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Simple Summary: Daratumumab (DARA) plus bortezomib, thalidomide, and dexamethasone (D-VTd) represent the standard of induction care in Europe for autologous stem cell transplantation (auto-SCT)-eligible, newly diagnosed multiple myeloma (NDMM) patients. This study aimed to investigate the possible impact of D-VTd induction therapy on hematopoietic engraftment after auto-SCT. Our findings indicate that patients treated with D-VTd experienced longer neutrophil and platelet engraftment times than those treated with VTd. Additionally, D-VTd treatment was associated with a higher incidence of febrile neutropenia and grade 2 or higher diarrhea. However, no significant differences were observed in the median number of days to discharge. The conclusion we can draw from our real-life study is that a four-drug induction therapy containing DARA does not impact transplant safety outcomes. Background: This real-life study aimed to investigate the possible impact of D-VTd induction therapy on hematopoietic engraftment after autologous stem cell transplantation (auto-SCT). Methods: Sixty consecutive NDMM patients received four cycles of induction therapy with D-VTd. The conditioning regimen consisted of melphalan 200 mg/m2. These patients were compared with a historical control group of 80 patients who received four cycles of VTd as induction therapy. Results: The median days to reach neutrophil and platelet engraftment significantly differed between patients treated with D-VTd (11 and 13 days, respectively) and VTd (10 and 12 days). Univariate Cox analyses show that patients treated with D-VTd had a hazard ratio of neutrophil engraftment that was 42% significantly lower than those in the VTd arm (HR: 0.58, p = 0.002), and a multivariate model confirmed this result. Patients treated with D-VTd developed FN more frequently. Univariate and multivariate logistic regressions revealed an association between D-VTd and FN. Delayed engraftment did not correlate with more extended hospitalization. No patients died in the first six months after transplantation. Conclusions: Our real-life study showed that a four-drug induction therapy containing DARA does not impact transplant safety outcomes. [ABSTRACT FROM AUTHOR]

Patients with multiple myeloma (MM) have an increased risk of sepsis due to underlying disease- and treatment-related immunosuppression. However, data on sepsis incidence, causative pathogens, and impact on outcomes in newly diagnosed MM (NDMM) are limited. We conducted a retrospective observational study of 92 NDMM patients who developed sepsis between 2022 and 2023 at a tertiary care center in Italy. Patient characteristics, sepsis criteria [Quick Sequential Organ Failure Assessment, Systemic Inflammatory Response Syndrome (SIRS)], microbiology results, and associations with progression-free survival (PFS) were analyzed. In this cohort of 92 critically-ill patients, pathogenic organisms were identified via microbiological culture in 74 cases. However, among the remaining 18 culture-negative patients, 9 exhibited a SIRS score of 2 and another 9 had a SIRS score of 4, suggestive of a clinical presentation consistent with sepsis despite negative cultures. Common comorbidities included renal failure (60%), anemia (71%), and bone disease (83%). Gram-negative (28%) and Gram-positive (23%) bacteria were frequent causative organisms, along with fungi (20%). Cox Univariate analyses for PFS showed statically significant HR in patients with albumin ≥ 3.5 vs < 3.5 (HR = 5.04, p < 0.001), Karnofsky performance status ≥ 80 vs < 80 (HR = 2.01, p = 0.002), and early-stage vs late-stage disease by International Staging System (HR = 4.76 and HR = 12.52, both p < 0.001) and Revised International Staging System (R-ISS III vs R-ISS I, HR = 7.38, p < 0.001). Sepsis is common in NDMM and associated with poor outcomes. Risk stratification incorporating sepsis severity, comorbidities, and disease stage may help guide preventive strategies and optimize MM management. [ABSTRACT FROM AUTHOR]

Objective: As multiple myeloma (MM) therapies advance, understanding patients', caregivers', and physicians' perspectives on, and satisfaction with, available treatment options and their impact on quality of life (QoL), is important. Methods: EASEMENT is a real‐world, observational, cross‐sectional study conducted in 19 sites within the UK, Canada, and Italy using retrospective chart reviews and surveys. Enrolled patients had clinical history available since diagnosis and had received ≥1 cycle of their current line of therapy. Primary objectives were to describe patient/caregiver QoL (EQ‐5D‐5L questionnaire), patient preference for oral/injectable therapies (single discrete‐choice question), and patient satisfaction (TSQM‐9 questionnaire). Results: Between October 2018 and March 2020, 399 patients were enrolled (n = 192 newly diagnosed multiple myeloma [NDMM], n = 206 relapsed/refractory multiple myeloma [RRMM], n = 1 missing). Among NDMM and RRMM patients, 78%/22% and 42%/58% were receiving injectables/orals, respectively. Both NDMM and RRMM patients significantly preferred orals versus injectables (p <.0001). No significant differences were reported in treatment satisfaction or QoL, but treatment convenience favoured orals over injectables with near significance (p =.053). Conclusion: MM patients perceived greater convenience and preference for orals versus injectables. Oral treatments are useful for patients who cannot or prefer not to travel to clinics, or cannot perform self‐injection within the community. [ABSTRACT FROM AUTHOR]

Introduction: Ixazomib, lenalidomide, and dexamethasone (IRd) have been approved for the treatment of relapsed/refractory multiple myeloma (RRMM) based on the results of the TOURMALINE‐MM1. Objectives and Methods: We conducted a retrospective–prospective analysis of 106 RRMM patients (pts) treated with IRd in 21 centers in Northern Italy, with the aim to evaluate the efficacy and safety of IRd in real life. Results: At IRd initiation, 34% of pts were aged ≥75 (median 72.5), 8.5% had an ECOG performance status ≥2, 54.7% of evaluable pts carried high‐risk cytogenetic abnormalities [del17p and/or t(4;14) and/or t(14;16) and/or 1 g gain/amp], 60.2% had received ≥2 prior lines of therapy (pLoT), 57.5% were lenalidomide (Len)‐exposed (including both Len‐sensitive and Len‐refractory pts), and 22% were Len‐refractory. Main G ≥3 adverse events (AEs) were thrombocytopenia (16%) and neutropenia (12.3%). G ≥3 non‐hematologic AEs included infections (9.4%) and GI toxicity (diarrhea 5.7%, hepatotoxicity 2.8%), VTE, skin rash, and peripheral neuropathy were mainly G1‐2. The overall response rate was 56.4% (≥VGPR 30%). With a median follow‐up of 38 m, median PFS (mPFS) was 16 m and the 1‐year OS rate was 73%. By subgroup analysis, an extended PFS was observed for pts achieving ≥VGPR (mPFS 21.2 m), time from diagnosis to IRd ≥5 years (26.2 m), 1 pLoT (34.4 m), Len‐naïve (NR), age ≥70 (20 m). In pts exposed to Len, non‐refractory in any prior line and immediately prior to IRd, mPFS was 16 and 18 m, respectively. An inferior PFS was seen in Len‐refractory pts (4.6 m). By multivariate analysis, independent predictors of PFS were age ≥70 (HR 0.6), time from diagnosis ≥5 years (HR 0.32), refractoriness to Len in any prior line (HR 3.33), and immediately prior (HR 4.31). Conclusion: IRd might be effective and safe in RRMM pts with an indolent disease, in early lines of treatment, and who proved Len‐sensitive, independent of age, and cytogenetic risk. [ABSTRACT FROM AUTHOR]

Purpose: Outcomes of multiple myeloma (MM) patients who are refractory to daratumumab are dismal and no standard of treatment exists for this patients' population. Here, we investigate the role of pomalidomide combinations in daratumumab-refractory MM patients. Methods: We performed a retrospective analysis of myeloma patients treated at four referral centers (three in Germany and one in Italy). Review chart identified 30 patients with relapsed and refractory myeloma, who progressed during treatment with daratumumab and were treated with pomalidomide-based combinations in the subsequent lines of therapy. Results: Responses improved from 37% with daratumumab to 53% with pomalidomide. Of seven patients with extramedullary MM (EMM), four achieved a clinical stabilization with pomalidomide, including one patient with a long-lasting complete response. Median progression-free survival and overall survival were 6 and 12 months, respectively. Pomalidomide combinations were well tolerated, no patient discontinued treatment due to adverse events. Conclusion: These data show that pomalidomide-based combinations can be an effective and safe salvage regimen for daratumumab-refractory patients, including those with EMM. [ABSTRACT FROM AUTHOR]

Simple Summary: We report an Italian multicentre study with the aim to reach a consensus based on the essential data to be included in the flow cytometry clinical report of patients with MM at diagnosis and after treatment. From the pre-analytical phase, through sample processing, data acquisition, analysis and evaluation of the potential limitations and pitfalls of the entire process, the study reaches a final conclusion shared by laboratories and clinicians according to the most up-to-date principles and recommendations. Flow cytometry is a highly sensitive and specific approach for discriminating between normal and clonal plasma cells in multiple myeloma. Uniform response criteria after treatment have been established by the International Myeloma Working Group and the EuroFlow Group; however, the way in which flow cytometry data are reported has suffered from no collaborative or multicentre efforts. This study, involving 8 expert laboratories and 12 clinical hematology units of the Lazio region in Italy, aims to produce a uniform and shared report among the various Centres. From the pre-analytical phase to sample processing, data acquisition, analysis, and evaluation of the potential limitations and pitfalls of the entire process, the study reaches a final conclusion shared by laboratories and clinicians according to the most updated principles and recommendations. The aim was to identify the necessary data to be included in the clinical report by using multiple-choice questionnaires at every single stage of the process. An agreement of more than 75% of the laboratories was considered mandatory for the data to be included in the report. By ensuring the operational autonomy of each laboratory, this study provides a clear report that limits subjective interpretations and highlights possible bias in the process, better supporting clinical decision-making. [ABSTRACT FROM AUTHOR]

Objectives: This non‐interventional observational study described the current standard‐of‐care for transplant‐eligible newly diagnosed multiple myeloma (TE‐NDMM) patients in France, Germany, Spain, and Italy, and recorded the evolution in regimen adoption in distinct elements of frontline treatment during 2017–2020/2021. Methods: Clinical information on ongoing (I) or previous (II) TE‐NDMM patients was extracted from the Cancerology database. Proportions of patients receiving regimens in each element and the evolution in regimen adoption were determined for the entire population and each country. Results: Most common induction regimens among I patients were VRd in France (75.3%) and Spain (44.1%), VTd in Italy (65.2%), and regimens other than VRd/VTd/VCd in Germany. Maintenance was ongoing/planned for 78.3%, 62.3%, 65.2%, and 61.4% patients in France, Germany, Spain, and Italy, respectively. Among II patients, VRd induction increased from 27.0% in 2017 to 65.7% in 2019 in France, remained relatively low in Spain and Germany, and not present in Italy. In Italy and Spain, VTd induction declined from 72.4% and 58.3% in 2017 to 52.8% and 17.3% in 2019, respectively. VCd induction in Germany declined from 85.2% in 2017 to 64.1% in 2019. Conclusion: The use of bortezomib triplets in induction varied markedly over time and between selected countries. [ABSTRACT FROM AUTHOR]

Background: We evaluated clinical features and risk factors for mortality in patients with haematological malignancies and COVID-19. Methods: Retrospective, case–control (1:3) study in hospitalized patients with COVID-19. Cases were patients with haematological malignancies and COVID-19, controls had COVID-19 without haematological malignancies. Patients were matched for sex, age and time of hospitalization. Results: Overall, 66 cases and 198 controls were included in the study. Cases had higher prior corticosteroid use, infection rates, thrombocytopenia and neutropenia and more likely received corticosteroids and antibiotics than controls. Cases had higher respiratory deterioration than controls (78.7% vs 65.5%, p = 0.04). Notably, 29% of cases developed respiratory worsening > 10 days after hospital admission, compared to only 5% in controls. Intensive Care Unit admission and mortality were higher in cases than in controls (27% vs 8%, p = 0.002, and 35% vs 10%, p < 0.001). At multivariable analysis, having haematological malignancy [OR4.76, p < 0.001], chronic corticosteroid therapy [OR3.65, p = 0.004], prior infections [OR57.7, p = 0.006], thrombocytopenia [OR3.03, p < 0.001] and neutropenia [OR31.1, p = 0.001], low albumin levels [OR3.1, p = 0.001] and ≥ 10 days from hospital admission to respiratory worsening [OR3.3, p = 0.002] were independently associated with mortality. In cases, neutropenia [OR3.1, p < 0.001], prior infections [OR7.7, p < 0.001], ≥ 10 days to respiratory worsening [OR4.1, p < 0.001], multiple myeloma [OR1.5, p = 0.044], the variation of the CT lung score during hospitalization [OR2.6, p = 0.006] and active treatment [OR 4.4, p < 0.001] all were associated with a worse outcome. Conclusion: An underlying haematological malignancy was associated with a worse clinical outcome in COVID-19 patients. A prolonged clinical monitoring is needed, since respiratory worsening may occur later during hospitalization. [ABSTRACT FROM AUTHOR]

Background: In combination with dexamethasone, lenalidomide is prescribed in the oral treatment of Multiple Myeloma for patients who have received at least one previous therapy. Objective: The objective of this study is to evaluate medication adherence to lenalidomide of Multiple Myeloma patients, as well as Progression Free Survival and Overall Survival one year from the beginning of the treatment. Setting: The study was carried out in Pescara Hospital, in Italy. All Multiple Myeloma patients who began lenalidomide therapy between January 1, 2012 and June 30, 2016 were included in our study. Methods: Adherence to treatment was calculated by using the ratio between the Received Daily Dose and the Prescribed Daily Dose. Effectiveness in real world has been evaluated as Progression Free Survival and Overall Survival one year from the beginning of the treatment. Main outcomes measure: We assessed medication adherence and effectiveness of lenalidomide in the treatment of Multiple Myeloma. Results: Adherence to the overall mean treatment was 0.73 ± 0.15, relative to 81 patients evaluated in our study. 32% of patients achieved an adherence equal to or greater than 80%. Real-life effectiveness in terms of Progression Free Survival and Overall Survival showed values of ​​53.75% and 88%, respectively, one year from the beginning of treatment. Conclusion: The analysis of adherence in Multiple Myeloma patients treated with lenalidomide one year from the beginning of therapy reveal a concerning lack of adherence. Moreover, the lack of correlation of the levels of adherence with patient-related variables shows that, in the case of Multiple Myeloma, adherence is not related to personal, social and environmental characteristics that may determine each patient's correct treatment implementation, but is directly influenced by disease evolution. [ABSTRACT FROM AUTHOR]

From April 2016, carfilzomib, in combination with lenalidomide and dexamethasone (KRD), became available for use in the daily practice in Italy for patients with relapsed or refractory multiple myeloma (RRMM). We performed a retrospective survey at 14 different institutions from Southern Italy in order to evaluate patient characteristics and treatment results from an unselected series of patients treated accordingly so far. One hundred and twenty-three consecutive patients were included, with a median of 2 previous lines of therapy (range 1–9) and a median age of 63 years (range 39–82). At the time of analysis, median number of courses administered is 11 (range 1–34), and all patients are evaluable for response. Overall response rate including complete remission, very good partial remission, and partial remission is 85%. After a median follow-up of 27 months, median overall and progression-free survival are 33 and 23 months, respectively. Sixty-three patients are alive and between them, 45 (37%) are in continuous remission. Sixty patients have died (49%), mainly from progressive disease. There were 6 treatment-related deaths (5% of the whole patient population). Overall, hematological and non-hematological toxicity were manageable, mostly on outpatient basis. Arterial hypertension has been observed in 43 cases (35%) but did not lead to treatment interruption. Our data demonstrate that in real life, KRD is highly effective and well tolerated in the majority of patients with RRMM. [ABSTRACT FROM AUTHOR]

High-dose chemotherapy followed by autologous stem cell transplantation (HD-ASCT) as well as the introduction of novel agents (NA) significantly improved survival for patients with multiple myeloma (MM). A total of 150 unselected newly diagnosed MM patients treated at our institution from 1998 to 2017 were retrospectively analyzed. Median age at diagnosis was 69 years (range 33-93 years) with a median follow-up of 48.6 months. The median overall survival (OS) for the entire cohort was 60.7 months (range 0.3-280.1). Patients who received frontline HD-ASCT (p < 0.01) or NA-based first-line treatment (p = 0.043) had a significantly better OS. According to the revised Myeloma Comorbidity Index (R-MCI), patients were defined as fit (36.5%), intermediate-fit (44.5%), or frail (19%) with a significant difference in OS between these categories (p < 0.01). Multivariate analysis revealed R-MCI as an independent prognostic factor for OS (p < 0.01). Presence of subclinical amyloid deposits (A+) was detected in 18 out of 66 patients (27.3%) and significantly correlated with a serum free light chain (sFLC) ratio ≥ 100 (p = 0.01) and bone marrow plasma cell infiltration > 60% (p = 0.04). Furthermore, patients with A+ had significantly worse OS compared with their counterparts (p = 0.048). Our results corroborate the efficacy of both early HD-ASCT and the use of new agents as initial therapy of MM patients in "real-world" daily clinical practice. The R-MCI is an easily applicable tool to stratify MM patients and may support treatment decisions. The prognostic value of subclinical amyloid deposition should be validated within prospective studies. [ABSTRACT FROM AUTHOR]

Background: Daratumumab is a humanized monoclonal antibody approved for the treatment of adult patients with newly diagnosed or relapsed/refractory multiple myeloma (RRMM). Subcutaneous (SC) formulation proved to be non-inferior in comparison with intravenous (IV) administration route. This study aimed at assessing the economic and time impact associated with the use of SC versus IV daratumumab in patients with RRMM from the perspective of the hematology center., Methods: This was a 5-month multicenter time-and-motion cross-sectional micro-costing study conducted in three Italian hematology centers among adult patients diagnosed with RRMM with ongoing treatment with IV or SC daratumumab. Measurements were performed by an ad hoc App., Results: Nineteen (20%) IV and 76 (80%) SC administration procedures were measured. Patients spent a mean of 4.85 ± 0.91 or 1.08 ± 0.56 h in the hematology center to receive IV or SC daratumumab, respectively. Healthcare professionals (HCPs) spent a mean of 49.38 ± 16.13 and 20.37 ± 7.88 min of active working time to manage IV and SC administrations, respectively. The infusion chair was occupied for a mean of 4.85 ± 0.91 and 0.99 ± 0.55 h during IV or SC administration, respectively. On average, considering the costs due to HCP and chair time, materials, and overhead costs, every IV and SC administration costed €80.33 and 34.90, respectively., Conclusions: In conclusion, as compared with IV administration, SC daratumumab was associated with 78%, 59%, 80% savings in terms of patient time, HCP active working time, and infusion chair, respectively, and 56.6% budget savings., (© 2023 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.)

Objectives: This study aimed to provide real‐world data on the characteristics and treatment of patients with multiple myeloma (MM) at the time of death. Methods: The study was a retrospective patient chart review across France, Germany, Italy, Spain and the UK during 2016, and included patients who had died in the 3 months before the index date. Results: Data from 786 patients were reviewed. At the time of death, 37% of patients were receiving active treatment, 12% were in a treatment‐free interval and 51% were receiving only supportive care. Death before and during active first‐line treatment was not uncommon (6% and 24% of patients, respectively) but these deaths were often not solely due to disease progression; factors such as renal failure and infection frequently played a role (in 30% and 20% of patients at first‐line, respectively). Most deaths at later lines were due to progressive disease. Cox model results suggested that early deaths were associated with advanced disease stage, high‐risk cytogenetics and poor response and relapse profiles. Conclusions: These real‐world data could be used to help develop strategies for improving survival in patients with MM and to support management tailored to the stage of disease. [ABSTRACT FROM AUTHOR]

Background: High-dose melphalan plus autologous stem-cell transplantation (ASCT) is the standard approach in transplant-eligible patients with newly diagnosed myeloma. Our aims were to compare consolidation with high-dose melphalan plus ASCT versus chemotherapy (cyclophosphamide and dexamethasone) plus lenalidomide, and maintenance with lenalidomide plus prednisone versus lenalidomide alone.Methods: We did an open-label, randomised, multicentre, phase 3 study at 59 centres in Australia, Czech Republic, and Italy. We enrolled transplant-eligible patients with newly diagnosed myeloma aged 65 years or younger. Patients received a common induction with four 28-day cycles of lenalidomide (25 mg, days 1-21) and dexamethasone (40 mg, days 1, 8, 15, and 22) and subsequent chemotherapy with cyclophosphamide (3 g/m(2)) followed by granulocyte colony-stimulating factor for stem-cell mobilisation and collection. Using a 2 × 2 partial factorial design, we randomised patients to consolidation with either chemotherapy plus lenalidomide (six cycles of cyclophosphamide [300 mg/m(2), days 1, 8, and 15], dexamethasone [40 mg, days 1, 8, 15, and 22], and lenalidomide [25 mg, days 1-21]) or two courses of high-dose melphalan (200 mg/m(2)) and ASCT. We also randomised patients to maintenance with lenalidomide (10 mg, days 1-21) plus prednisone (50 mg, every other day) or lenalidomide alone. A simple randomisation sequence was used to assign patients at enrolment into one of the four groups (1:1:1:1 ratio), but the treatment allocation was disclosed only when the patient reached the end of the induction and confirmed their eligibility for consolidation. Both the patient and the treating clinician did not know the consolidation and maintenance arm until that time. The primary endpoint was progression-free survival assessed by intention-to-treat. The trial is ongoing and some patients are still receiving maintenance. This study is registered at ClinicalTrials.gov, number NCT01091831.Findings: 389 patients were enrolled between July 6, 2009, and May 6, 2011, with 256 eligible for consolidation (127 high-dose melphalan and ASCT and 129 chemotherapy plus lenalidomide) and 223 eligible for maintenance (117 lenalidomide plus prednisone and 106 lenalidomide alone). Median follow-up was 52·0 months (IQR 30·4-57·6). Progression-free survival during consolidation was significantly shorter with chemotherapy plus lenalidomide compared with high-dose melphalan and ASCT (median 28·6 months [95% CI 20·6-36·7] vs 43·3 months [33·2-52·2]; hazard ratio [HR] for the first 24 months 2·51, 95% CI 1·60-3·94; p<0·0001). Progression-free survival did not differ between maintenance treatments (median 37·5 months [95% CI 27·8-not evaluable] with lenalidomide plus prednisone vs 28·5 months [22·5-46·5] with lenalidomide alone; HR 0·84, 95% CI 0·59-1·20; p=0·34). Fewer grade 3 or 4 adverse events were recorded with chemotherapy plus lenalidomide than with high-dose melphalan and ASCT; the most frequent were haematological (34 [26%] of 129 patients vs 107 [84%] of 127 patients), gastrointestinal (six [5%] vs 25 [20%]), and infection (seven [5%] vs 24 [19%]). Haematological serious adverse events were reported in two (2%) patients assigned chemotherapy plus lenalidomide and no patients allocated high-dose melphalan and ASCT. Non-haematological serious adverse events were reported in 13 (10%) patients assigned chemotherapy plus lenalidomide and nine (7%) allocated high-dose melphalan and ASCT. During maintenance, adverse events did not differ between groups. The most frequent grade 3 or 4 adverse events were neutropenia (nine [8%] of 117 patients assigned lenalidomide plus prednisone vs 14 [13%] of 106 allocated lenalidomide alone), infection (eight [8%] vs five [5%]), and systemic toxicities (seven [6%] vs two [2%]). Non-haematological serious adverse events were reported in 13 (11%) patients assigned lenalidomide plus prednisone versus ten (9%) allocated lenalidomide alone. Four patients died because of adverse events, three from infections (two during induction and one during consolidation) and one because of cardiac toxic effects.Interpretation: Consolidation with high-dose melphalan and ASCT remains the preferred option in transplant-eligible patients with multiple myeloma, despite a better toxicity profile with chemotherapy plus lenalidomide.Funding: Celgene. [ABSTRACT FROM AUTHOR]

Light-chain amyloidosis (AL) is considered a rare disease, although few studies have assessed its epidemiology. Therefore, we felt it appropriate to examine the regional incidence of new AL diagnosis at Careggi University Hospital, the only multidisciplinary regional referral centre for amyloidosis serving the Florence metropolitan area, in Italy. At our institution, AL diagnosis was performed by biopsy of abdominal fat pad or of another involved organ, showing amyloid deposits characterised as AL type by immunohistochemistry, optic/immunoelectron microscopy or proteomics [[1]]. [Extracted from the article]

Vertebral fractures occur in over 60% of newly diagnosed multiple myeloma ( MM) patients and can cause pain, disability and poor quality of life. Antimyeloma therapy can lead to symptoms improvement, but these effects can take time to be perceived. Application of radiotherapy prior to peripheral blood stem cells ( PBSC) mobilisation can impair stem cell collection. Percutaneous vertebroplasty has been proposed as a suitable option to rapidly relieve bone pain from vertebral fractures in MM patients, but, little is known about the effects of this procedure on subsequent PBSC mobilisation, collection and transplant. Eighteen patients (10 M/8 F, median age 64.5 years) with untreated MM and painful vertebral lesions underwent vertebroplasty prior to proceed to the planned transplant program at our Institution. Forty-one procedures were performed at C2- L5 levels, eight patients were treated at ≥2 levels. Ninety-five per cent of the cases obtained a complete or optimal pain control. All the patients successfully mobilised PBSC (median CD34+ cells = 10.8 × 106/kg) and underwent autologous PBSC transplant; both polymorphonucleates and platelets recovery averaged 11 days. Our data seem to suggest that percutaneous vertebroplasty is useful in newly diagnosed MM patients with painful vertebral fractures as it allows rapid and durable achievement of pain control, without interfering with further treatment. [ABSTRACT FROM AUTHOR]

Abstract: We analyzed the main modalities and clinical outcomes of the early discharge outpatient model in autologous stem cell transplantation (EDOM-ASCT) for multiple myeloma in Italy. EDOM-ASCT was employed in 382 patients, for a total of 522 procedures, between 1998 and 2012. Our study showed high homogeneity among centers in terms of inclusion criteria, supportive care, and in hospital readmission criteria. Overall, readmissions during the aplastic phase occurred in 98 of 522 transplantations (18.8%). The major extrahematological complication was neutropenic fever in 161 cases (30.8%), which required readmission in 76 cases. The incidence of severe World Health Organization grade 3 to 4 mucositis was 9.6%. By univariate analysis, fever, mucositis, altered renal function at diagnosis, second transplantation, and transplantation performed late in the course of the disease were significantly correlated with readmission, whereas fever, mucositis, altered renal function, and timing of transplantation remained the only independent predictors by multivariate analysis. Overall, transplantation-related mortality was 1.0%. No center effect was observed in this study (P = .36). The safety and low rate of readmission of the EDOM-ASCT in myeloma trial suggest that this strategy could be extended to other transplantation centers if a stringent patient selection and appropriate management are applied. [Copyright &y& Elsevier]

Background: In many regions of southern Italy, hepatitis C virus (HCV) infection represents a major health problem (with a prevalence rate between 6% and 13%). HCV is associated with different kinds of neoplasms such as non-Hodgkin lymphomas (NHL), and with auto-immune diseases (cryoglobulinemia), which develop after the virus has caused immune system alterations. Objectives: To provide updated information on trends in mortality in a major metropolitan area of southern Italy from NHL, multiple myeloma and Hodgkin disease we analyzed cancer mortality data from 1988 to 2009. Materials and Methods: Mortality data were extracted from National death certificates by age groups, gender, residence and cause of death by the Italian national institute of statistics (ISTAT). Age-standardized mortality rates (SMR) were computed applying the direct method and using the world standard population. To quantify the recent direction of temporal trends in older populations over time, truncated age-adjusted mortality rates were calculated for people aged 65 years and older. Cancer mortality trends were described using their estimated annual percent change (EAPC) and related 95% Confidence Interval (CI). Results: Statistically significant increasing EAPC was found among women for NHL (+2.0% / year), while statistically significant decrease was found among men and women for HD (-3.5% / year, -3.4% / year, respectively). No statistically significant EAPC was found for multiple myeloma. Conclusions: The association between viral hepatitis and NHL in the area of interest might provide some degree of explanation to this finding. Our data confirm that due to epidemic infection of HCV in the area of Naples, a high mortality for NHL persists, moreover the adoption of standard therapeutic protocols administered in full accordance with an evidence-based approach and current guidelines explain reduced mortality from Hodgkin lymphomas. [ABSTRACT FROM AUTHOR]

Abstract: To evaluate trends in allografting from unrelated donors, we conducted a study on 196 consecutive myeloma patients transplanted between 2000 and 2009 in Italy. Twenty-eight percent, 37%, and 35%, respectively, received myeloablative, reduced-intensity, and nonmyeloablative conditioning. In these 3 cohorts, 1-year and 5-year transplantation-related mortalities were 28.8% and 37.0%, 20.3% and 31.3%, and 25.0% and 30.3%, respectively (P = .745). Median overall survival (OS) and event-free survival from transplantation for the 3 cohorts were 29 and 10 months, 11 and 6 months, and 32 and 13 months, respectively (P = .039 and P = .049). Overall cumulative incidences of acute and chronic graft-versus-host-disease (GVHD) were 46.1% and 51.1%. By Cox multivariate analyses, chronic GVHD was significantly associated with longer OS (hazard ratio [HR], .51; P = .009), whereas the use of peripheral blood stem cells was borderline significant (HR, .55; P = .051). Better response posttransplantation was associated with longer event-free survival (HR, 2.13 to 4.25; P < .001). Acute GVHD was associated with poorer OS (HR, 2.53; P = .001). This analysis showed a strong association of acute and chronic GVHD and depth of response posttransplantation with clinical outcomes. Long-term disease control remains challenging regardless of the conditioning. In the light of these results, prospective trials may be designed to better define the role of allografting from unrelated donors in myeloma. [Copyright &y& Elsevier]

Abstract: Pollen from intestinal contents of mummies, backed by macrofloral analysis, provides important clues to diet, medicines, and season of death. Intestinal contents were recovered from the Piraino 1 mummy from the “Sepulcher of the Priests”, Piraino Mother Church, in the province of Messina, Sicily. Using standard palynological methods and pollen concentration technique, we quantified the numbers of pollen grains per gram of coprolite. The pollen spectrum was dominated by Polygalaceae, the Milkwort Family. Polygalaceae pollen is rarely found in archaeological sites. Based on comparison to published keys, we determined that the pollen came from a species of Polygala. Polygala contains species with medicinal value. We found nine other pollen types. Traces of Potamogeton (pondweed) was observed in preliminary scans. Multiple grains of Brassicaceae (mustard family), cereal (cultivated grains), Typha (cattail) and Cheno-am were found. Single grains of Castanea (chestnut), Fabaceae (bean family), Salix (willow), and Solanaceae (tomato family) were found. The preservation of the pollen was poor except for Polygala and the cereal pollen. Brassicaceae and Cheno-am have been part of the natural pollen spectrum in Sicily since ancient times. Cereal grains were consumed with prepared food. Importantly, background arboreal pollen was nearly absent. This indicates that Piraino 1 died during months of low pollination. The absence of olive pollen is important since this plant in Sicily reaches its maximum pollination in May and June and tapers off rapidly by mid-June. Therefore, absence of the key warm season airborne pollen type suggests a post-June death. Macrofossils, especially residue from grape pulp, indicates a death in September to November. His cause of death was likely a result of multiple myeloma. The methodological differences between archaeopalynology and forensic palynology are summarized. We suggest that the palynological methods presented here should be adopted for human remains analysis in forensic palynology. [Copyright &y& Elsevier]

The article presents a case study of several Italian Caucasian multiple myeloma patients who experienced adverse skin reactions to treatment with lenalidomide, noting the role of histocompatibility antigen (HLA) genes in the complications. Patients suffering from severe drug hypersensitivity were positive for HLA-DRB∗1501 and HLA-DQB1∗0602. Adverse reactions included urticaria, erythema multiforme, and Stevens-Johnson syndrome.

KOLEVA D., CORTELAZZO S., TOLDO C. & GARATTINI L. (2011) European Journal of Cancer Care, 330-336 Few economic evaluations are currently available on multiple myeloma (MM) and they address treatment-related rather than disease-related costs. We estimated resource utilisation and costs associated with MM in an Italian haematology department. This was a single-centre observational study which followed retrospectively for 2 years 90 patients with MM stages II-III. To investigate the association between costs and age as a prognostic factor for treatment eligibility, patients were classified in two age groups (under 65 or >65). The annual average cost per patient was very similar in the two subgroups. Drugs and hospitalisations were the largest cost components. Differences between the two age groups were significant only for drugs, hospital admissions and day hospital (DH) days. Autologous stem-cell transplantation (ASCT) accounted for more than 80% of the non-pharmacological therapy costs, being nearly double in the younger patients. Cost of elderly patients is comparable with that of younger ones who generally receive expensive procedures such as ASCT. The higher hospital costs of younger patients were counterbalanced by supportive pharmaceutical care and DH days for older patients, mainly in the group treated with new immunomodulatory agents. Further multi-centre studies on larger samples of patients are needed. [ABSTRACT FROM AUTHOR]

The article focuses on a study which evaluated the effectiveness and safety of the addition of bortezomib to thalidomide plus dexamethasone (TD) (VTD) against TD alone as induction therapy prior to double analogous stem-cell transplantation in multiple myeloma. Patients at the Grupo Italiano Malattie EMatologiche dell'Adulto (GIMEMA) Myeloma Network hospitals were selected. Results indicate that patients eligible for transplant, induction and consolidation therapy with VTD improved clinical outcomes compared to patients receiving only TD therapy.

To analyze the relationship between asbestos exposure and malignant lymphoma in a multicenter case–control study conducted in Germany and Italy according to a common core protocol. Male and female patients with malignant lymphoma ( n = 1,034) between 18 and 80 years of age were prospectively recruited in six study areas in Germany (Ludwigshafen/Upper Palatinate, Heidelberg/Rhine-Neckar-County, Würzburg/Lower Frankonia, Hamburg, Bielefeld/East Westphalia, and Munich) and in two study areas in Sardinia, Italy (Cagliari and Nuoro provinces). A total of 1,173 population control subjects were drawn from population registers. In a structured personal interview, we elicited a complete occupational history, including every occupational period that lasted at least 1 year. On the basis of job task-specific supplementary questionnaires, trained experts assessed the exposure to asbestos. As a measure of cumulative asbestos exposure on a time by intensity scale, fiber-years were calculated. 12 cases (1.2%) and 12 control subjects (1.0%) had a cumulative asbestos exposure of more than 2.6 fiber-years (highest exposure category according to the 90th percentile of exposed control subjects). Odds ratios (OR) and 95% confidence intervals (CI) were calculated using unconditional logistic regression analysis adjusted for age, sex and study region. Patients with specific lymphoma sub-entities were additionally compared with the entire control group. We observed no statistically significant association between cumulative asbestos exposure and the risk of any lymphoma subtype. An elevated risk was found for the association between exposure to more than 2.6 fiber-years and multiple myeloma (OR = 6.0; 95% CI 1.4–25.1); however, numbers were small ( n = 3 cases, all of them from Italy; n = 12 control subjects). Our study does not support an association between asbestos exposure and risk of malignant lymphoma. [ABSTRACT FROM AUTHOR]

The article presents a case study which examines the role of benzene exposure in causing leukemia and multiple myeloma (MM) in Italy. The study involves the assessment of patients' exposure at individual level to a range of chemicals. The authors claim that they found no association between exposure to any solvent and acute myeloid leukemia (AML). They also found elevated point estimates for the associations between medium/high benzene exposure and chronic lymphatic leukemia.

In the context of a population-based case-control study in Italy, the authors investigated the possible association between the personal use of hair dyes and non-Hodgkin's lymphoma (NHL), leukemia, multiple myeloma, and Hodgkin's disease. They collected all incident cases of hematolymphopoietic malignancies; the control group was formed with a random sample of the general population. Overall, the authors interviewed 2,737 research subjects and 1,779 control subjects. Among women, the authors found no association between ever using hair dyes and the risk of hematolymphopoietic malignancies. However, for permanent hair dyes, the authors observed a slightly increased risk of lymphocytic leukemia (odds ratio [OR] = 1.3; 95% confidence interval [CI] = 0.8-2.2) and of follicular subtypes of NHL (OR = 1.3; 95% CI = 0.8-2.0). Women who used black hair dye colors were at an increased risk of developing leukemia (OR = 1.9; 95% CI = 1.0-3.4), in particular chronic lymphocytic leukemia (OR = 3.0; 95% CI = 1.1-7.5). In spite of the lack of information on the timing and frequency of hair dye use and the imprecision of the ORs, associations were suggested between leukemia and permanent black hair dye use and follicular NHL and the use of permanent hair dyes. [ABSTRACT FROM AUTHOR]

Presents a study of newly-diagnosed multiple myeloma patients admitted to hospitals in northeast Italy from 1987-1992, to examine the course of the disease. Evidence of the poor prognosis of older patients; Improvement of the survival rates; Contribution of clinical trial participation to the improved results of therapy.

Objectives: To evaluate the relation between the exposure to specific pesticides in agricultural work and the risk of multiple myeloma (MM).Methods: A case-control study was conducted in the province of Forlì, Italy. Forty-six cases of MM (20 females, 26 males; mean age 64 years, range 40 to 74) identified through the Romagna Cancer Registry in the years 1987-90, and 230 age- and gender-matched controls from the general population were interviewed in-person using a structured questionnaire focused on exposure to pesticides and other occupational and nonoccupational variables.Results: Among nonoccupational factors, the education level and the altitude of the place of residence were related inversely to MM risk. First-degree familiarity for hematolymphopoietic neoplasias and previous herpes zoster diagnosis were associated positively with the disease. A nonsignificant increase in MM risk was observed among workers in agriculture as a whole (odds ratio [OR] = 1.31, 95 percent confidence interval [CI] = 0.62-2.74). An increased risk was associated specifically with the cultivation of apples and pears (OR = 1.75, CI = 1.05-2.91). As regards pesticide exposure, only the chlorinated insecticides were related to an increase in the risk of MM.Conclusions: This study suggests that agricultural work and exposure to pesticides have a role in the etiology of MM. [ABSTRACT FROM AUTHOR]

Objectives: Solitary plasmacytoma (SP) is characterized by a single mass of clonal plasma cells. Definitive RT can result in long-term local control of the SP. Due to the small number of patients and narrow range of doses, phase III randomized trials are lacking. The aim of this study is to further support the potential use of RT for the treatment of SP., Methods: Clinical data of all patients treated for SP at our Institution between 1992 and 2018 were reviewed. A total of 42 consecutive patients were analyzed., Results: The median follow-up was 84.8 months. Radiation dose did not differ significantly as a function of sex, type of SP (solitary bone plasmacytoma or as extramedullary plasmacytoma), tumor size; conversely differs significantly as a function of age (p = 0.04). The 5y-OS and 10y-OS were, respectively, 96 and 91%. Local recurrences developed in 21.4% of patients (9/42). 16 patients progressed to MM (38.1%). The 5y-progression to MM free survival (PMFS) and the 10y-PMFS were, respectively, 68.6 and 61.9%., Conclusions: Our data confirm that good results are achievable with RT to treat SP, but they don't allow defining a dose-effect correlation; therefore, it remains uncertain which is the most effective dose and whether lower doses can guarantee adequate disease control.

A letter to the editor in response to an article dealing with relapsed multiple myeloma in Great Britain before the introduction of novel agents which appeared in previous issue is presented.

Simple Summary: Multiple myeloma (MM) is associated with high morbidity and mortality and variable survival that requires early identification of high-risk patients in order to quickly adapt treatment. FDG-PET/CT is a promising technique for initial staging of symptomatic MM. The aim of our retrospective study was to asses the prognostic value of this technique at baseline in symptomatic MM patients included in two large European prospective studies. After harmonization of data by and ad-hoc approach called M-Combat, we confirmed the prognostic value of FDG-PET/CT in a population of 227 MM patients, by integrating a new prognostic biomarker named "bone SUVmax" (including the maximum intensity of fixation of focal lesions and bone marrow) which is strongly correlated with a poorer prognosis of MM patients. Prognostic patient stratification is currently based on laboratory tests and genomic abnormalities, but FDG-PET/CT is likely to be an important method of defining high-risk patients, and thus, to potentially better adapt future therapeutic management. Background: Multiple myeloma is a hematological neoplasm characterized by a clonal proliferation of malignant plasma cells in the bone marrow, and is associated with high morbidity and mortality and variable survival. Positron emission tomography combined with computed tomography using 18F-deoxyfluoroglucose (FDG-PET/CT) is a promising technique for initial staging of symptomatic multiple myeloma patients. The objective of this study was to assess the prognostic value of this technique at baseline in symptomatic multiple myeloma patients included in two large European prospective studies (French and Italian). Methods: We retrospectively performed a combined harmonized analysis of 227 newly diagnosed transplant eligible multiple myeloma patients from two separate phase III trials. All images were centrally reviewed and analyzed using visual criteria and maximal standardized uptake value. An ad-hoc approach (called modified Combat) was applied to harmonize the data and then remove the "country effect" in order to strengthen the reliability of the final conclusions. Results: Using a multivariate analysis including treatment arm, R-ISS score, presence of extra-medullary disease and bone SUVmax, only bone SUVmax (p = 0.016) was an independent prognosis factor with an OS threshold of 7.1. For PFS, treatment arm and presence of extra-medullary disease were both independent prognosis biomarkers (p = 0.022 and 0.006 respectively). Conclusions: Our results show that bone SUVmax is a simple and reliable biomarker to analyze FDG-PET/CT at baseline that strongly correlates with a poorer prognosis for MM patients. [ABSTRACT FROM AUTHOR]

The article presents information on a study which evaluates all the available scientific evidence concerning TCDD carcinogenicity. The International Agency for Research of Cancer convened a Working group to carry out the study. The study was based on evidence from epidemiologic studies and from animal experiments. It was found that NHL lymphoma is the most affected target of the carcinogenic action of TCDD.

Background: Upfront single or tandem ASCT still represents an integral part of treatment for patients with multiple myeloma. The combination of intermediate dose (ID) - cyclophosphamide plus G-CSF, has been considered the standard method as mobilization regimen. No prospective randomized clinical trials have compared efficacy and costs using ID - cyclophosphamide against a chemo-free mobilization strategy with G-CSF and plerixafor on demand., Methods: A prospective single arm of 20 patients enrolled in three Italian Centers mobilized with G-CSF plus plerixafor on demand was compared with a retrospective historical control arm of 30 patients mobilized with ID - cyclophosphamide (4 g/sqm) and G-CSF. Costs of the prospective arm was compared with the ones of the retrospective control arm with the aim to collect ≥4 × 10 6 /kg CD34 + . The exploratory cost analysis was performed using microcosting specific inputs of G-CSF plus plerixafor on demand versus ID - cyclophosphamide + G-CSF considering pre-apheresis, peri-apheresis and post-apheresis session., Results: Mobilization with ID - cyclophosphamide and G-CSF resulted in a significantly higher CD34+ peak mean on day 1 yield (119 CD34+ μL vs 67.3; p = 0.06) and in total average CD34+ yield (mean collection 10.6 × 10 6 /kg vs 5.8 × 10 6 /kg; p = 0.004) compared to patients mobilized with G-CSF and plerixafor. There was no significant differences (p = 0.36) in the two groups of patients collecting ≥ 4 million CD34+/Kg with ID - cyclophosphamide and G-CSF (93.3 %) vs G-CSF and plerixafor (90.0 %). None of the patients undergoing G-CSF and plerixafor mobilization had febrile neutropenia compared with 7 patients who received ID - cyclophosphamide and G-CSF (0% vs 23 %, p = 0.03) who had a median of 5 days hospitalization (range 4-6). All patients proceeded to ASCT with a mean of 3.6 CD34+/kg infused for G-CSF and plerixafor arm and 4.4 CD34+/kg for the ID - cyclophosphamide + GCSF group (p = 0.37) with a median time to ANC and PLT engraftment not different in the two groups. Total costs of a mobilizing strategy using a combination of G-CSF and plerixafor on demand was 12.690 euros compared to 16.088 euros with ID - cyclophosphamide and G-CSF (p = 0.07); in particular, mobilization cost components were significantly lower for G-CSF and plerixafor vs G-CSF and ID - cyclophosphamide for hospital stay (3080 euros vs 9653 euros; p < 0.001) whereas for mobilizing agent, there was a significative difference with 5470 euros for G-CSF and plerixafor use due to the cost of plerixafor compared with 1140 euros for ID - cyclophosphamide and G-CSF treatment (P = 0.001)., Conclusions: Our data demonstrate that in patients with multiple myeloma eligible for ASCT, a chemo-free mobilization with G-CSF and plerixafor on demand is associated with efficacy in PBSC collection and optimal safety profile with similar average costs when compared to a chemo-mobilization with ID - cyclophosphamide. A prospective randomized multicenter study could address which is the most cost-effective strategy for this setting of patients., Clinical Trial Registry: Eudract Number EudraCT 2013-004690-27., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

Objectives: The treatment paradigm in newly diagnosed multiple myeloma (NDMM) is evolving toward individualized, risk-directed, and longer duration of therapy (DOT). The objective of this study was to describe treatment patterns and outcomes in non-transplant NDMM in four European countries., Methods: This retrospective chart review included adults with NDMM diagnosed between January 1, 2012, and December 31, 2013 (early cohort), or April 1, 2016, and March 31, 2017 (recent cohort)., Results: Among 836 patients, molecular testing was performed in 21% and 35% patients of early vs recent cohorts; proteasome inhibitor (PI)/alkylator combinations were the principal first-line (1 L) therapy (39% vs 43%). Use of immunomodulatory drug (IMID)/alkylator combinations declined from early to recent cohort (26% vs 13%) but IMID (7% vs 16%) use increased. Few patients (5%) received 1 L maintenance therapy. Two-thirds of patients were treated with a fixed duration intent, with a median 7-month 1 L DOT and progression-free survival (PFS) of 32.8 months in the early cohort. Both 1 L DOT and PFS were longer with oral compared to injectable regimens., Conclusions: Although frontline treatment patterns changed significantly, 1 L DOT is short. The uptake of molecular testing and 1 L maintenance is low. These results highlight areas of unmet need in NDMM., (© 2020 The Authors. European Journal of Haematology published by John Wiley & Sons Ltd.)

Background: Bone complications (pathologic fracture, spinal cord compression, surgery to bone and radiation to bone) are a common problem in patients with multiple myeloma (MM). We set out to provide insights into the real-world burden of bone complications in patients with newly diagnosed MM (NDMM)., Methods: We conducted a retrospective review of medical charts of patients with NDMM whose disease had progressed following first-line treatment in the 3 months before data collection in 2016 in five European countries (France, Germany, Italy, Spain and the United Kingdom)., Results: The aggregated study population included 813 patients. Bone pain commonly led to MM diagnosis (63%) and 74% of all patients had two or more bone lesions at initiation of first-line treatment. Furthermore, 26% of patients experienced a new bone complication between MM diagnosis and disease progression following first-line treatment, despite 75% of individuals receiving bisphosphonates. Most bone complications (52%) occurred in the period before initiation of first-line treatment (mean duration: 2.3 months) and more than half of patients (56%) who experienced a new bone complication were hospitalised. Analgesics were used more frequently in patients with bone complications than in those without them (76% vs 50%, respectively). Furthermore, 51% of patients had renal impairment by the time first-line treatment was started. Overall, 25% of patients did not receive bisphosphonates for prevention of bone complications and one in four of those with renal impairment at initiation of first-line treatment did not receive bisphosphonates., Conclusions: Bone complications are common in patients with NDMM. They are frequently associated with hospitalization and analgesic use. Data from this study, conducted in the era of novel anti-myeloma therapies and before the approval of denosumab for use in patients with MM, suggest that although most patients (75%) received bisphosphonates, use of anti-resorptive therapy for prevention of bone complications may be suboptimal in patients with NDMM, irrespective of renal function.

Common childhood infectious diseases have been associated with a reduced risk of following haematopoietic malignancies, but investigations on multiple myeloma (MM) are scarce. Information about 213 MM cases and 1128 healthy controls were obtained from a multicentre population-based Italian case-control study. The association between chickenpox, measles, mumps, pertussis and rubella and the MM risk was estimated by unconditional logistic regression, adjusting for age, gender and residence area. No association was found between MM risk and any considered infectious disease. The number of infections was slightly inversely associated with the risk of MM, but statistical significance was not reached (OR 0.87, 95% CI 0.55-1.4 for 1-2 diseases vs. none and OR 0.68, 95% CI 0.41-1.1 for 3-5 diseases, respectively, P = 0.131). We did not find a clear evidence that common infections during childhood are associated with the subsequent risk of developing MM.

ᅟ: FDG PET/CT ( 18 F-fluoro-deoxy-glucose positron emission tomography/computed tomography) is a useful tool to image multiple myeloma (MM). However, simple and reproducible reporting criteria are still lacking and there is the need for harmonization. Recently, a group of Italian nuclear medicine experts defined new visual descriptive criteria (Italian Myeloma criteria for Pet Use: IMPeTUs) to standardize FDG PET/CT evaluation in MM patients. The aim of this study was to assess IMPeTUs reproducibility on a large prospective cohort of MM patients., Materials and Methods: Patients affected by symptomatic MM who had performed an FDG PET/CT at baseline (PET0), after induction (PET-AI), and the end of treatment (PET-EoT) were prospectively enrolled in a multicenter trial (EMN02)(NCT01910987; MMY3033). After anonymization, PET images were uploaded in the web platform WIDEN® and hence distributed to five expert nuclear medicine reviewers for a blinded independent central review according to the IMPeTUs criteria. Consensus among reviewers was measured by the percentage of agreement and the Krippendorff's alpha. Furthermore, on a patient-based analysis, the concordance among all the reviewers in terms of positivity or negativity of the FDG PET/CT scan was tested for different thresholds of positivity (Deauville score (DS 2, 3, 4, 5) for the main parameters (bone marrow, focal score, extra-medullary disease)., Results: Eighty-six patients (211 FDG PET/CT scans) were included in this analysis. Median patient age was 58 years (range, 35-66 years), 45% were male, 15% of them were in stage ISS (International Staging System) III, and 42% had high-risk cytogenetics. The percentage agreement was superior to 75% for all the time points, reaching 100% of agreement in assessing the presence skull lesions after therapy. Comparable results were obtained when the agreement analysis was performed using the Krippendorff's alpha coefficient, either in every single time point of scanning (PET0, PET-AI or PET-EoT) or overall for all the scans together. DS proved highly reproducible with the highest reproducibility for score 4., Conclusions: IMPeTUs criteria proved highly reproducible and could therefore be considered as a base for harmonizing PET interpretation in multiple myeloma. A prospective clinical validation of IMPeTUs criteria is underway.

90 cases of paraproteinemia treated for 12 years, have been studied. The results, documented by a clinical and bio-humoral point of view, have been compared with those of largest and latest casistics. The Authors tried to see if there were some connections between serology, radiology, histology and clinical pictures of different cases of paraproteinemia both as far as the classes and the types. The clinical, registrar and hospital information about the homogeneous population of Saronno have been asked in order to consider the course of the illness continuously. Also the follow-up has been compared with the data of the specific literature. The obtained data are almost similar to those of the most accurate works which have been described.