The median overall survival in multiple myeloma is rapidly approaching 10 years; however, in nearly a fifth of patients the prognosis remains poor. Therefore, the modern‐day management of myeloma patients should be individualized, with a more intense and continuous approach in these high‐risk patients. This includes first‐line treatment based on multi‐drug combinations employing the most effective drug combinations, upfront autologous stem cell transplantation (in eligible patients with tandem transplantation being a consideration), and maintenance based on proteasome inhibitor‐based combinations. This paper reviews the results of recent retrospective analyses and clinical trials, but also gives a glance into the future by presenting the ongoing trials.

We aimed to describe the clinical presentation, treatment, outcome and report on factors associated with mortality over a 90-day period in Clostridioides difficile infection (CDI). Descriptive, univariate, and multivariate regression analyses were performed on data collected in a retrospective case-control study conducted in nine hospitals from seven European countries. A total of 624 patients were included, of which 415 were deceased (cases) and 209 were still alive 90 days after a CDI diagnosis (controls). The most common antibiotics used previously in both groups were β-lactams; previous exposure to fluoroquinolones was significantly (p = 0.0004) greater in deceased patients. Multivariate logistic regression showed that the factors independently related with death during CDI were older age, inadequate CDI therapy, cachexia, malignancy, Charlson Index, long-term care, elevated white blood cell count (WBC), C-reactive protein (CRP), bacteraemia, complications, and cognitive impairment. In addition, older age, higher levels of WBC, neutrophil, CRP or creatinine, the presence of malignancy, cognitive impairment, and complications were strongly correlated with shortening the time from CDI diagnosis to death. CDI prevention should be primarily focused on hospitalised elderly people receiving antibiotics. WBC, neutrophil count, CRP, creatinine, albumin and lactate levels should be tested in every hospitalised patient treated for CDI to assess the risk of a fatal outcome.

The t(14;16) translocation, found in 3%-5% of newly diagnosed (ND) multiple myeloma (MM), has been associated with adverse outcomes. However, the studies establishing the characteristics of t(14;16) included solely small cohorts. The goal of the current international, multicenter (n = 25 centers), retrospective study was to describe the char-

It is unclear whether thrombus location in pulmonary arteries is associated with particular clot characteristics. We assessed 156 patients following either central or peripheral pulmonary embolism (PE). Plasma clot lysis time, the rate of D-dimer release from plasma clots (D-Drate) with the maximum D-dimer concentration achieved (D-Dmax), as well as fibrin formation on turbidimetry, plasma clot permeation, thrombin generation, and fibrinolytic parameters were measured 3–6 months after PE. Patients following central PE (n = 108, 69.3%) were more likely smokers (38.9% vs 18.8%; p = 0.01), less likely carriers of factor XIII Val34Leu allele (40.7% vs 62.5%, p = 0.01), exhibited 16.7% higher D-Drate and 12.7% higher tissue plasminogen activator antigen (tPA:Ag) compared with peripheral PE (p = 0.02 and p < 0.0001, respectively). Saddle PE patients (n = 31, 19.9%) had 11.1% higher D-Drate and 7.3% higher D-Dmax compared with central PE (both p < 0.05). Twenty-three recurrent PE episodes, including 15 central episodes, during a median follow-up of 52.5 months were recorded. Plasma D-dimer and tPA:Ag were independent predictors for central recurrent PE, whereas D-Drate and peak thrombin predicted peripheral recurrent PE. Plasma clots degradation is faster in patients following central PE compared with peripheral PE and fibrinolysis markers might help to predict a type of recurrent PE.

Multiple myeloma (MM) is an incurable haematological malignancy affecting approximately 7:100,000 people. Monoclonal gammopathy of undetermined significance (MGUS) and 'smouldering' MM precede symptomatic MM. Cytogenetics in MM is the most powerful prognostication tool incorporated into different classifications, including the Revised International Staging System (R-ISS) and the Mayo Clinic Risk Stratification for Multiple Myeloma (mSMART). Methods commonly used to test for cytogenetic aberrations include conventional karyotyping and fluorescence in situ hybridisation (FISH), although the difficulty of obtaining metaphases in plasma cells results in low yields.Therefore, new genomic tools are essential to explore the complex landscape of genetic alterations in MM. These include next generation sequencing, a highly sensitive method to monitor minimal residual disease. The serial evolution of MGUS to MM is accompanied by a range of heterogenous genetic abnormalities, divided into primary (involving mostly chromosome 14 translocations and trisomies) and secondary genetic aberration events (involving mostly 17p, 1p, 13q deletions, 1q gain, or MYC translocations). Based on the primary genetic aberration results, strong prognostic features of MM have been identified with distinct clinical characteristics. High risk aberrations include 17p deletion, t(4;14), t(14;16), t(14;20) and chromosome 1 abnormalities. The incorporation of novel drugs and maintenance strategies in conjunction with autologous stem cell transplantation partially overcome the adverse effect of some of these genetic aberrations. Nonetheless, survival remains worse in this group compared to standard risk patients. Clinical decisions regarding treatment should be based on the cytogenetic results. The establishment of individualised and mutation--targeted therapies are of the greatest importance in future studies.

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Background: Hematogenous extramedullary multiple myeloma (HEMM), though rare, is mainly observed in MM patients at relapse. The current study assesses the characteristics and outcomes of patients with MM who develop HEMM in the novel agent era. Methods: Consecutive patients, treated in 16 participating centers and diagnosed with HEMM, were included. Patient characteristics at diagnosis and at HEMM presentation, treatment regimens, response to therapy, response duration and survival were recorded. Factors predicting time to HEMM and survival from HEMM diagnosis were analyzed. Results: 127 patients were included. Median age at MM diagnosis was 63 years (31-94). 50% of patients had IgG MM, 26% had IgA, 23% had light chain, and 1% had other MM types. 44% had ISS 3 and 57% presented with plasmacytomas. 30% presented with high-risk cytogenetics: 19% with t(4;14),11% had 17p deletion. CD56 was expressed in 72% of cases and CD20 in 16%. 55% of the patients were treated for MM with PI, 55% with IMIDs, 62% with chemotherapy and 59% underwent autologous stem cell transplantation (ASCT) prior to HEMM. The median time to the development of HEMM was 2.8 years (95% CI 2.2-3.6). B2M levels (HR 1.04, 95% CI 1.00-1.07, p=0.03), del17p (HR 3.3, 95% CI 1.6-7.1, p=0.002) and plasmacytomas at MM diagnosis (HR 1.6, 95% CI 1.1-2.4, p=0.01) were associated with a shorter duration from diagnosis to HEMM, while upfront ASCT was associated with a longer period to the development of HEMM disease (HR 0.6, 95% CI 0.4-0.9, p=0.01). 47 patients (38%) patients had no concomitant plasmacytomas at HEMM diagnosis. 33% of patients had ≥2 HEMM sites, in 53% HEMM lesion was ≥5 cm, 20% had non-secretory disease at HEMM, and 59% had an increased LDH. 61% received at least 2 lines for MM prior to HEMM. First treatment for HEMM included PIs in 50%, IMIDs in 39%, MoAbs in 10% and chemotherapy in 53%. Overall response rate (ORR) was 49% and 51% failed to respond to first treatment for HEMM. IMIDs were associated with higher odds for ORR (OR 2.2, 95% CI 1.02-4.7, p=0.04). Median survival from MM diagnosis and from HEMM diagnosis were 4.3 (CI 95% 3-5.5) and 0.5 (CI 95% 0.4-0.6) years, respectively. 5-year OS from HEMM diagnosis was 6% (1-15%)(Figure 1A). Increased LDH level at the time HEMM (HR=2.2, 95% CI 1.3-3.8, p=0.002, Figure 1B), FISH positive for t(4;14) (HR=2.3, 95% CI 1.2-4.2, p=0.01)(Figure 1C), t(14;16) (HR=5.6, 95% CI 1.3-25, p=0.02)(Figure 1D), as well as ≤3 years between MM diagnosis and HEMM (HR=1.6, 95% CI 1.04-2.4, p=0.03(Figure 1E)), were found to be associated with a significantly shorter survival from HEMM diagnosis. The achievement of CR or VGPR to treatment administered for HEMM therapy were both associated with improved OS (HR=0.2, 95% CI 0.1-0.3, p<0.001 and HR=0.5, 95% CI 0.3-0.9, p=0.02, respectively) (Figure 1F). No specific treatment was found to be associated with improved survival in patients that develop HEMM. Conclusion: In MM patients who develop HEMM, the median time from MM to HEMM diagnosis is 2.8 years. Despite the improvement in MM therapy over the last decades, patients with HEMM diagnosis have a dismal outcome. OS is significantly shorter in patients with high-risk cytogenetic abnormalities, increased LDH and time to HEMM <3 years. Further studies assessing best therapy in patients experiencing this complication are warranted. Figure 1. Figure 1. Disclosures Cohen: Neopharm Israel: Consultancy, Honoraria; Takeda: Consultancy, Honoraria, Research Funding; Amgen: Consultancy, Honoraria, Research Funding; Janssen: Honoraria, Research Funding; Medisson Israel: Consultancy, Honoraria, Research Funding. Garderet:Takeda: Consultancy; Celgene: Consultancy; Amgen: Consultancy. Niesvizky:Amgen Inc.: Consultancy, Research Funding; Janssen: Consultancy, Research Funding; Celgene: Consultancy, Research Funding; BMS: Consultancy, Research Funding; Takeda: Consultancy, Research Funding. Castillo:Pharmacyclics: Consultancy, Research Funding; Beigene: Consultancy, Research Funding; Millennium: Research Funding; Genentech: Consultancy; Janssen: Consultancy, Research Funding; Abbvie: Consultancy, Research Funding.

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