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

Survival in multiple myeloma and SARS-COV-2 infection through the COVID-19 pandemic: Results from the EPICOVIDEHA registry

COVID-19; SARS-CoV-2; Multiple myelomaCOVID-19; SARS-CoV-2; Mieloma múltipleCOVID-19; SARS-CoV-2; Mieloma múltiplePatients affected by multiple myeloma (MM) have an increased risk of severe acute respiratory syndrome coronavirus type 2 (SARS-CoV-2) infection and subsequent coronavirus (20)19 disease (COVID-19)-related death. The changing epidemiological and therapeutic scenarios suggest that there has been an improvement in severity and survival of COVID-19 during the different waves of the pandemic in the general population, but this has not been investigated yet in MM patients. Here we analyzed a large cohort of 1221 patients with MM and confirmed SARS-CoV-2 infection observed between February 2020, and August 2022, in the EPICOVIDEHA registry from 132 centers around the world. Median follow-up was 52 days for the entire cohort and 83 days for survivors. Three-hundred and three patients died (24%) and COVID-19 was the primary reason for death of around 89% of them. Overall survival (OS) was significantly higher in vaccinated patients with both stable and active MM versus unvaccinated, while only a trend favoring vaccinated patients was observed in subjects with responsive MM. Vaccinated patients with at least 2 doses showed a better OS than those with one or no vaccine dose. Overall, according to pandemic waves, mortality rate decreased over time from 34% to 10%. In multivariable analysis, age, renal failure, active disease, hospital, and intensive care unit admission, were independently associated with a higher number of deaths, while a neutrophil count above 0.5 × 109/L was found to be protective. This data suggests that MM patients remain at risk of SARS-CoV-2 infection even in the vaccination era, but their clinical outcome, in terms of OS, has progressively improved throughout the different viral phases of the pandemic.EPICOVIDEHA has received funds from Optics COMMIT (COVID-19 Unmet Medical Needs and Associated Research Extension) COVID-19 RFP program by GILEAD Science, United States (Project 2020–8223)

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

No abstract availabl