Multiple Myeloma Treatment in Real-world Clinical Practice : Results of a Prospective, Multinational, Noninterventional Study

Funding Information: The authors would like to thank all patients and their families and all the EMMOS investigators for their valuable contributions to the study. The authors would like to acknowledge Robert Olie for his significant contribution to the EMMOS study. Writing support during the development of our report was provided by Laura Mulcahy and Catherine Crookes of FireKite, an Ashfield company, a part of UDG Healthcare plc, which was funded by Millennium Pharmaceuticals, Inc, and Janssen Global Services, LLC. The EMMOS study was supported by research funding from Janssen Pharmaceutical NV and Millennium Pharmaceuticals, Inc. Funding Information: The authors would like to thank all patients and their families and all the EMMOS investigators for their valuable contributions to the study. The authors would like to acknowledge Robert Olie for his significant contribution to the EMMOS study. Writing support during the development of our report was provided by Laura Mulcahy and Catherine Crookes of FireKite, an Ashfield company, a part of UDG Healthcare plc, which was funded by Millennium Pharmaceuticals, Inc, and Janssen Global Services, LLC. The EMMOS study was supported by research funding from Janssen Pharmaceutical NV and Millennium Pharmaceuticals, Inc. Funding Information: M.M. has received personal fees from Janssen, Celgene, Amgen, Bristol-Myers Squibb, Sanofi, Novartis, and Takeda and grants from Janssen and Sanofi during the conduct of the study. E.T. has received grants from Janssen and personal fees from Janssen and Takeda during the conduct of the study, and grants from Amgen, Celgene/Genesis, personal fees from Amgen, Celgene/Genesis, Bristol-Myers Squibb, Novartis, and Glaxo-Smith Kline outside the submitted work. M.V.M. has received personal fees from Janssen, Celgene, Amgen, and Takeda outside the submitted work. M.C. reports honoraria from Janssen, outside the submitted work. M. B. reports grants from Janssen Cilag during the conduct of the study. M.D. has received honoraria for participation on advisory boards for Janssen, Celgene, Takeda, Amgen, and Novartis. H.S. has received honoraria from Janssen-Cilag, Celgene, Amgen, Bristol-Myers Squibb, Novartis, and Takeda outside the submitted work. V.P. reports personal fees from Janssen during the conduct of the study and grants, personal fees, and nonfinancial support from Amgen, grants and personal fees from Sanofi, and personal fees from Takeda outside the submitted work. W.W. has received personal fees and grants from Amgen, Celgene, Novartis, Roche, Takeda, Gilead, and Janssen and nonfinancial support from Roche outside the submitted work. J.S. reports grants and nonfinancial support from Janssen Pharmaceutical during the conduct of the study. V.L. reports funding from Janssen Global Services LLC during the conduct of the study and study support from Janssen-Cilag and Pharmion outside the submitted work. A.P. reports employment and shareholding of Janssen (Johnson & Johnson) during the conduct of the study. C.C. reports employment at Janssen-Cilag during the conduct of the study. C.F. reports employment at Janssen Research and Development during the conduct of the study. F.T.B. reports employment at Janssen-Cilag during the conduct of the study. The remaining authors have stated that they have no conflicts of interest. Publisher Copyright: © 2018 The AuthorsMultiple myeloma (MM) remains an incurable disease, with little information available on its management in real-world clinical practice. The results of the present prospective, noninterventional observational study revealed great diversity in the treatment regimens used to treat MM. Our results also provide data to inform health economic, pharmacoepidemiologic, and outcomes research, providing a framework for the design of protocols to improve the outcomes of patients with MM. Background: The present prospective, multinational, noninterventional study aimed to document and describe real-world treatment regimens and disease progression in multiple myeloma (MM) patients. Patients and Methods: Adult patients initiating any new MM therapy from October 2010 to October 2012 were eligible. A multistage patient/site recruitment model was applied to minimize the selection bias; enrollment was stratified by country, region, and practice type. The patient medical and disease features, treatment history, and remission status were recorded at baseline, and prospective data on treatment, efficacy, and safety were collected electronically every 3 months. Results: A total of 2358 patients were enrolled. Of these patients, 775 and 1583 did and did not undergo stem cell transplantation (SCT) at any time during treatment, respectively. Of the patients in the SCT and non-SCT groups, 49%, 21%, 14%, and 15% and 57%, 20%, 12% and 10% were enrolled at treatment line 1, 2, 3, and ≥ 4, respectively. In the SCT and non-SCT groups, 45% and 54% of the patients had received bortezomib-based therapy without thalidomide/lenalidomide, 12% and 18% had received thalidomide/lenalidomide-based therapy without bortezomib, and 30% and 4% had received bortezomib plus thalidomide/lenalidomide-based therapy as frontline treatment, respectively. The corresponding proportions of SCT and non-SCT patients in lines 2, 3, and ≥ 4 were 45% and 37%, 30% and 37%, and 12% and 3%, 33% and 27%, 35% and 32%, and 8% and 2%, and 27% and 27%, 27% and 23%, and 6% and 4%, respectively. In the SCT and non-SCT patients, the overall response rate was 86% to 97% and 64% to 85% in line 1, 74% to 78% and 59% to 68% in line 2, 55% to 83% and 48% to 60% in line 3, and 49% to 65% and 36% and 45% in line 4, respectively, for regimens that included bortezomib and/or thalidomide/lenalidomide. Conclusion: The results of our prospective study have revealed great diversity in the treatment regimens used to manage MM in real-life practice. This diversity was linked to factors such as novel agent accessibility and evolving treatment recommendations. Our results provide insight into associated clinical benefits.publishersversionPeer reviewe

Value of autopsy in Internal Medicine: discrepancies between clinical and postmortem diagnosis

Introduction The number of autoptic controls is progressively dropping worldwide during the last decades. Several social, cultural and normative causes may underlie this phenomenon. However, a hidden cause may be represented by the scepticism of physicians about the gain in information given by this practice. There is in fact a general thinking that available diagnostic techniques may be adequate for a correct diagnosis, even in the case of a mortal outcome. Nevertheless, several studies have shown quite relevant discrepancies between premortem and postmortem diagnosis. In this study, the authors evaluate the accuracy of clinical diagnosis in diseases leading the patient to death.Materials and methods Retrospective analysis including all patients died in the Department of Internal Medicine of a General Hospital in Rome during a three year time period (1st January 2007–31 December 2009). Age, sex, period of hospitalization, clinical diagnosis, autoptic diagnosis, cause of death, and level of discrepancy between clinical diagnosis and autoptic control have been collected. Main diagnoses have been classified as follows: (1) discrepancy with a possible influence on survival; (2) discrepancy with no or questionable influence on survival.Results Ninety-two cases (42 males, 50 females; mean age 79.3 years) have been included. Thirty-four main diagnoses (36.9%) have been classified as discrepant (15.2% classified as type 1 discrepancy and 21.7 as type 2).DiscussionA substantial discrepancy between clinical diagnosis and autoptic control is confirmed by the current study, which supports the role of autopsy as a tool for the improvement of medical practice.</p

Emphysematous pyelonephritis: a case report

Emphysematous pyelonephritis is a severe, life-threatening, necrotizing kidney disease. It occurs almost exclusively in patients with diabetes mellitus. The clinical manifestations are those of pyelonephritis such as dysuria, fever, nausea, vomiting and abdominal pain. The diagnosis is radiological. The treatment strategies are controversial. They include medical management only, percutaneous catheter drainage plus medical management, emergency nephrectomy plus medical treatment or percutaneous drainage plus medical management and emergency nephrectomy. We present the case of a 68-year-old woman affected by emphysematous pyelonephritis successfully managed with conservative medical treatment

Quality of diabetes mellitus therapy in patients with chronic kidney disease in the real world

Chronic kidney disease (CKD) is very often among diabetic patients. Some oral antidiabetic agents are not recommended in the presence of CKD. Aim of the study was to evaluate the quality of diabetes mellitus (DM) treatment in nephrophatic patients in the real world. A total of 265 subjects with type 2 DM, consecutively admitted to the internal medicine departments of two hospitals in Rome, were recruited. Patients hospitalized for hypoglycemia, decompensated DM, acute kidney failure or worsening nephropathy were excluded. For each patient, the following data were collected: age, gender, estimated glomerular filtration rate (eGFR) using the MDRD (modification of diet in renal disease) study equation, type of antidiabetic drug treatment. A total of 265 subjects were studied, 127 male (47.9%) and 138 female (52.1%). The mean age was 77.5 years. The mean of glycemia glycated hemoglobin (HbA1c) value was 57.5 mmol/mol (7.4%). 137 patients (51.7%) were treated with oral antidiabetic agents, 29 (10%) with both oral antidiabetic agents and insulin, 90 (34%) with insulin alone, 8 (3%) with dipeptidyl peptidase-4 inhibitors, 1 (0.4%) with incretin agents plus oral antidiabetic drugs. According to the Kidney Disease Outcomes Quality Initiative (KDOQI) classification of CKD, the sample was divided into 5 groups using eGFR criteria. For each group, mean HbA1c values, type of antidiabetic treatment, appropriateness of therapy according to guidelines and how it may affect the HbA1c levels were considered. Our data show that 30.5% of patients with CKD stage 3-5 is treated with drugs not recommended by current guidelines

CD38 Ligation in Peripheral Blood Mononuclear Cells of Myeloma Patients Induces Release of Protumorigenic IL-6 and Impaired Secretion of IFNγ Cytokines and Proliferation

CD38, a surface receptor that controls signals in immunocompetent cells, is densely expressed by cells of multiple myeloma (MM). The immune system of MM patients appears as functionally impaired, with qualitative and quantitative defects in T cell immune responses. This work answers the issue whether CD38 plays a role in the impairment of T lymphocyte response. To this aim, we analyzed the signals implemented by monoclonal antibodies (mAb) ligation in peripheral blood mononuclear cells (PBMC) obtained from MM patients and compared to benign monoclonal gammopathy of undetermined significance (MGUS). PBMC from MM both failed to proliferate and secrete IFNγ induced by CD38 ligation while it retained the ability to respond to TCR/CD3. The impaired CD38-dependent proliferative response likely reflects an arrest in the progression of cell cycle, as indicated by the reduced expression of PCNA. CD38 signaling showed an enhanced ability to induce IL-6 secretion. PBMC from MM patients displays a deregulated response possibly due to defects of CD38 activation pathways and CD38 may be functionally involved in the progression of this pathology via the secretion of high levels of IL-6 that protects neoplastic cells from apoptosis

The change of hospital internal medicine: a study on patients admitted in internal medicine wards of 8 hospitals of the Lazio area, Italy

The hospital internal medicine (IM) needs to adapt to the socio-demographic changes occurred during the last thirty years: patients currently show an increased overall complexity owing to the increase in the average age of the patients admitted, to more several and severe comorbidities, and a higher concentration in our wards of most severe cases. Our departments have to change in order to pursue a more efficient organization and to offer care to users modulated according to their needs and conditions. The Intensity of Care in Internal Medicine Group of the Federation of Associations of Hospital Doctors on Internal Medicine - Lazio carried out a population-based study in eight Internal Medicine wards of the region with the aim of characterizing the patients there admitted, using the modified early warning score (mEWS), monitoring and evaluating the outcomes of hospitalization. This has allowed us to determine the cut-off of the score indicating a greater statistical probability of a fatal outcome corresponding to 3, contrary to what originally reported by Subbe et al. in 2001. According to our results into the Departments of IM should be provided an area of high care, where monitor and stabilize the patients admitted with a mEWS score ≥3, before transferring them to the wards of lower intensity of care. This organizational model of the high care of medical patients has the benefit of offer the technical and professional assistance appropriate to the level of clinical risk, with more intensive care to more critical stages of illness

Quality of life in elderly patients with essential thrombocythaemia. An Italian multicentre study

Essential thrombocythaemia (ET) is a myeloproliferative neoplasm characterized by elevated platelet counts and increased incidence of thrombosis and haemorrhage. Median age at diagnosis is 65-70 years. Life expectancy is similar to that of the healthy population. Symptoms and complications may affect quality of life (QoL); in particular, in elderly patients ET may represent an additional burden. We performed a survey in 494 elderly ET patients to evaluate patient-reported outcomes (PROs). Comorbidities were present in 305 (62%) patients. Factorial analysis based on survey items representing psychological aspects of daily life identified an "attitude domain" with four clusters of patients: (A) very pessimistic (n = 99), (B) pessimistic (n = 101), (C) optimistic (n = 90), and (D) very optimistic (n = 107). Patients in cluster A had more comorbidities (p = 0.003) while patients in cluster D required fewer medical visits and were less disturbed by medications (p < 0.0001). Independent factors predicting Short-Form Health Survey, version 2 physical QoL were grade of optimism (p < 0.0001), gender (p = 0.007), and Charlson comorbidity index (p < 0.0001)). Grade of optimism and disturbances related to medication predicted mental QOL (p < 0.0001). In conclusion, physicians should take into consideration PROs, as "attitude" is associated with physical and mental QoL. Treatment should be tailored to patients' needs according to comorbidities, lifestyle, and psychological conditions

HPV vaccination after primary treatment of HPV-related disease across different organ sites: a multidisciplinary comprehensive review and meta-analysis

Objective: To assess evidence on the efficacy of adjuvant human papillomavirus (HPV) vaccination in patients treated for HPV-related disease across different susceptible organ sites. Methods: A systematic review was conducted to identify studies addressing the efficacy of adjuvant HPV vaccination on reducing the risk of recurrence of HPV-related preinvasive diseases. Results were reported as mean differences or pooled odds ratios (OR) with 95% confidence intervals (95% CI). Results: Sixteen studies were identified for the final analysis. Overall, 21,472 patients with cervical dysplasia were included: 4132 (19.2%) received the peri-operative HPV vaccine, while 17,340 (80.8%) underwent surgical treatment alone. The recurrences of CIN 1+ (OR 0.45, 95% CI 0.27 to 0.73; p = 0.001), CIN 2+ (OR 0.33, 95% CI 0.20 to 0.52; p &lt; 0.0001), and CIN 3 (OR 0.28, 95% CI 0.13 to 0.59; p = 0.0009) were lower in the vaccinated than in unvaccinated group. Similarly, adjuvant vaccination reduced the risk of developing anal intraepithelial neoplasia (p = 0.005) and recurrent respiratory papillomatosis (p = 0.004). No differences in anogenital warts and vulvar intraepithelial neoplasia recurrence rate were observed comparing vaccinated and unvaccinated individuals. Conclusions: Adjuvant HPV vaccination is associated with a reduced risk of CIN recurrence, although there are limited data regarding its role in other HPV-related diseases. Further research is warranted to shed more light on the role of HPV vaccination as adjuvant therapy after primary treatment