Predictors of unsustained measurable residual disease negativity in patients with multiple myeloma.

ABSTRACT: The prognostic impact of achieving and in particular maintaining measurable residual disease (MRD) negativity in multiple myeloma is now established; therefore, identifying among MRD-negative patients the ones at higher risk of losing MRD negativity is of importance. We analyzed predictors of unsustained MRD negativity in patients enrolled in the FORTE trial (NCT02203643). MRD was performed by multiparameter flow cytometry (sensitivity of 10-5) at premaintenance and every 6 months thereafter. The cumulative incidence (CI) of MRD resurgence and/or progression was analyzed in MRD-negative patients. A total of 306 of 474 (65%) MRD-negative patients were analyzed. After a median follow-up of 50.4 months from MRD negativity, 185 of 306 (60%) patients were still MRD negative and progression free, 118 (39%) lost their MRD-negative status, and 3 patients (1%) died without progression. Amp1q vs normal (4-year CI, 63% vs 34), ≥2 concomitant high-risk cytogenetic abnormalities vs 0 (4-year CI, 59% vs 33%), circulating tumor cells at baseline (high vs low at 4-year CI, 62% vs 32%), and time-to-reach MRD negativity postconsolidation vs preconsolidation (4-year CI, 46% vs 35%) were associated with a higher risk of unsustained MRD negativity in a multivariate Fine-Gray model. During the first 2 years of maintenance, patients receiving carfilzomib-lenalidomide vs lenalidomide alone had a lower risk of unsustained MRD negativity (4-year CI, 20% vs 33%).

Early Diffusion of SARS-CoV-2 Infection in the Inner Area of the Italian Sardinia Island.

BACKGROUND: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has been responsible for the coronavirus disease 2019 (COVID-19) pandemic, which started as a severe pneumonia outbreak in Wuhan, China, in December 2019. Italy has been the first European country affected by the pandemic, registering a total of 300,363 cases and 35,741 deaths until September 24, 2020. The geographical distribution of SARS-CoV-2 in Italy during early 2020 has not been homogeneous, including regions severely affected as well as administrative areas being only slightly interested by the infection. Among the latter, Sardinia represents one of the lowest incidence areas likely due to its insular nature. METHODS: Next-generation sequencing of a small number of complete viral genomes from clinical samples and their virologic and phylogenetic characterization was performed. RESULTS: We provide a first overview of the SARS-CoV-2 genomic diversity in Sardinia in the early phase of the March-May 2020 pandemic based on viral genomes isolated in the most inner regional hospital of the island. Our analysis revealed a remarkable genetic diversity in local SARS-CoV-2 viral genomes, showing the presence of at least four different clusters that can be distinguished by specific amino acid substitutions. Based on epidemiological information, these sequences can be linked to at least eight different clusters of infection, four of which likely originates from imported cases. In addition, the presence of amino acid substitutions that were not previously reported in Italian patients has been observed, asking for further investigations in a wider population to assess their prevalence and dynamics of emergence during the pandemic. CONCLUSION: The present study provides a snapshot of the initial phases of the SARS-CoV-2 infection in inner area of the Sardinia Island, showing an unexpected genomic diversity.

Methylation analysis of the phosphates and tensin homologue on chromosome 10 gene (PTEN) in multiple myeloma.

BACKGROUND: Aberrant DNA methylation of promoter region CpG islands is an alternative mechanism that leads to genetic defects in the inactivation of tumor suppressor genes during myelomagenesis. The aim of this study was to examine the promoter methylation status of the phosphates and tensin homologue on chromosome 10 (PTEN) gene in a cohort of multiple myeloma patients. FINDINGS: The PTEN gene was hypermethylated in 7 out of 58 (12%) primary myeloma samples. The correlation between functional inactivation and PTEN mRNA levels was not statistically significant. The multiple myeloma subgroup with an aberrant PTEN status had a prevalence of the component IgG, Salmon Durie stage I, lower lactate dehydrogenase levels, intermediate-standard cytogenetic risk and longer overall survival with the respect to the unmethylated subgroup. CONCLUSIONS: This is the first report demonstrating the presence of PTEN promoter hypermethylation in multiple myeloma.