the polymer substrate, which reflects itself in the sorption thermodynamics. For the specific case of water, the outcomes from molecular dynamics simulations are compared with the results of the present analysis

Monoclonal B-cell lymphocytosis

Monoclonal B-cell lymphocytosis (MBL) is an asymptomatic hematologic condition defined by the presence of a small (<5 x 109/L) clonal B-cell population in the peripheral blood in the absence of lymph-node enlargement, cytopenias or autoimmune diseases. It is found in approximately 3-12% of normal persons depending on the accuracy of analytical techniques applied. According to the immunophenotypic profile of clonal B-cells, the majority of MBL cases (75%) are classified as chronic lymphocytic leukemia (CLL)-like. This form may progress into CLL at a rate of 1–2% per year. It is thought that CLL is always preceded by MBL. The remaining MBL cases are defined as atypical CLL-like (CD5+/CD20bright) and CD5- MBL. The MBL clone size is quite heterogenous. Accordingly, two forms of MBL are identified: i) high-count, or ‘clinical’ MBL, in which an evidence of lymphocytosis (<5 x 109/L clonal B-cells) is seen, and ii) a low-count MBL, in which a normal leukocyte count is found and that is identified only in population-screening studies. Both forms of MBL may carry the cytogenetic abnormalities that are the hallmark of CLL, including 13q-, 17p- and trisomy 12. Consistent with the indolent phenotype of this condition, genetic lesions, such as TP53, ATM, NOTCH1 and SF3B1 mutations, usually associated with high-risk CLL, are rarely seen. Overall, no prognostic indicator of evolution of MBL to overt CLL has been found at present time. However, taking into account this possibility, a clinical and lab monitoring (at least annually), is recommended

Time-resolved FTIR/FTNIR spectroscopy: powerful tools to investigate diffusion processes in polymeric films and membranes

AbstractThe application of time-resolved FTIR spectroscopy to investigate diffusion processes in polymers is described. Two thermosetting systems have been studied: a tetrafunctional epoxy resin cured with an aromatic diamine hardener, and a ternary formulation comprising the above components plus a bismaleimide co-monomer. Spectroscopic monitoring of water diffusion, both in the Mid and in the Near IR frequency ranges, yielded accurate and reproducible kinetic curves from which it was possible to evaluate the absolute parameters of diffusion (diffusivity and activation energy). These were found to compare favourably with the values obtained by conventional gravimetric methods. The molecular interactions between the penetrant molecules and the polymer networks were also investigated and it was shown that, in the system containing the bismaleimide component, the fraction of water molecules hydrogen-bonded to the network decreases significantly

Hypereosinophilia with a pinch of salt and pepper

Unavailable

Engineered plasmonic Thue-Morse nanostructures for LSPR detection of the pesticide Thiram

AbstractIn this paper, the size- and shape-dependent spectral characteristics of plasmonic nanostructures based on the Thue-Morse (ThMo) sequence are investigated in theory and experiment. We designed, fabricated, and characterized nine different Au nanopillars (NPs) lattices to evaluate their use as nanosensors based on localized surface plasmon resonances (LSPR). The extinction spectra and the bulk refractive index sensitivity (m) are compared to three selected shapes of the NPs (square, circular, and triangular) with different minimum interparticle distance. The maximum m of 275 nm/RIU is obtained for a ThMo pattern with square NPs. Finally, a detection limit of 260 pM (62 pg/ml) of Thiram pesticide has been achieved using an LSPR nanosensor based on an optimized ThMo pattern with triangular NPs employing a phase-sensitive setup to increase the figure-of-merit (FOM) of the sensor

SARS-CoV-2 infection in fully vaccinated patients with multiple myeloma

No abstract availabl

Inflammatory Cells in Diffuse Large B Cell Lymphoma

Diffuse large B cell lymphoma (DLBCL), known as the most common non-Hodgkin lymphoma (NHL) subtype, is characterized by high clinical and biological heterogeneity. The tumor microenvironment (TME), in which the tumor cells reside, is crucial in the regulation of tumor initiation, progression, and metastasis, but it also has profound effects on therapeutic efficacy. The role of immune cells during DLBCL development is complex and involves reciprocal interactions between tumor cells, adaptive and innate immune cells, their soluble mediators and structural components present in the tumor microenvironment. Different immune cells are recruited into the tumor microenvironment and exert distinct effects on tumor progression and therapeutic outcomes. In this review, we focused on the role of macrophages, Neutrophils, T cells, natural killer cells and dendritic cells in the DLBCL microenvironment and their implication as target for DLBCL treatment. These new therapies, carried out by the induction of adaptive immunity through vaccination or passive of immunologic effectors delivery, enhance the ability of the immune system to react against the tumor antigens inducing the destruction of tumor cells

Design and application of a novel PNA probe for the detection at single cell level of JAK2V617F mutation in Myeloproliferative Neoplasms

BACKGROUND: Mutation(s) of the JAK2 gene (V617F) has been described in a significant proportion of Philadelphia negative Myeloproliferative Neoplasms (MPN) patients and its detection is now a cornerstone in the diagnostic algorithm. METHODS: We developed a novel assay based on peptide nucleic acid (PNA) technology coupled to immuno-fluorescence microscopy (PNA-FISH) for the specific detection at a single cell level of JAK2-mutation thus improving both the diagnostic resolution and the study of clonal prevalence. RESULTS: Using this assay we found a percentage of mutated CD34+ cells ranging from 40% to 100% in Polycythemia Vera patients, from 15% to 80% in Essential Thrombocythemia and from 25% to 100% in Primary Myelofibrosis. This method allows to distinguish, with a high degree of specificity, at single cell level, between CD34+ progenitor stem cells harbouring the mutated or the wild type form of JAK2 in NPM patients. CONCLUSIONS: This method allows to identify multiple gene abnormalities which will be of paramount relevance to understand the pathophysiology and the evolution of any type of cancer