Abstract 14733: Influence of High Risk Adrenergic Receptor Genotypes on Outcome in Infants With Single Ventricle

Circulation ◽  
2015 ◽  
Vol 132 (suppl_3) ◽  
Author(s):  
Ronand Ramroop ◽  
Dorin Manase ◽  
George Manase ◽  
Cory Simmons ◽  
Jane W Newburger ◽  
...  
Keyword(s):  
Adverse Events ◽  
Clinical Outcomes ◽  
Confidence Intervals ◽  
Adrenergic Receptor ◽  
Single Ventricle ◽  
Adverse Outcomes ◽  
Hospital Length Of Stay ◽  
Serious Adverse Events ◽  
Free Survival

Introduction: Variants in adrenergic receptor (ADR) genes are associated with adverse clinical outcomes in patients with heart failure. We evaluated the association of variants in ADR receptor genes with outcomes in infants with single ventricle lesions. Methods: Infants with single ventricle lesions participating in the Pediatric Heart Network Single Ventricle Reconstruction Trial (randomized to Norwood with modified Blalock-Taussig shunt versus right ventricle-pulmonary artery shunt) underwent genotyping for 4 single nucleotide polymorphisms (SNPs) in 3 ADR genes: ADRB1-A/G (rs1801252), ADRB1-C/G (rs1801253), ADRB2-C/G (rs1042714) and ADRA2A-C/T (rs553668). Linear and logistic regression, deviance tests, t-tests and F-tests were used to analyze association of genotype with clinical outcomes including hospital length of stay (LOS) at Norwood, occurrence of serious adverse events (SAE), and transplant-free survival during 14 months follow-up using a dominant model. Results: The study included 347 eligible patients (62% male; 83% white). The mean age at Norwood procedure was 6±3.6 days and median Norwood LOS was 8 days. During 14 months follow-up, 147 patients had SAEs, 94 patients died and 14 were transplanted. ADRB1 AA (rs1801252) genotype was associated with longer Norwood LOS. The difference in LOS between AA vs AG/GG was 7.99 days (confidence intervals, 0.27, 15.71; p=0.043). ADRA2A CC (rs553668) genotype was associated with higher odds of SAEs i.e. 103/216 (47.6%) in CC compared to 36/106 (34%) in CT/TT [Odds ratio 1.77 (confidence intervals, 1.09, 2.87), p=0.018]. Transplant-free survival was not different between genotype groups. Combined analysis of risk genotypes did not confer an additive risk of adverse outcomes. Conclusions: ADR genotypes known to cause adrenergic upregulation were associated with prolonged Norwood hospitalization and/or serious adverse events in infant single ventricles. This may be secondary to adverse effects of adrenergic overexpression on cardiac function and systemic hemodynamics. Analysis is ongoing to replicate these findings for utility as predictive markers for outcomes in infant single ventricles.

Adjuvant nivolumab in high-risk stage IIb/IIc melanoma patients: Results from investigator initiated clinical trial.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. 9583-9583
Author(s):  
Melissa Wilson ◽  
Larisa J. Geskin ◽  
Richard D. Carvajal ◽  
Janice M. Mehnert ◽  
Cody Chiuzan ◽  
...  
Keyword(s):  
Clinical Trial ◽  
Overall Survival ◽  
High Risk ◽  
Adverse Events ◽  
High Dose ◽  
Serious Adverse Events ◽  
Free Survival ◽  
Immune Correlates ◽  
Melanoma Patients

9583 Background: Recent studies have shown 5-yr recurrence rates for Stage IIB and IIC melanoma of up to 46%. These high-risk patients currently have few options for adjuvant therapy to prevent this inevitable recurrence, with the only FDA approved therapy being high-dose interferon-alfa, which is quite toxic. However, there are now immunotherapies (anti-PD1) and targeted therapies (anti-BRAF and anti-MEK combinations) which are approved as adjuvants for Stage III patients, some of whom will have a lower baseline recurrence risk than those with Stage IIB/IIC melanoma. We sought to determine if adjuvant PD1 inhibition with nivolumab (N) would improve the recurrence free survival (RFS) compared to historical RFS rates. Methods: Our study (NCT03405155) is a single-arm, open label, multi-center, phase 2 clinical trial evaluating RFS at 24 months in patients with Stage IIB/IIC melanoma on treatment with N at 480 mg IV every 4 weeks for 12 cycles. Overall survival is a secondary endpoint. Associated translational research includes circulating tumor cell DNA and immune correlates. Results: Twenty three patients with Stage IIB and three patients with Stage IIC melanoma were enrolled onto the study and received at least one dose of N. At data cutoff, 22 patients remain in follow up, as four patients withdrew consent at different time points in the study – one patient after one dose who wished to discontinue, one due to concern for COVID and need for repeat visits, one due to insurance issues, and one due to recurrence and wish to discontinue (which was captured in study data and RFS calculations). Seventeen patients have been on the clinical trial for at least two years with nine patients having finished treatment but with less than two years follow-up; the median follow-up is currently 21.9 months. Two patients demonstrated melanoma recurrence, one after receiving cycle six of N and another one year after completing treatment, resulting in a 87.8% RFS (90% CI (64.2%-96.3%) at 2 years, compared to the historical RFS at 2 years of 70%. No N related serious adverse events (SAEs) were observed, with only 2% Grade 3 AEs observed (varied and unrelated to treatment) and all others were Grade 1-2, including 21% GI, 18% cutaneous, and 10% musculoskeletal, respiratory, and fatigue, each; overall, 2% of these Grade 1-2 AEs were treatment related. Conclusions: Our preliminary results show a trend towards improved RFS in patients with Stage IIB/IIC melanoma treated with nivolumab. The cohort has not reached a minimum follow up of at least 2 years for RFS; patients are continuing to be monitored. On study, we observed the expected adverse events, without evidence of new toxicities. Data maturation will reveal the full effect of adjuvant N on disease relapse and overall survival and distant metastasis-free survival in stage IIB/IIC melanoma patients. Clinical trial information: NCT03405155.

EXPRESS: Altering the rehabilitation environment to improve stroke survivor activity (AREISSA): a Phase II trial.

2021 ◽  
pp. 174749302110069
Author(s):  
Heidi Janssen ◽  
Louise Ada ◽  
Sandy Middleton ◽  
Michael Pollack ◽  
Michael Nilsson ◽  
...  
Keyword(s):  
Adverse Events ◽  
Clinical Outcomes ◽  
Environmental Enrichment ◽  
Brain Plasticity ◽  
Social Activity ◽  
Stroke Survivor ◽  
Group Differences ◽  
Control Group ◽  
Serious Adverse Events ◽  
Clinical Trial Registration

Background: Environmental enrichment involves organisation of the environment and provision of equipment to facilitate engagement in physical, cognitive and social activity. In animals with stroke, it promotes brain plasticity and recovery. Aims: To assess the feasibility and safety of a patient-driven model of environmental enrichment incorporating access to communal and individual environmental enrichment. Methods: A non-randomised cluster trial with blinded measurement involving people with stroke (n=193) in 4 rehabilitation units was carried out. Feasibility was operationalised as activity 10 days after admission to rehabilitation and availability of environmental enrichment. Safety was measured as falls and serious adverse events. Benefit was measured as clinical outcomes at 3 months, by an assessor blinded to group. Results: The experimental group (n=91) spent 7% (95% CI -14 to 0) less time inactive, 9% (95% CI 0 to 19) more time physically, and 6% (95% CI 2 to 10) more time socially active than the control group (n=102). Communal environmental enrichment was available 100% of the time, but individual environmental enrichment was rarely within reach (24%) or sight (39%). There were no between-group differences in serious adverse events or falls at discharge or 3 months nor in clinical outcomes at 3 months. Conclusions: This patient-driven model of environmental enrichment was feasible and safe. However, the very modest increase in activity by people with stroke, and the lack of benefit in clinical outcomes 3 months after stroke do not provide justification for an efficacy trial. Clinical Trial Registration: ANZCTR 12613000796785 Words: 245

scholarly journals Bioabsorbable Implant for Treatment of Nasal Valve Collapse with or without Concomitant Procedures

2021 ◽  
Author(s):  
Douglas M. Sidle ◽  
Pablo Stolovitzky ◽  
Ellen M. O'Malley ◽  
Randall A. Ow ◽  
Nathan E. Nachlas ◽  
...  
Keyword(s):  
Adverse Events ◽  
Nasal Obstruction ◽  
Large Population ◽  
Inferior Turbinate ◽  
Nasal Valve ◽  
Serious Adverse Events ◽  
Vas Scores ◽  
Nasal Implant ◽  
Nasal Valve Collapse

AbstractThe aim of the study is to report outcomes after treatment of nasal valve collapse with a bioabsorbable nasal implant. It involves two prospective, multicenter, post-market studies evaluating long-term effectiveness of the LATERA implant for severe to extreme nasal obstruction. Participants underwent implant alone or with concomitant inferior turbinate reduction (ITR) and/or septoplasty. Outcome measures included the change from baseline Nasal Obstruction Symptom Evaluation (NOSE) scores, NOSE responder rates, visual analog scale (VAS) scores, and adverse events. A total cohort of 277 participants (109 implants only, 67 implants + ITR, 101 implants + septoplasty + ITR) enrolled at 19 U.S. centers was available for analysis with 177 participants (69 implants only, 39 implants + ITR, 69 implants + septoplasty + ITR) available at 2 years. The mean changes from baseline in NOSE scores and VAS scores were statistically significant (p < 0.001) at all follow-up periods. The baseline NOSE score of 77.8 ± 13.6 was improved to 24.2 ± 23.6 at 24 months. Greater than 90% of participants were NOSE responders across all follow-up periods, 6.1% withdrew for lack of treatment effect. The baseline VAS score of 66.7 ± 18.8 was improved to 21.1 ± 23.9 at 24 months. There were no serious adverse events related to the device or implant procedure. Implant retrieval rate was 4.0% (22/543 implants). Nonserious adverse events were mild to moderate in severity, typically occurred within 6 months of implant, and resolved or were stable. Significant reductions in NOSE and VAS scores and high responder rates from our large population of patients with nasal obstruction who had nasal valve implants confirm sustained effectiveness at 24 months after treatment. The studies are registered on www.clinicaltrials.gov (NCT02952313 and NCT02964312).

scholarly journals POS0815 CLINICAL CHARACTERISTICS, IMAGING PHENOTYPE, AND LONG-TERM OUTCOMES OF TAKAYASU ARTERITIS PATIENTS WITH HYPERTENSION

2021 ◽  
Vol 80 (Suppl 1) ◽  
pp. 661.1-661
Author(s):  
Y. Sun ◽  
L. Ma ◽  
H. Chen ◽  
C. Rongyi ◽  
L. Jiang
Keyword(s):  
Blood Pressure ◽  
Adverse Events ◽  
Clinical Features ◽  
Takayasu Arteritis ◽  
Pressure Control ◽  
Free Survival ◽  
The World ◽  
Cluster 2

Background:Hypertension occurred in 30-80% of TAK patients around the world. The occurrence of hypertension might severely worsen TAK prognosis. Nevertheless, data describing the specific imaging features in hypertensive TAK patients and the associations between hypertensive severity, blood pressure control status and long-term outcome were still lacking.Objectives:To investigate the characteristics and associations of hypertensive characteristics with adverse events-free survival in Takayasu arteritis (TAK) patients with hypertension.Methods:This research was based on a prospectively on-going observational cohort-East China Takayasu Arteritis (ECTA) cohort. In all, 618 TAK patients, who registered in the ECTA cohort up to December 2019, were enrolled. The main outcome was the adverse-events-free survival among hypertensive TAK patients during the follow-up ended on August 2020.Results:Totally, 204 (33.0%) patients suffered from hypertension, with 48 (23.5%), 62 (30.4%), and 94 (46.1%) mild, moderate, and severe hypertension, respectively. Cluster analysis indicated three imaging phenotypes for hypertensive TAK patients: Cluster 1: involvement of the abdominal aorta and/or renal artery (n=56, 27.5%); Cluster 2: involvement of the ascending aorta, thoracic aorta, and the aortic arch and its branches (n=38, 18.6%); Cluster 3: combined involvement of Cluster 1 and Cluster 2 (n=111, 54.4%). By the end of the follow-up, the blood pressure control rate was 50.8%, while the adverse-events-free survival was 67.9% in the entire hypertensive population. Multivariate Cox regression analysis indicated that well-controlled blood pressure (HR=2.13, 95%CI 1.32–3.78, p=0.047), co-existence of severe aortic valve regurgitation (HR=0.87, 95%CI 0.64–0.95, p=0.043), Cluster 1 (HR=0.69, 95%CI 0.48–0.92, p=0.017) and Cluster 3 (HR=0.72, 95%CI 0.43–0.94, p=0.048) imaging phenotype was associated with the adverse-events-free survival.Conclusion:Patients with controlled hypertension showed better adverse-events-free survival, while those with the Cluster 1 imaging phenotype were more likely to suffer from worse adverse-events-free survival. Hypertension occurred in 30-80% of TAK patients around the world. The occurrence of hypertension might severely worsen TAK prognosis.References:[1]Johnston SL, Lock RJ, Gompels MM. Takayasu arteritis: a review. J Clin Pathol 2002; 55:481–6.[2]Watanabe Y, Miyata T, Tanemoto K. Current clinical features of new patients with Takayasu arteritis observed from a cross-country research in Japan: age and sex specificity. Circulation 2015; 132:1701–9.[3]Yilmaz N, Can M, Oner FA, et al. Impaired quality of life, disability and mental health in Takayasu’s arteritis. Rheumatol. (Oxford) 2013; 52:1898–904.[4]Laurent A, Julien H, Nicolas L, et al. Takayasu arteritis in France: a single-center retrospective study of 82 cases comparing white, North African, and black patients. Medicine 2010; 89:1–17.[5]Mwipatayi BP, Jeffery PC, Beningfield SJ, et al. Takayasu arteritis: clinical features and management: report of 272 cases. ANZ J Surg 2005; 75:110–7.Disclosure of Interests:None declared

scholarly journals POS0647 EFFICACY, SAFETY AND CHARACTERISTICS OF IGURATIMOD-BASED THERAPY IN THE TREATMENT OF UA, ERA AND RA PATIENTS FOR 24 WEEKS: A PROSPECTIVE COHORT STUDY

2021 ◽  
Vol 80 (Suppl 1) ◽  
pp. 561.2-562
Author(s):  
X. Liu ◽  
Z. Sun ◽  
W. Guo ◽  
F. Wang ◽  
L. Song ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Cohort Study ◽  
Adverse Events ◽  
Disease Activity ◽  
Prospective Cohort Study ◽  
Early Rheumatoid Arthritis ◽  
Prospective Cohort ◽  
Combined Treatment ◽  
Serious Adverse Events

Background:Experts emphasize early diagnosis and treatment in RA, but the widely used diagnostic criterias fail to meet the accurate judgment of early rheumatoid arthritis. In 2012, Professor Zhanguo Li took the lead in establishing ERA “Chinese standard”, and its sensitivity and accuracy have been recognized by peers. However, the optimal first-line treatment of patients (pts) with undifferentiated arthritis (UA), early rheumatoid arthritis (ERA), and rheumatoid arthritis (RA) are yet to be established.Objectives:To evaluate the efficacy and safety of Iguratimod-based (IGU-based) Strategy in the above three types of pts, and to explore the characteristics of the effects of IGU monotherapy and combined treatment.Methods:This prospective cohort study (ClinicalTrials.gov Identifier NCT01548001) was conducted in China. In this phase 4 study pts with RA (ACR 1987 criteria[1]), ERA (not match ACR 1987 criteria[1] but match ACR/EULAR 2010 criteria[2] or 2014 ERA criteria[3]), UA (not match classification criteria for ERA and RA but imaging suggests synovitis) were recruited. We applied different treatments according to the patient’s disease activity at baseline, including IGU monotherapy and combination therapies with methotrexate, hydroxychloroquine, and prednisone. Specifically, pts with LDA and fewer poor prognostic factors were entered the IGU monotherapy group (25 mg bid), and pts with high disease activity were assigned to combination groups. A Chi-square test was applied for comparison. The primary outcomes were the proportion of pts in remission (REM)or low disease activity (LDA) that is DAS28-ESR<2.6 or 3.2 at 24 weeks, as well as the proportion of pts, achieved ACR20, Boolean remission, and good or moderate EULAR response (G+M).Results:A total of 313 pts (26 pts with UA, 59 pts with ERA, and 228 pts with RA) were included in this study. Of these, 227/313 (72.5%) pts completed the 24-week follow-up. The results showed that 115/227 (50.7%), 174/227 (76.7%), 77/227 (33.9%), 179/227 (78.9%) pts achieved DAS28-ESR defined REM and LDA, ACR20, Boolean remission, G+M response, respectively. All parameters continued to decrease in all pts after treatment (Fig 1).Compared with baseline, the three highest decline indexes of disease activity at week 24 were SW28, CDAI, and T28, with an average decline rate of 73.8%, 61.4%, 58.7%, respectively. Results were similar in three cohorts.We performed a stratified analysis of which IGU treatment should be used in different cohorts. The study found that the proportion of pts with UA and ERA who used IGU monotherapy were significantly higher than those in the RA cohort. While the proportion of triple and quadruple combined use of IGU in RA pts was significantly higher than that of ERA and UA at baseline and whole-course (Fig 2).A total of 81/313 (25.8%) pts in this study had adverse events (AE) with no serious adverse events. The main adverse events were infection(25/313, 7.99%), gastrointestinal disorders(13/313, 4.15%), liver dysfunction(12/313, 3.83%) which were lower than 259/2666 (9.71%) in the previous Japanese phase IV study[4].The most common reasons of lost follow-up were: 1) discontinued after remission 25/86 (29.1%); 2) lost 22/86 (25.6%); 3) drug ineffective 19/86 (22.1%).Conclusion:Both IGU-based monotherapy and combined therapies are tolerant and effective for treating UA, ERA, and RA, while the decline in joint symptoms was most significant. Overall, IGU combination treatments were most used in RA pts, while monotherapy was predominant in ERA and UA pts.References:[1]Levin RW, et al. Scand J Rheumatol 1996, 25(5):277-281.[2]Kay J, et al. Rheumatology 2012, 51(Suppl 6):vi5-9.[3]Zhao J, et al. Clin Exp Rheumatol 2014, 32(5):667-673.[4]Mimori T, et al. Mod Rheumatol 2019, 29(2):314-323.Disclosure of Interests:None declared

scholarly journals Clinical Outcomes of Digital Cholangioscopy-Guided Procedures for the Diagnosis of Biliary Strictures and Treatment of Difficult Bile Duct Stones: A Single-Center Large Cohort Study

2021 ◽  
Vol 10 (8) ◽  
pp. 1638
Author(s):  
Hirohito Minami ◽  
Shuntaro Mukai ◽  
Atsushi Sofuni ◽  
Takayoshi Tsuchiya ◽  
Kentaro Ishii ◽  
...  
Keyword(s):  
Bile Duct ◽  
Adverse Events ◽  
Clinical Outcomes ◽  
Significant Risk ◽  
Histopathological Analysis ◽  
Bile Duct Stones ◽  
Serious Adverse Events ◽  
Visualization System ◽  
Visual Impression ◽  
Number Of Patients

Although Spy DS (SpyGlass DS Direct Visualization System) is considered to be useful for the diagnosis of bile duct strictures and the treatment of bile duct stones, there is limited data to date validating its efficacy. We hence retrospectively evaluated the clinical outcomes of the use of Spy DS in a large number of patients. A total of 183 patients who underwent Spy DS-guided procedures for indeterminate bile duct strictures (n = 93) and bile duct stones (n = 90) were analyzed retrospectively. All patients (93/93) with bile duct strictures successfully underwent visual observation, and 95.7% (89/93) of these patients successfully underwent direct biopsy. The sensitivity, specificity, and overall accuracy were 94.7%, 83.3%, and 90.3%, respectively, for visual impression; 80.9%, 100%, and 89.2%, respectively, for histopathological analysis of a direct biopsy; and 96.5%, 91.7%, and 94.6%, respectively, for visual impression combined with biopsy. Successful visualization of the stones was achieved in 98.9% (89/90) of the patients, and complete stone removal was achieved in 92.2% (83/90) of the patients, with an average of 3.3 procedures. The adverse events rate was 17.5% (32/183; cholangitis in 15 patients, fever the following day in 25, pancreatitis in 1, hemorrhage in 1, and gastrointestinal perforation in 1). No administration of antibiotics before the procedure was found to be a statistically significant risk factor for the development of fever after the procedure (p < 0.01). Spy DS-guided procedures are effective for the diagnosis and treatment of bile duct lesions and can be performed with a low risk of serious adverse events.

scholarly journals Efficacy and safety of combined endoscopic cyanoacrylate injection and balloon-occluded retrograde transvenous occlusion (BRTOcc) of gastrorenal shunts in patients with bleeding gastric fundal varices

2020 ◽  
Author(s):  
Fateh Bazerbachi ◽  
Akira Dobashi ◽  
Swarup Kumar ◽  
Sanjay Misra ◽  
Navtej S Buttar ◽  
...  
Keyword(s):  
Adverse Events ◽  
Gastric Varices ◽  
High Rate ◽  
Efficacy And Safety ◽  
Cyanoacrylate Glue ◽  
Serious Adverse Events ◽  
Gastroesophageal Varices ◽  
Life Threatening ◽  
Glue Embolization

Abstract Background Endoscopic cyanoacrylate (glue) injection of fundal varices may result in life-threatening embolic adverse events through spontaneous gastrorenal shunts (GRSs). Balloon-occluded retrograde transvenous occlusion (BRTOcc) of GRSs during cyanoacrylate injection may prevent serious systemic glue embolization through the shunt. This study aimed to evaluate the efficacy and safety of a combined endoscopic–interventional radiologic (BRTOcc) approach for the treatment of bleeding fundal varices. Methods We retrospectively analysed the data of patients who underwent the combined procedure for acutely bleeding fundal varices between January 2010 and April 2018. Data were extracted for patient demographics, clinical and endoscopic findings, technical details, and adverse events of the endoscopic–BRTOcc approach and patient outcomes. Results We identified 30 patients (13 [43.3%] women; median age 58 [range, 25–92] years) with gastroesophageal varices type 2 (53.3%, 16/30) and isolated gastric varices type 1 (46.7%, 14/30) per Sarin classification, and median clinical and endoscopic follow-up of 151 (range, 4–2,513) days and 98 (range, 3–2,373) days, respectively. The median volume of octyl-cyanoacrylate: Lipiodol injected was 7 (range, 4–22) mL. Procedure-related adverse events occurred in three (10.0%) patients, including transient fever, non-life-threatening pulmonary glue embolism, and an injection-site ulcer bleed. Complete gastric variceal obturation was achieved in 18 of 21 patients (85.7%) at endoscopic follow-up. Delayed variceal rebleeding was confirmed in one patient (3.3%) and suspected in two patients (6.7%). Although no procedure-related deaths occurred, the overall mortality rate was 46.7%, primarily from liver-disease progression and co-morbidities. Conclusion The combined endoscopic–BRTOcc procedure is a relatively safe and effective technique for bleeding fundal varices, with a high rate of variceal obturation and a low rate of serious adverse events.

637 Immune-related adverse events (irAEs) may indicate a favorable prognosis in metastatic renal cell carcinoma (mRCC) patients treated with immune checkpoint inhibitors (ICI)

2020 ◽  
Vol 8 (Suppl 3) ◽  
pp. A672-A673
Author(s):  
Dylan Martini ◽  
Sean Evans ◽  
Subir Goyal ◽  
Yuan Liu ◽  
T Anders Olsen ◽  
...  
Keyword(s):  
Renal Cell Carcinoma ◽  
Overall Survival ◽  
Adverse Events ◽  
Clinical Outcomes ◽  
Immune Checkpoint Inhibitors ◽  
Checkpoint Inhibitors ◽  
Progression Free Survival ◽  
Free Survival ◽  
Kaplan Meier ◽  
Emory University

BackgroundImmune checkpoint inhibitors (ICI) have become an increasingly utilized treatment in metastatic renal cell carcinoma (mRCC). Although they have a favorable toxicity profile, immune-related adverse events (irAEs) can have a significant impact on patients‘ quality of life. It is not well understood whether irAEs are associated with improved clinical outcomes. We investigated the relationship between irAEs and clinical outcomes in mRCC patients treated with ICI.MethodsWe performed a retrospective study of 200 patients with mRCC who received ICI at Winship Cancer Institute of Emory University from 2015–2020. Clinical outcomes were measured by overall survival (OS), progression-free survival (PFS), and clinical benefit (CB). OS and PFS were calculated from ICI-initiation to date of death and radiographic or clinical progression, respectively. CB was defined as a best radiographic response of complete response (CR), partial response (PR), or stable disease (SD) for >6 months per response evaluation criteria in solid tumors (RECIST) version 1.1. Toxicity data was collected from clinic notes and laboratory values. The association with OS and PFS was modeled by Cox proportional hazards model. Kaplan-Meier curves were created for survival estimates.ResultsMost patients were males (71%), and 78% had clear-cell RCC (ccRCC). Most patients (58%) received anti-PD-1 monotherapy. The majority were international mRCC database consortium (IMDC) intermediate (57%) or poor-risk (26%). Anti-PD-1 monotherapy was the most common (58%) treatment regimen and most patients received ICI as first (38%) or second-line (42%) treatment. One-third of patients (33%) experienced an irAE, with the most common being endocrine (13%), gastrointestinal (11%), and dermatologic (10%). Patients who experienced irAEs had significantly longer OS (HR: 0.52, 95% CI: 0.32–0.87, p=0.013), higher chance of CB (OR: 2.10, 95% CI: 1.11–4.00, p=0.023) and showed a trend towards longer PFS (HR: 0.71, 95% CI: 0.49–1.02, p=0.065) in MVA (table 1). Patients who had thyroid irAEs had significantly longer OS, PFS, and higher chance of CB in MVA (table 1). The objective response rate was higher for patients who experienced irAEs (34% vs. 18%). Patients who experienced irAEs had significantly longer median OS (44.5 vs. 18.2 months, p=0.005) and PFS (7.5 vs 3.6 months, p=0.0028) compared to patients who did not (figure 1).Abstract 637 Table 1MVA* of association between irAEs and clinical outcomesAbstract 637 Figure 1Kaplan-Meier curves of association between immune-related adverse events (irAEs) and overall survival (OS, top panel) and progression-free survival (PFS, bottom panel)ConclusionsWe showed that mRCC patients who experienced irAEs, particularly thyroid irAEs, had improved clinical outcomes. This suggests that irAEs may be prognostic of favorable outcomes in mRCC patients treated with ICI. Larger, prospective studies are needed to validate these findings.AcknowledgementsResearch reported in this publication was supported in part by the Breen Foundation and the Biostatistics Shared Resource of Winship Cancer Institute of Emory University and NIH/NCI under award number P30CA138292. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health.Trial RegistrationNot applicableEthics ApprovalThis retrospective study was approved by the Emory University Institutional Review Board.ConsentNot applicableReferencesNot applicable

scholarly journals Safety of alemtuzumab in a nationwide cohort of Finnish multiple sclerosis patients

2021 ◽  
Author(s):  
Ilkka Rauma ◽  
Tiina Mustonen ◽  
Juha Matti Seppä ◽  
Maritta Ukkonen ◽  
Marianne Männikkö ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Adverse Events ◽  
Case Series ◽  
Retrospective Case ◽  
Serious Adverse Events ◽  
Highly Active ◽  
Disease Modifying Therapy ◽  
Case Series Study ◽  
Multiple Sclerosis Patients

Abstract Background Alemtuzumab is an effective disease-modifying therapy (DMT) for highly active multiple sclerosis (MS). However, safety concerns limit its use in clinical practice. Objectives To evaluate the safety of alemtuzumab in a nationwide cohort of Finnish MS patients. Methods In this retrospective case series study, we analyzed the data of all but two MS patients who had received alemtuzumab in Finland until 2019. Data were systematically collected from patient files. Results Altogether 121 patients were identified, most of whom had received previous DMTs (82.6%). Median follow-up time after treatment initiation was 30.3 months and exceeded 24 months in 78 patients. Infusion-associated reactions (IARs) were observed in 84.3%, 57.3%, and 57.1% of patients during alemtuzumab courses 1–3, respectively. Serious adverse events (SAEs) were observed in 32.2% of patients, serious IARs in 12.4% of patients, and SAEs other than IARs in 23.1% of patients. Autoimmune adverse events were observed in 30.6% of patients. One patient died of hemophagocytic lymphohistiocytosis, and one patient died of pneumonia. A previously unreported case of thrombotic thrombocytopenic purpura was documented. Conclusions SAEs were more frequent in the present cohort than in previous studies. Even though alemtuzumab is a highly effective therapy for MS, vigorous monitoring with a long enough follow-up time is advised.

scholarly journals Adjuvant Letrozole and Tamoxifen Alone or Sequentially for Postmenopausal Women With Hormone Receptor–Positive Breast Cancer: Long-Term Follow-Up of the BIG 1-98 Trial

2019 ◽  
Vol 37 (2) ◽  
pp. 105-114 ◽  
Author(s):  
Thomas Ruhstaller ◽  
Anita Giobbie-Hurder ◽  
Marco Colleoni ◽  
Maj-Britt Jensen ◽  
Bent Ejlertsen ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Adverse Events ◽  
Contralateral Breast Cancer ◽  
Disease Free Survival ◽  
Luminal Breast Cancer ◽  
Free Survival ◽  
Long Term Follow Up ◽  
Disease Free

Purpose Luminal breast cancer has a long natural history, with recurrences continuing beyond 10 years after diagnosis. We analyzed long-term follow-up (LTFU) of efficacy outcomes and adverse events in the Breast International Group (BIG) 1-98 study reported after a median follow-up of 12.6 years. Patients and Methods BIG 1-98 is a four-arm, phase III, double-blind, randomized trial comparing adjuvant letrozole versus tamoxifen (either treatment received for 5 years) and their sequences (2 years of one treatment plus 3 years of the other) for postmenopausal women with endocrine-responsive early breast cancer. When pharmaceutical company sponsorship ended at 8.4 years of median follow-up, academic partners initiated an observational, LTFU extension collecting annual data on survival, disease status, and adverse events. Information from Denmark was from the Danish Breast Cancer Cooperative Group Registry. Intention-to-treat analyses are reported. Results Of 8,010 enrolled patients, 4,433 were alive and not withdrawn at an LTFU participating center, and 3,833 (86%) had at least one LTFU report. For the monotherapy comparison of letrozole versus tamoxifen, we found a 9% relative reduction in the hazard of a disease-free survival event with letrozole (hazard ratio [HR], 0.91; 95% CI, 0.81 to 1.01). HRs for other efficacy end points were similar to those for disease-free survival. Efficacy of letrozole versus tamoxifen for contralateral breast cancer varied significantly over time (0- to 5-, 5- to 10-, and > 10-year HRs, 0.62, 0.47, and 1.35, respectively; treatment-by-time interaction P = .005), perhaps reflecting a longer carryover effect of tamoxifen. Reporting of specific long-term adverse events seemed more effective with national registry than with case-record reporting of clinical follow-up. Conclusion Efficacy end points continued to show trends favoring letrozole. Letrozole reduced contralateral breast cancer frequency in the first 10 years, but this reversed beyond 10 years. This study illustrates the value of extended follow-up in trials of luminal breast cancer.

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