Non-interventional Retrospective Study Research Articles

A non-interventional retrospective study to describe early clinical experience with cabozantinib in patients with advanced renal cell carcinoma (aRCC) in the United Kingdom.

e17089 Background: Cabozantinib is approved in the UK in treatment-naïve adults with intermediate or poor risk aRCC or following prior VEGF-targeted therapy. Here we describe treatment pathways and clinical outcomes of patients with aRCC who received cabozantinib early and later in the UK managed access program (MAP) as disease severity may differ in these patient populations. Methods: A non-interventional retrospective chart review study was carried out in six specialist centres in the UK to describe early clinical experience with cabozantinib in patients with aRCC (CERES, NCT03696407). Progression-free survival (PFS) and overall survival (OS) were calculated from cabozantinib initiation using the Kaplan-Meier method. Patients were grouped into those who initiated cabozantinib early (Aug 2016-Feb 2017) or late (Mar-Aug 2017) in the MAP. Results: Overall 100 patients were eligible; median (95%CI) PFS was 6.01 (5.16; 7.85) months and median OS was 10.84 (7.92; 16.85) months. Patients in the early MAP group received a mean (SD) of 2.2 (1.4) lines of prior therapy, most commonly sunitinib (n = 32, 56.1%) and pazopanib (n = 30, 52.6%). Patients in the late MAP group received a mean of 1.9 (SD 1.2) lines of prior therapy, most commonly pazopanib (n = 23, 53.5%) and sunitinib (n = 19, 44.2%). At least one post-cabozantinib therapy was prescribed in 44.6% (25/57) and 27.9% (12/43) of patients in the early and late groups, respectively, most commonly nivolumab (both groups). See table for characteristics and outcomes by MAP group. Conclusions: Cabozantinib was effective in this small, real-world study of patients receiving treatment as part of a MAP. The results are supportive of the data seen in the registrational study, METEOR. Patients enrolled early in the MAP were possibly more heavily pre-treated but overall outcomes were similar to those who enrolled later. [Table: see text]

Fluconazole vs. voriconazole prophylaxis for prevention of invasive fungal infections post haploidentical stem cell transplant.

e19504 Background: IFIs are one of the most detrimental complications of profound and prolonged neutropenia post-allogeneic SCT. Prophylaxis with broad spectrum azole antifungals has become standard of care given favorable outcomes associated with their use in this setting. Nonetheless, the choice of antifungal agent varies between institutions due to absence of consensus guidelines in patients undergoing haploidentical SCT. Methods: Non-interventional retrospective study seeking to compare efficacy of fluconazole vs. voriconazole for prevention of IFI post haploidentical SCT for hematologic malignancies. SCT databases at two academic insitutions (one uses fluconazole and other uses voriconazole) were queried to identify patients who underwent allogeneic SCT from April 2012 until March 2018, and received prophlaxis with either voriconazole (group I) or fluconazole (group II). Patients with intent to start prophylaxis with fluconazole or voriconazole were included, even if antifungal agent was changed later. Primary endpoint was cumulative incidence of breakthrough IFIs (based on MSG criteria) on day +100 and +180. Fisher exact test was used to compare rates of breakthrough IFIs between two cohorts. Secondary endpoint was overal survival (OS). Kaplan Meiers analysis was performed to compare OS on day +180 and 1-year post SCT. Results: The cohort included 141 patients (group I: 75 and group II: 66). Percentage of patients who underwent transplant for leukemia was higher in group I compared to group II (77.3% vs. 56.1%, p < 0.001). A haploidentical SCT was performed in 62.7% of patients in group I compared to 100% in group II (p < 0.001). All patients received non-myeloablative conditioning. There was no statistically significant difference in rates of IFIs between two groups on day +100 (0% in I vs. 4.5% in II, p = 0.9) and +180 (1.4% vs. 4.6%, p = 0.2). A significant difference in OS was noted on day +180 and at 1-year in univariate analysis (Table). Conclusions: Our findings suggest that prophylactic use of either voriconazole or fluconazole after haploidentical SCT is associated with low rates of IFIs. However, survival data favored voriconazole over fluconazole. [Table: see text]

Nosocomial infection with SARS-Cov-2within Departments of Digestive Surgery.

SummaryIntroductionThe COVID-19 pandemic imposed a drastic reduction in surgical activity in order to respond to the influx of hospital patients and to protect uninfected patients by avoiding hospitalization. However, little is known about the risk of infection during hospitalization or its consequences. The aim of this work was to report a series of patients hospitalized on digestive surgery services who developed a nosocomial infection with SARS-Cov-2 virus.MethodsThis is a non-interventional retrospective study carried out within three departments of digestive surgery. The clinical, biological and radiological data of the patients who developed a nosocomial infection with SARS-Cov-2 were collected from the computerized medical record.ResultsFrom March 1, 2020 to April 5, 2020, among 305 patients admitted to digestive surgery departments, 15 (4.9%) developed evident nosocomial infection with SARS-Cov-2. There were nine men and six women, with a median age of 62 years (35–68 years). All patients had co-morbidities. The reasons for hospitalization were: surgical treatment of cancer (n = 5), complex emergencies (n = 5), treatment of complications linked to cancer or its treatment (n = 3), gastroplasty (n = 1), and stoma closure (n = 1). The median time from admission to diagnosis of SARS-Cov-2 infection was 34 days (5–61 days). In 12 patients (80%), the diagnosis was made after a hospital stay of more than 14 days (15–63 days). At the end of the follow-up, two patients had died, seven were still hospitalized with two of them on respiratory assistance, and six patients were discharged post-hospitalization.ConclusionsThe risk of SARS-Cov-2 infection during hospitalization or following digestive surgery is a real and potentially serious risk. Measures are necessary to minimize this risk in order to return to safe surgical activity.

Infection nosocomiale à SARS-Cov-2 dans les services de chirurgie digestive

RésuméIntroductionLa pandémie de COVID-19 a imposé une diminution radicale de l’activité chirurgicale afin de répondre à l’afflux de patients hospitalisés et protéger les patients non infectés en leur évitant une hospitalisation. Toutefois, le risque d’infection lors de l’hospitalisation et ses conséquences sont encore très peu connus. Le but de ce travail était de rapporter une série de patients hospitalisés en chirurgie digestive chez qui une infection nosocomiale à SARS-Cov-2 a été diagnostiquée.MéthodesÉtude rétrospective non-interventionnelle réalisée au sein de 3 services de chirurgie digestive. Les données cliniques, biologiques et radiologiques des patients ayant développé une infection nosocomiale au SARS-Cov-2 ont été collectées à partir des dossiers informatisés.RésultatsDu 1er mars 2020 au 5 avril 2020, parmi 305 patients admis en chirurgie digestive, 15 (4,9 %) ont présenté une infection nosocomiale à SARS-Cov-2. Il s’agissait de 9 hommes et 6 femmes, d’un âge médian de 62 ans (35-68 ans). Tous les patients avaient une comorbidité. Les motifs d’hospitalisation étaient : traitement chirurgical d’un cancer (n = 5), urgences complexes (n = 5), traitement de complications liées au cancer ou à son traitement (n = 3), reconstruction par gastroplastie (n = 1), fermeture de stomie (n = 1). Le délai médian entre l’admission et le diagnostic d’infection à SARS-Cov-2 était de 34 jours (5-61 jours). Chez 12 (80 %) patients, le diagnostic a été posé après une durée d’hospitalisation de plus de 14 jours (15-63 jours). À l’issue du suivi, 2 patients sont décédés, 7 étaient encore hospitalisés dont 2 sous assistance respiratoire et 6 patients étaient sortis d’hospitalisation.ConclusionsLe risque d’infection au SARS-Cov-2 au cours d’une hospitalisation ou dans les suites d’une intervention de chirurgie digestive est un risque réel et potentiellement grave. Des mesures sont nécessaires afin de minimiser ce risque dans la perspective d’une reprise de l’activité chirurgicale en toute sécurité.

Dengue Severity Risk Factors in New Caledonia - Design of Predictive Tool Usable By Doctors during the First Consultation

Objectives: In New Caledonia (NC), Dengue circulation was detected every year since last decade. The 2017 epidemic have affected 4,379 people with 11.5% of hospital admission and 15 deaths. The aim of this work is to study the risk factors of severe dengue during the 2017 outbreak and to develop a predictive tool, based on a model, usable by doctors during the first consultation to early assess the risk for a dengue patient to progress to a severe form. Study design: This is a non-interventional retrospective study in which a cohort of hospitalized and non-hospitalized cases, positive for dengue virus infection by qRTPCR was documented. Methods: Patients were classified in severe or non-severe dengue. We explored the association of dengue severity to patients’ characteristics, symptoms at the first consultation, dengue serotype and previous Zika and dengue infection. A predictive model of the severity usable at first consultation was built using a multivariate analysis and a cross-validation procedure. Results: A total of 771 dengue cases were studied, with 134 patients who developed severe dengue fever. The dengue serotype does not appear to influence the severity of the infection, whereas, an anterior dengue seems to be significantly related to a severe form. We created two predictive models based on patient characteristics and clinical signs, one for and one for men because of the sex and age class interaction. For both models, the variables were: age, selfdeclared ethnicity, alert signs (mucosal bleedizg, clinical liquid accumulation, abdominal pain, lethargy or anxiety) and for women model added variables were arterial hypertension, platelet aggregation inhibitor and anticoagulants treatments. The average and median AUC values for both models are > 0.80 which shows a fairly good model quality; moreover high negative predictive values (> 95%) indicate that models are quite protective. Conclusion: This study described severity and risk factors for both hospitalized and non-hospitalized patients. The developed models can be used at the first consultation and doctors will be able to early assess the risk for dengue patient to progress to a severe form and increased surveillance with possible hospitalization.

Real Life Experience in Clinical Practice with Recombinant Coagulation FVIII-Fc Fusion Protein

Introduction: Efmoroctocog alfa (Elocta®) is a recombinant coagulation FVIII-Fc (rFVIIIFc), a fully recombinant fusion protein produced in human embryonic kidney cells, with an extended half-life used for the treatment and prevention of bleeding in patients with severe hemophilia A. Using rFVIIIFc for the treatment of severe hemophilia A patients received the approval of reimbursement in Spain at the end of 2016. Therefore, there are no many comparative data published about real life use of rFVIIIFc. Objective: This work aims to describe characteristics of the treatment of severe hemophilia A patients with rFVIIIFc and to compare its results with those previously obtained employing other FVIII products. Methods: This was an open-label non-interventional retrospective study reviewing patient characteristics and treatment outcomes before and after the use of rFVIIIFc. The La Paz University Hospital Ethics Committee approved the experimental protocol. Patients with severe hemophilia A without inhibitors being treated with rFVIIIFc since at least six months before study approval by Ethics Committee were included. The following data were collected for patients included in the study: dose (IU/kg) and prophylaxis treatment regimen, number of spontaneous and traumatic bleedings, annual bleeding rate (ABR) and FVIII trough level. The statistical analysis on the variables listed above comparing before and after rFVIIIFc usage was performed by the Biostatistics Unit of La Paz University Hospital with the statistical package SPSS v.18.0 (SPSS Inc., Chicago, IL, USA). Results: Twenty two severe hemophilia A patients (median age: 20 years old, ranging from 6 to 63 years) on prophylaxis with rFVIIIFc were considered to be included in this study, but two were excluded due to lack of data. Median follow-up period was 14 months (ranging from 6 to 28 months). Nineteen severe hemophilia A patients have been previously treated with rFVIII (two of them with other extended half-life product) and one with plasma-derived FVIII. Eight of the ten severe hemophilia A patients who presented an ABR greater than 0 with previous treatments reduced their ABR when treated with rFVIIIFc (Table 1). Among those patients with an ABR=0 with previously used FVIII products, only one increased to an ABR=1 when treated with Elocta® due to a traumatic bleeding. Table 1 shows ABR across all patients before and after rFVIIIFc. There was no difference in dose per injection between other FVIII products and rFVIIIFc (median dose for patients treated with other FVIII products: 46.0 IU/kg, ranging from 26 to 65 IU/kg; median dose for patients treated with rFVIIIFc: 46.5 IU/kg, ranging from 26 to 65 IU/kg). Nevertheless, a reduction was observed in administration frequency. Among the twelve patients who received treatment with other FVIII products every 48 hours, eleven came to receive rFVIIIFc 3 times a week and the one previously receiving a plasma-derived FVIII, to twice a week. Five of the patients receiving treatment 3 times a week reduced its frequency to twice per week. Three patients maintained the same schedule of administration. To note, one of the two patients receiving another prolonged half-life product maintained the schedule of treatment and the other reduced its frequency from every 48 hours to 3 times a week. FVIII trough level in plasma (% of FVIII), expressed as median (25th-75th percentile), was 1.1 (0.1-4.0) for rFVIIIFc treatment and 0.2 (0.0-1.9) for other FVIII products (p=0.06). Conclusions: 85% of the severe hemophilia A patients from our cohort reduced the weekly dose administration after beginning treatment with rFVIIIFc. Most of the patients increased plasma trough level of FVIII with rFVIIIFc. 45% of patients reduced and 40% kept their ABR=0 when they changed rFVIIIFc. These data suggest that treatment with rFVIIIFc gives a higher protection to severe hemophilia A patients. However, further research with larger sample size is required to investigate this. This work was supported by SOBI. NB holds a tenure track grant from FIS-FONDOS FEDER (CP14/00024). Disclosures Álvarez Roman: Takeda: Research Funding; Amgen: Consultancy, Speakers Bureau; NovoNordisk: Consultancy, Speakers Bureau; Novartis: Consultancy, Speakers Bureau; Bayer: Consultancy, Speakers Bureau; Pfizer: Consultancy, Speakers Bureau; Roche: Consultancy, Speakers Bureau; CSL Behring: Consultancy, Speakers Bureau; Sobi: Consultancy, Speakers Bureau. Fernandez-Bello:Novartis, Pfizer, ROCHE, Stago: Speakers Bureau. Martín:SOBI: Research Funding; Novartis, Pfizer, ROCHE, Novo Nordisk: Speakers Bureau. Rivas Pollmar:Novartis, Pfizer, ROCHE, Novo Nordisk: Speakers Bureau; SOBI: Research Funding. García Barcenilla:Bayer, Pfizer, Takeda, Novartis: Speakers Bureau; SOBI: Research Funding. Canales:SOBI: Research Funding; iQone: Honoraria; Karyopharm: Honoraria; Novartis: Honoraria; Takeda: Speakers Bureau; Gilead: Honoraria; Celgene: Honoraria; Janssen: Honoraria, Speakers Bureau; F. Hoffmann-La Roche Ltd: Honoraria, Speakers Bureau; Sandoz: Honoraria. Butta:Roche, Pfizer: Speakers Bureau; Novartis: Consultancy. Jimenez-Yuste:Bayer, CSL Behring, Grifols, Novo Nordisk, Octapharma, Pfizer, Roche, Sobi, Shire: Consultancy, Honoraria, Other: reimbursement for attending symposia/congresses , Research Funding, Speakers Bureau.

Retrospective Non-Interventional Assessment of the Use of Idelalisib in Relapsed/Refractory Chronic Lymphocytic Leukemia Patients in Spain

Background Idelalisib is a PI3-kinase inhibitor specific for the delta isoform, approved (in combination with rituximab or ofatumumab) for the treatment of adult patients with Relapsed/Refractory Chronic Lymphocytic Leukemia (R/R CLL). Although the efficacy of idelalisib was reported in clinical trials, it is unclear how this translates into Real World. Methods A non-interventional retrospective study was conducted in Spain to describe the clinical characteristics and outcomes of patients diagnosed with R/R CLL that started treatment with idelalisib between 1 February 2015 and 31 December 2017. The Time from start of idelalisib treatment to either the start of a new anti CLL therapy or death (Time to Next Treatment or Death - TNTD) was defined as primary endpoint. Secondary endpoints included overall survival (OS), time to discontinuation (TTD) and safety, especially Adverse Events of Special Interest (AESI): ≥ grade 3 transaminase elevations, diarrhea /colitis, pneumonitis, neutropenia,Cytomegalovirus, bacterial, fungal and respiratory virus infections (RVI),Pneumocystis jirovecii pneumonia (PjP). Results Investigators from 21 centers included 77 patients in the study. The median age was 72.1 years (48-86) and 67.5% (n=52) were male. The main baseline characteristics were: Binet stage B-C in 32.5% (n=25), 17p deletion or TP53 mutation in 35.1% (n=27) and the median number previous lines of therapy was 4 (1-16). With a median follow up time of 14.4 months (1.2-44.4), 27 patients (35.1%) had started a new treatment and 19 (24.7%) had died. The median TNTD was 17.1 months (95% CI 14.0-22.3) in the overall population and 13.8 months (95% CI 7.9-15.2) in patients that discontinued idelalisib. The median OS has not been reached, with a cumulative probability of surviving at 1 and 2 years of 0.84 (95% CI 0.73-0.91) and 0.67 (95% CI 0.52-0.78). During follow-up 54 patients (70.1%) discontinued idelalisib: 39 (72.3%) due to toxicity and 10 (18.5%) due to disease progression. The median TTD was 13.0 months (95% CI 7.7-15.8); 5.3 months (95%CI 3.8-8.0) in patients who discontinued treatment due to serious adverse events (SAE) or AESI and 10.5 months (95% CI 0.5-16.0) in those who did so due to progressive disease. A total of 355 AEs were reported, of which 29.0% (n=103) were SAE. 181 AESIs were recorded: the most frequent were neutropenia (n=67; 22 grade >3), diarrhea/colitis (n=37; 14 grade >3) and bacterial infections (n=24; 14 grade >3). Other AESI were CMV infections (n=11), grade ≥ 3 pneumonitis (n=7), RVI (n=6), fungal infections (n=5), grade ≥ 3 transaminase elevations (n=3) and PjP (n=1). The median time from Idelalisib start to first AESI was 9.5 months (95%CI 5.5-15.3). During follow-up, 19 deaths were registered, 10 of which were caused by idelalisib-related SAEs (4 respiratory infections, 2 pneumonitis, 1 diarrhea/colitis). The time from SAE related to idelalisib that led to death, to death was 0.8 months (95% CI 0.7-1.7). Conclusions This real world study shows results of effectiveness of idelalisib consistent with the efficacy findings of the 312-0116 clinical trial. Toxicity was the most common reason for idelalisib discontinuation. Findings of adverse events were consistent with the known safety profile of idelalisib and no new drug-related adverse events were identified. This is a Gilead Sciences sponsored study. Disclosures Perez Encinas: GILEAD SCIENCES: Research Funding; CELGENE: Consultancy; JANSSEN: Consultancy. Lopez Jimenez:GILEAD SCIENCES: Honoraria, Other: Education funding. Ortiz:GILEAD SCIENCES: Research Funding. Cordoba:Pfizer: Consultancy; Celgene: Consultancy, Honoraria, Speakers Bureau; FUNDACION JIMENEZ DIAZ UNIVERSITY HOSPITAL: Employment; Roche: Honoraria, Speakers Bureau; Kyowa-Kirin: Consultancy, Honoraria, Speakers Bureau; Gilead: Consultancy, Research Funding, Speakers Bureau; Servier: Consultancy, Honoraria, Speakers Bureau; Janssen: Consultancy, Honoraria, Speakers Bureau. Ramirez Payer:GILEAD SCIENCES: Research Funding. González-Barca:Roche: Consultancy, Honoraria; Janssen: Consultancy, Honoraria; Celtrion: Consultancy; AbbVie: Consultancy, Honoraria; Kiowa: Consultancy; Takeda: Honoraria; Celgene: Consultancy. Martín Sánchez:GILEAD SCIENCES: Research Funding. Sanchez:Gilead Sciences: Research Funding. Baltasar Tello:JANSSEN: Consultancy, Honoraria; ABBVIE: Honoraria; ROCHE: Honoraria; GILEAD: Honoraria. Amutio:NOVARTIS: Consultancy; JANSSEN: Consultancy, Honoraria; CELGENE: Consultancy, Honoraria; ROCHE: Honoraria; GILEAD SCIENCES: Consultancy, Honoraria; TAKEDA: Consultancy; GSK: Honoraria; BMS: Honoraria; JAZZ PHARMACEUTICALS: Honoraria; MUNDIPHARMA: Consultancy. Vidal Maceñido:GILEAD SCIENCES: Research Funding. Fernandez:GILEAD SCIENCES: Research Funding. Loscertales:Gilead: Honoraria; AbbVie: Honoraria; AstraZeneca: Honoraria; Janssen: Honoraria; Roche: Honoraria. Rodríguez:GILEAD SCIENCES: Research Funding. Alaez:ROCHE: Consultancy. Ramroth:Gilead Sciences: Employment. Palla:Gilead Sciences: Employment.

Monoclonal immunoglobulin–mediated kidney disease: What is beyond amyloidosis in real practice?

Background:Monoclonal immunoglobulin–mediated kidney disease with various patterns of damage may occur in patients with B-cell malignancies and non-malignant monoclonal gammopathies, and the latter are actually merged under the umbrella of monoclonal gammopathy of renal significance. Amyloidosis is the most well-known monoclonal immunoglobulin–related kidney damage. We focused on the rarer conditions and aimed to evaluate the non-amyloid spectrum of monoclonal immunoglobulin–mediated patterns of renal damage in real clinical practice.Methods:A single-center non-interventional retrospective study included 45 patients with pathology-proven non-amyloid monoclonal immunoglobulin–mediated kidney disease, followed during 2002–2018. Disease duration, proteinuria, serum creatinine, need for dialysis at the time of kidney biopsy, clinical diagnosis, and kidney pathology findings were analyzed.Results:No significant differences in the median age, disease duration at the time of biopsy, or main clinical presentation of kidney disease were found between patients with monoclonal gammopathy of renal significance and patients with B-cell malignancies. Pathology patterns like proliferative glomerulonephritis with monoclonal immunoglobulin deposits, membranous nephropathy, C3 glomerulopathy, cryoglobulinemic glomerulonephritis, and combinations of light chain proximal tubulopathy with monoclonal immunoglobulin deposition disease, and of C3 glomerulopathy with light chain proximal tubulopathy were found in monoclonal gammopathy of renal significance setting only. In contrast, light chain proximal tubulopathy alone, anti-glomerular basement glomerulonephritis, and combinations of cast nephropathy with light chain proximal tubulopathy, and cast nephropathy with monoclonal immunoglobulin deposition disease were associated with multiple myeloma only. Monoclonal immunoglobulin deposition disease, intracapillary monoclonal immunoglobulin M deposits, and cast nephropathy alone were seen in both settings.Conclusion:The presence of monoclonal gammopathy in patients with proteinuria and/or impaired kidney function demands kidney biopsy. Neither duration of kidney disease nor its clinical presentation allows differentiating malignant and non-malignant causes of monoclonal immunoglobulin–mediated renal damage. Several pathology patterns, even cast nephropathy, can be found both in cases of monoclonal gammopathy of renal significance and in cases of B-cell malignancies. Dual patterns of damage, including combinations of organized and non-organized deposits, or organized deposits with monoclonal immunoglobulin–induced damage without monoclonal immunoglobulin deposition, constitute up to 9%, mostly in multiple myeloma cases.

Ocular findings in patients with novel A/H1N1 infection: an observational cross-sectional study

Background: The systemic findings of novel A (H1N1) influenza have been well documented but data on ocular lesions is scarce. We report the systemic and ophthalmoscopic findings of 14 patients with proven H1N1 infection. Methods: An observational non-interventional retrospective study. During a period of nine years, 14 patients (six female and eight males), were referred for an ophthalmic evaluation. All patients underwent a detailed systemic and ocular evaluation. Results: Three patients (21.4 %) showed ocular lesions in the form of a unilateral intraretinal hemorrhage. Of these, one patient (7.1%) had a large disc hemorrhage and an area of retinal whitening, consistent with ischemia in the macular area. Conclusions: Physicians dealing with H1N1 infection should be aware of these findings and may include an ocular evaluation as part of their protocol.

Non-Interventional Retrospective Multicenter Study Evaluating Real Word Idelalisib Use in Chronic Lymphocytic Leukemia and Indolent Non-Hodgkin Lymphoma Patients Enrolled in the French Early Access Program

INTRODUCTIONIdelalisib (IDELA), the first-in-class PI3K-delta inhibitor, is indicated in Europe in combination with rituximab (R) or ofatumumab for the treatment (tt) of adult patients (pts) with chronic lymphocytic leukemia (CLL) who have received at least one prior therapy, or as first-line tt of pts with 17p deletion (del(17p)) or TP53 mutation (TP53m), not eligibles for any other therapies and as monotherapy for pts with follicular lymphoma (FL) refractory to two prior lines of tt. IDELA has significant clinical activity with a manageable safety profile. However, there is a paucity of real word data regarding its effectiveness and safety. The REALIST study was initiated to better describe pts who started IDELA treatment during the French Early Access Program (EAP).AIMSThe aim of this retrospective multicenter study was to describe efficacy, adverse events (AEs), serious AEs (SAEs), AEs of special interest (AESIs, defined as diarrhea/colitis, pneumonitis, liver enzyme elevation, neutropenia, infection, and rash) and IDELA use in adult pts previously enrolled in the French EAP for CLL or iNHL.METHODSAll Investigators who enrolled at least one pt in the EAP were contacted by email inviting them to participate in this study. Only pts who initiated IDELA tt between June and October 2014 have been included in this study. For each pt, 12 months (m) follow up data were collected via an electronic Case Report Form and monitored by the Lymphoma Academic Research Organization (LYSARC). The Primary endpoint was the overall response rate (ORR) at 6 m and its 95% confidence interval (95% CI). Statistical analysis was descriptive.RESULTSSeventy-five pts were included, 41 in CLL group (39 in third-line or late and 2 in first-line with del(17p)/TP53m unsuitable for chemo-immunotherapy (CIT)) and 34 in iNHL group, all refractory after two prior lines of tt. Table 1 lists key pt characteristics at the time of initiation of IDELA. In CLL/iNHL groups respectively, median IDELA tt duration was 25.1 weeks/18.9 weeks, ORR, was 82.8%/56.5% at 6 m (data reported in 29 pts/23 pts) and 100%/57.1% at 12 m (data reported in 12 pts/14 pts), median PFS was not reached (NR)/ 6.7 m, median time to next tt (TTNT) defined as the time between the date of the last IDELA intake and the start of next tt after progression of disease (PD) was NR/11.6 m, median OS was NR in both groups and OS estimate at M12 was 69.9%/67.6%. Additional efficacy data are presented in Table 2, Fig 1 and Fig 2. In CLL/iNHL groups respectively, at least one AE was reported during the study in 35 pts (85.4%)/26 pts (76.5%), most frequently reported AEs by SOC/PT were: infections and infestations 61.0%/50.0% (pneumocystis jirovecii pneumonia (PJP) 2.4%/5.9%), gastrointestinal disorders 56.1%/35.3% (diarrhea 41.5%/29.4%), blood and lymphatic system disorders 41.5%/41.2% (neutropenia 17.1%/23.5%) and investigation 43.9%/47.1% (hepatic enzyme increase 19.5%/14.7%). 24 pts (58.5%)/15 pts (44.1%) discontinued temporary IDELA, 6 pts (14.6%)/8 pts (23.5%) discontinued permanently for AE, 38 pts (92.7%)/25 pts (73.5%) had at least one AESI, 10 pts (24.4%)/11 pts (32.4%) had at least one serious AESI, 3 pts (7.3%)/6 pts (17.6%) permanently discontinued IDELA for AESI and deaths were reported during the study in 13 pts (31.7%)/11 pts (32.4%), mainly due to PD (46.2%/72.7%).CONCLUSIONThe results of this non-Interventional study of heavily pretreated CLL and iNHL population treated by IDELA monotherapy or in combination with rituximab indicate that IDELA is an effective treatment in routine clinical practice with an acceptable safety profile. ORR at 6 months was 83% in CLL full analysis set and 79% in del(17p)/TP53m sub-group and 55% in FL sub group. These results mirror those of clinical trials. No unexpected IDELA safety information was identified in this study and the pattern of AEs corresponds to that reported in previous clinical studies and might be improved by specific management of AESI including PJP prophylaxis to be administered to all patients throughout IDELA treatment. DisclosuresYsebaert:Roche: Consultancy, Research Funding; Gilead Sciences, Inc.: Consultancy, Research Funding; Janssen: Consultancy, Research Funding. Feugier:Gilead: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Roche: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Abbvie: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Janssen: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding. Salles:Novartis: Consultancy, Honoraria; Roche: Honoraria, Research Funding; Celgene: Honoraria, Research Funding; Abbvie: Honoraria; Acerta: Honoraria; Amgen: Honoraria; Epizyme: Honoraria; Gilead Sciences: Honoraria; Janssen: Honoraria; Merck: Honoraria; Morphosys: Honoraria; Pfizer: Honoraria; Servier: Honoraria; Takeda: Honoraria. Sylvain:Gilead: Other: scientific advisor board. Glorian Kergaravat:Gilead Sciences: Employment. Simpson:Gilead Sciences: Employment. Ramroth:Gilead Sciences: Employment. Abdelhadi:Gilead Sciences: Employment. Haioun:Takeda: Consultancy, Honoraria; Amgen: Consultancy, Honoraria; Gilead Sciences: Consultancy, Honoraria; Janssen: Consultancy, Honoraria; Sciences: Consultancy, Honoraria; Celgene: Consultancy, Honoraria; Roche: Consultancy, Honoraria. Troussard:Gilead: Other: scientific advisory board.

Interim Analysis Results from an International, Multi-Centre, Non-Interventional Retrospective Study to Describe Treatment Pathways, Outcomes, and Resource Use in Patients with Classical Hodgkin Lymphoma: B-CD30+ Hodgkin Lymphoma International Multi-Centre Retrospective Study of Treatment Practices and Outcomes (B-HOLISTIC)

Interim Analysis Results from an International, Multi-Centre, Non-Interventional Retrospective Study to Describe Treatment Pathways, Outcomes, and Resource Use in Patients with Classical Hodgkin Lymphoma: B-CD30+ Hodgkin Lymphoma International Multi-Centre Retrospective Study of Treatment Practices and Outcomes (B-HOLISTIC)

A COST OF ILLNESS STUDY OF TYPE 2 DIABETES MELLITUS IN MANGALORE, KARNATAKA, INDIA

Objective: The aim of the study was to study the cost of illness of uncomplicated and complicated type 2 diabetes mellitus.Methods: The non-interventional retrospective study was carried out in K.S. Hegde Medical Academy. Annual laboratory costs, pharmacy cost, consultation charges, hospital bed charges, and surgical/intervention costs of 340 diabetic patients were obtained from the medical record section of the hospital. Patients were divided into six groups, uncomplicated, diabetic retinopathy (DR), nephropathy, neuropathy, diabetic foot (DF), and those with ischemic heart disease (IHD) and different costs were compared. Correlation of costs with duration of the study and glycemic control were studied.Results: Uncomplicated patients had significantly lower costs (p<0.0001) compared to other groups. Patients with IHD had highest expenses (p<0.0001), followed by diabetic nephropathy (DN) and DF (p<0.0001). Cost incurred in diabetic neuropathy (DNeu) was almost the double compared to uncomplicated group, but annual medical cost (AMC) was minimum among other diabetic complications. DR had higher expenses compared to DNeu. The similar pattern of distribution was observed in other individual costs. A positive correlation was observed between the costs incurred and duration of diabetes, a negative correlation between the glycemic status and cost incurred. Cost incurred was double when compared to that of previous decade.Conclusion: The total AMC is significantly higher in complicated diabetic patients as compared to those without complications. Diabetic patients with IHD had the highest expenses, followed by DN, DF, DR, and DNeu which was least expensive.

An epidemiological study on the course of disease and therapeutic considerations in relapsing-remitting multiple sclerosis patients receiving injectable first-line disease-modifying therapies in Germany (EPIDEM).

Background:In relapsing–remitting multiple sclerosis (RRMS), ‘no evidence of disease activity’ (NEDA) is regarded as a key treatment goal. The increasing number of treatments allows for individualized treatment optimization in patients with suboptimal response to first-line disease-modifying therapies (DMTs). Therefore, monitoring of clinical and subclinical disease activity on DMTs has been recognized as an important component of long-term patient management.Methods:EPIDEM was a multicenter non-interventional retrospective study in a large cohort of RRMS patients receiving injectable DMTs for at least 2 years in outpatient centers throughout Germany. It documented measures and ratings of disease activity on DMTs to characterize the factors that made the treating neurologists consider to switch therapy towards potentially more effective or better-tolerated drugs.Results:The cohort included predominantly female patients with a mean age of 45 years and a mean disease duration of 9.6 years, who had been continuously treated with an injectable DMT for a median duration of 54 months. Overall, 34.0% of the patients had experienced ⩾1 relapse on any DMT in the previous 2 years; 21.0% exhibited magnetic resonance imaging (MRI) activity, and the Kurtzke Expanded Disability Status Scale (EDSS) score increased by at least 0.5 points in 20.1%. Overall, 50.3% of the patients with EDSS progression and 70.6% of the patients with relapses were assessed as clinically stable by the neurologists. A change of treatment was considered in a fraction of patients with disease activity: in 22.8% of those with relapse activity, in 37.8% of those with MRI activity and in 20.1% of those with EDSS progression.Conclusion:The results of EPIDEM underline the importance of standardized evaluation and documentation of ongoing disease activity and disability deterioration. Judged from the present data, the current paradigm of low tolerance for disease activity and recommendations for early treatment optimization have not been turned fully into action as yet. More widespread implementation of current guideline recommendations may allow patients to more benefit from the growing panel of effective treatment options.

A non-interventional retrospective cohort study of the interaction between methotrexate and proton pump inhibitors or aspirin

Methotrexate (MTX) is an antifolate drug, which is frequently used in the treatment of cancer. Proton pump inhibitors (PPIs) could delay the elimination of plasma MTX in high-dose MTX therapy by inhibition of tubular secretion, which could lead to MTX toxicity. However, the evidence of the clinical relevance of this drug-drug interaction is inconsistent. No previous studies into the effect of low dose aspirin on the elimination of MTX in high-dose therapy have been performed. Therefore, we evaluated the interaction between MTX and PPIs or aspirin. We conducted a non-interventional retrospective cohort study in patients treated with high dose MTX (≥500mg/m2 or >1000mg), between 2009 and 2016 at the OLVG ("Onze Lieve Vrouwe Gasthuis, Oost") in Amsterdam, the Netherlands. Patients were included if MTX concentrations were determined at 24, 48 or 72hours after high dose MTX treatment. We categorised the cycles of high dose MTX therapy into delayed elimination or normal elimination. Differences in patient characteristics and MTX dosing regimen were compared between all groups by X2-test, Fisher's exact probability test or Mann-Whitney U-test. In total, 89 high dose MTX cycles were included. Delayed MTX elimination was observed in 27 (30.3%) cycles. Co-administration of a PPI was significantly more frequent in the delayed elimination group than in the normal elimination group (P<0.001). There was no statistical effect observed by co-administration of aspirin. The use of PPIs during high dose MTX treatment can lead to delayed MTX elimination. Discontinuation of PPIs during high dose MTX treatment is recommended. Co-administration of aspirin did not influence the elimination of MTX, but further research is needed.

Identification of patients at risk of non-adherence to oral antirheumatic drugs in rheumatoid arthritis using the Compliance Questionnaire in Rheumatology: an ARCO sub-study

The ARCO study (Study on Adherence of Rheumatoid Arthritis patients to SubCutaneous and Oral Drugs), a multicenter, non-interventional retrospective study, was primarily designed to assess the percentage of patients [aged ≥18years with an established rheumatoid arthritis (RA) diagnosis] with non-adherence to prescribed subcutaneous biologicals. This paper reports data for the secondary objective from a subset of patients, namely to evaluate non-adherence to prescribed oral antirheumatic drugs in RA patients in Spain using the validated Compliance Questionnaire Rheumatology (CQR). Patients also completed the Morisky-Green Medication Adherence Questionnaire, Beliefs about Medicines Questionnaire, and a questionnaire (developed and validated in Spain) on patient satisfaction with RA treatment and preferences. A total of 271 patients (76.7% females; mean age 55.6years) were being treated with oral drugs for RA, of which 234 completed the CQR questionnaire. Non-adherence was reported in 49/234 (20.9%) patients. The proportion of non-adherence in younger patients (aged ≤48years; 37.5%) was double that recorded in patients aged >48years (p=0.006). Patients with a perception of lower efficacy also had a higher risk of non-adherence (p=0.012). Multivariable analysis showed that younger age and male gender were independently associated with risk of non-adherence. There was only slight agreement between the CQR and Morisky-Green assessment tools (kappa coefficient=0.186), possibly reflecting the fact that both questionnaires measure slightly different aspects of medication adherence. In conclusion, one out of five RA patients was identified as at risk for non-adherence with the CQR, and this was more frequent in younger patients and in males.

&amp;lt;i&amp;gt;In Vivo&amp;lt;/i&amp;gt; Emulsification Analysis of 1000 cs and 5000 cs Silicone Oil after Rhegmatogenous Retinal Detachment Vitrectomy Surgery

Purpose: To compare in vivo emulsification of silicone oil 1000 and 5000 centistokes (cs) after retinal detachment surgery. Design: Comparative non-interventional Retrospective study. Methods: Silicone oils from patients who underwent retinal detachment surgery were investigated using Spectrophotometer UV-Vis. Spectroscopically changes determine emulsification with the time of tamponade, inflammation, patients age and severity of retinal detachment. Results: We found significant difference on absorbance (p = 0.004) between used 1000 Centi stoke (cs) silicon oil (average wave length 2.51 nm; SD: 1.575 nm) and used 5000 cs silicon oil (average wave length 0.910 nm; SD: 0.564 nm). Conclusions: In vivo emulsification was higher in silicone oil 1000 compared to 5000 cs silicone oil after vitreoretinal tamponade 8 - 12 weeks due to retinal detachment surgery. Emulsification related to higher absorbance and lower transmittance in 1000 cs silicone oil. Inflammation may become a factor affecting this condition.

The Cost of Managing Type 2 Diabetes Mellitus in Greece: A Retrospective Analysis of 10-Year Patient Level Data "The HERCULES Study".

Objective. This study aimed to estimate the mean annual cost of treating type 2 diabetes mellitus patients (T2DM) including complications and comorbidities in Greece. Design. A noninterventional retrospective study was based on patient level data analysis (bottom-up approach) from medical records, with at least 10-year-follow-up data. Results. The total annual cost per patient for managing diabetes in Greece was estimated at € 7,111 and was, statistically significantly, higher for patients with inadequate glycemic control (Hba1c > 7%) versus patients with adequate control (Hba1c = 7%) (€ 7,783 versus € 6,366, resp.; P = 0.017). This was mainly attributed to difference in CV hospitalizations between groups 14/111 versus 4/100, respectively, OR = 3.46 (95% CI: 1.10–10.9) for inadequately controlled patients. The largest component of cost was management of comorbidities, accounting for 48% of costs, and pharmaceutical treatment at 35.9% while only 14.9% was attributed to diabetes treatment per se. Obese men and patients with poor education are the groups with higher treatment costs. Conclusions. This is the first study to capture all cost components and the real burden of diabetes in Greece. Comorbidities were found to account for almost half of total cost, significantly higher in nonoptimally controlled diabetes patients.

Efficacy and Safety of Sequential Use of Everolimus in Patients With Metastatic Renal Cell Carcinoma Previously Treated With Bevacizumab With or Without Interferon Therapy: Results From the European AVATOR Study

BackgroundEverolimus is a mammalian target of rapamycin (mTOR) inhibitor. It gained approval based on the results of the RECORD-1 (Regulation of Coagulation in Orthopedic Surgery to Prevent Deep Venous Thrombosis and Pulmonary Embolism 1) trial, which included patients with metastatic renal cell carcinoma (mRCC) whose disease progressed after receiving vascular endothelial growth factor receptor (VEGFR) tyrosine kinase inhibitors (TKIs). Bevacizumab is a monoclonal antibody targeting angiogenesis that is approved in patients with mRCC. The sequence of everolimus second-line therapy after failure of bevacizumab ± interferon (IFN) first-line therapy has not yet been studied. MethodsAVAstin® followed by afiniTOR® (AVATOR) was a noninterventional retrospective multicenter European observational study of 42 unselected patients with mRCC who were previously or currently treated with everolimus after failure of bevacizumab ± IFN. The primary end point was everolimus progression-free survival (PFS). Secondary end points were related to the overall survival (OS) of patients receiving the drug sequence and everolimus treatment and safety. ResultsExploring the duration of second-line everolimus treatment, 63.8% of patients received at least 3 months of everolimus and 28.8% received at least 8 months of treatment. At the time of data analysis, 15 patients (36%) were still receiving everolimus, 40% had stopped because of progressive disease, and 24% had discontinued treatment for other reasons. Patients receiving everolimus after bevacizumab experienced a median PFS of 17 months (95% confidence interval [CI], 5 [not reached]). Median OS was not reached with everolimus second-line therapy. At 32 months after the start of first-line therapy, 53.3% of patients were still alive. All grades of common adverse events (AEs) were consistent with the known safety profile of everolimus. ConclusionThe AVATOR-studied sequence displayed a longer than expected median PFS. Further prospective exploratory studies need to be performed to confirm these encouraging results in a larger cohort of patients.

P18.08 * A MULTICENTRIC, OBSERVATIONAL, NON INTERVENTIONAL STUDY OF EFFICACY AND SAFETY OF LACOSAMIDE FOR THE TREATMENT OF EPILEPTIC SEIZURES IN PATIENTS WITH BRAIN TUMORS

INTRODUCTION: Epileptic seizures are common in oncologic patients. Seizures could be the initial symptom of a brain tumor in 20-40% of the cases and 40% of the patients with brain tumors will have a seizure throught the diseqse. Management of these complications is crucial in the treatment of brain tumors. The ideal antiepileptic drug (AED) would be that one which could ensure a high and proved efficacy, wide security, low interactions, easy and quick to titrate and available in i.v. formulation. Until today there is a scarce number of publications on the use of lacosamide (LCM) in patients with btain tumors, although there is some experience in routine clinical practice that has previously shown a very promising profile of efficacy and safety. This study tries to compile some of these experiences in Spain. OBJECTIVES: To evaluate the efficacy of LCM in the management of seizures in patients with brain tumors. Secondary objectives were the evaluation of safety and tolerability of LCM . DESIGN: Multicentric, observational, non-interventional retrospective study. Patients who suffered at least 1 convulsive episode and at least treated with 1 dose of LCM were recruited. RESULTS: 37 patients with brain tumor suffering seizures were recruited in 6 centers all over the country, and 24 of them (64.9%) could be followed-up until the end of the study (after 6 months). Of these 37 patients, 26 (70%) were male, the age was 54.14 ± 14 years. 28 patients had one lesion and 9 had several lesions, 7 of them were metastatic. The average of total number of seizures from the onset of LCM treatment to the last visit performed shows a statistically significant change from the initiation of LCM treatment, showing a reduction of -16.8 ± 41'7 seizures. (p <000.1) The reason for withdrawing from the study was death by cancer in 7 of all the 37 initially included (53.85%), being a lack of LCM efficacy in 2 patients. A total of 12 more patients needed a LCM modification of treatment, 9 due to lack of efficacy, 3 due to adverse events. CONCLUSIONS: In a retrospective, non-interventional study with brain tumor patients, LCM has shown to be effective and safe in the management of seizures in neurooncological patients.

Prognostic factors of early death in a cohort of 162 adult haemophagocytic syndrome: impact of triggering disease and early treatment with etoposide.

Reactive haemophagocytic syndrome is a life-threatening disease for which factors influencing the outcome remain unclear. We sought to identify determinants of early mortality in patients with reactive haemophagocytic syndrome by conducting a non-interventional retrospective multicentre study in three tertiary care teaching hospitals over a 6-year period. The medical files of 162 patients fulfilling our diagnostic criteria of haemophagocytic syndrome were reviewed. Patients were classified according to 30-d outcome following diagnosis. Thirty-three patients (20·4%) died within 30 d. Clinical features at diagnosis associated with 30-d death in univariate analysis were older age (P = 0·004), underlying lymphoma (P = 0·04), lower platelet count (P = 0·001) and elevated aspartate aminotransferase and lactate dehydrogenase (P = 0·04 both). The use of etoposide as a first-line treatment tended to be associated with a better outcome (P = 0·079). In multivariate analyses, increasing age, decreasing platelet count, underlying lymphoma and no etoposide in the management were associated with a poorer prognosis (P = 0·03, 0·01, 0·003 and 0·04, respectively). These prognostic factors could help to identify those patients more severely affected by reactive haemophagocytic syndrome, who should benefit from aggressive supportive care, combined with specific treatment of the precipitating factor.