scholarly journals Adjusted Comparison of Outcomes between Patients from CARTITUDE-1 versus Multiple Myeloma Patients with Prior Exposure to PI, Imid and Anti-CD-38 from a German Registry

Cancers ◽  
2021 ◽  
Vol 13 (23) ◽  
pp. 5996
Author(s):  
Maximilian Merz ◽  
Hartmut Goldschmidt ◽  
Parameswaran Hari ◽  
Mounzer Agha ◽  
Joris Diels ◽  
...  

Ciltacabtagene autoleucel (cilta-cel) is a Chimeric antigen receptor T-cell therapy with the potential for long-term disease control in heavily pre-treated patients with relapsed/refractory multiple myeloma (RRMM). As cilta-cel was assessed in the single-arm CARTITUDE-1 clinical trial, we used an external cohort of patients from the Therapie Monitor registry fulfilling the CARTITUDE-1 inclusion criteria to evaluate the effectiveness of cilta-cel for overall survival (OS) and time to next treatment (TTNT) vs. real-world clinical practice. Individual patient data allowed us to adjust the comparisons between both cohorts, using the inverse probability of treatment weighting (IPW; average treatment effect in the treated population (ATT) and overlap population (ATO) weights) and multivariable Cox proportional hazards regression. Outcomes were compared in intention-to-treat (HR, IPW-ATT: TTNT: 0.13 (95% CI: 0.07, 0.24); OS: 0.14 (95% CI: 0.07, 0.25); IPW-ATO: TTNT: 0.24 (95% CI: 0.12, 0.49); OS: 0.26 (95% CI: 0.13, 0.54)) and modified intention-to-treat (HR, IPW-ATT: TTNT: 0.24 (95% CI: 0.09, 0.67); OS: 0.26 (95% CI: 0.08, 0.84); IPW-ATO: TTNT: 0.26 (95% CI: 0.11, 0.59); OS: 0.31 (95% CI: 0.12, 0.79)) populations. All the comparisons were statistically significant in favor of cilta-cel. These results highlight cilta-cel’s potential as a novel, effective treatment to address unmet needs in patients with RRMM.

2020 ◽  
Author(s):  
Heng Zou ◽  
Wenhao Chen ◽  
Huan Wang ◽  
Li Xiong ◽  
Yu Wen ◽  
...  

Abstract Overview and objective: Although evidence for the application of albumin–bilirubin (ALBI) grading system to assess liver function in hepatocellular carcinoma (HCC) is available, less is known whether it can be applied to determine the prognosis of single HCC with different tumor sizes. This study aimed to address this gap.Methods: Here, we enrolled patients who underwent hepatectomy due to single HCC from the year 2010 to 2014. Analyses were performed to test the potential of ALBI grading system to monitor the long-term survival of single HCC subjects with varying tumor sizes.Results: Overall, 265 participants were recruited. The overall survival (OS) among patients whose tumors were ≤ 7 cm was remarkably higher compared to those whose tumors were > 7 cm. The Cox proportional hazards regression model identified the tumor differentiation grade, ALBI grade, and maximum tumor size as key determinants of the OS. The ALBI grade could stratify the patients who had a single tumor ≤ 7 cm into two distinct groups with different prognoses. The OS between ALBI grades 1 and 2 was comparable for patients who had a single tumor > 7 cm.Conclusions: We show that ALBI grading system can predict disease outcomes of single HCC patients with tumor size ≤ 7 cm. However, the ALBI grade may not predict capability the prognosis of patients with single tumor > 7 cm.


2018 ◽  
Vol 25 (1) ◽  
pp. 107327481879416 ◽  
Author(s):  
Hsiu-Yin Chiang ◽  
Tung-Han Wu ◽  
Chiann-Yi Hsu ◽  
Wen-Cheng Chao

The number of patients with cancer being admitted to intensive care units (ICUs) is increasing worldwide, and these patients are vulnerable to infection. This study aimed to address the long-term impact of positive cultures during admission on 1-year mortality among patients with cancer who received perioperative intensive care. This retrospective cohort study enrolled adult patients with cancer who were admitted to ICUs and received surgery during 2011 to 2016 at a tertiary hospital in central Taiwan. Cancer-related data were retrieved from the cancer registry, and data during ICU admissions were obtained from the electronic medical records. We compared the survival curves between patients with and without positive clinical cultures using log-rank test and used a multivariable Cox proportional hazards regression model to evaluate the influence of positive clinical cultures on 1-year mortality. A total of 638 patients were included for analyses, and 37.9% of them had positive cultures during the index admission. In-hospital mortality was 9.1%, while 1-year mortality was 21.0%. Compared with patients who survived, patients who died were significantly more likely to have positive cultures (59.7% vs 32.1%), to have a higher Acute Physiology and Chronic Health Evaluation II scores (median 21.8 vs 19.0), and to receive mechanical ventilation (86.6% vs 77.4%). Survival analysis found that positive cultures of blood, the respiratory tract, the urinary tract, or the skin and soft tissue were associated with an increased 1-year mortality. Multivariable Cox proportional hazards regression analysis found that positive cultures of blood, the respiratory tract, the urinary tract, or the skin and soft tissue (hazard ratio: 1.621; 95% confidence interval: 1.087-2.419) were significantly associated with 62.1% increased hazards of death within 1 year after the ICU admission. A positive culture during admission was associated with a worsened long-term survival among patients with cancer who received perioperative intensive care. Further studies are needed to confirm this association.


2018 ◽  
Vol 89 (10) ◽  
pp. A21.1-A21
Author(s):  
Katharine Harding ◽  
Elaine Kingwell ◽  
Mark Wardle ◽  
Feng Zhu ◽  
Neil Robertson ◽  
...  

There is evidence that socioeconomic status (SES) is associated with multiple sclerosis (MS) incidence; however it is less clear whether there is also an association with long-term prognosis.3113 patients were selected from the MS registries of British Columbia, Canada (n=2069), and Cardiff, Wales (n=1044). SES, based on neighbourhood-level average income, was measured at onset of MS. Cox proportional hazards regression was used to analyse the association of SES with time to sustained and confirmed EDSS 6.0 and EDSS 4.0. The association between SES and EDSS scores was assessed longitudinally by a linear regression model fitted using generalised estimating equations (GEE) with an exchangeable working correlation structure. All models were adjusted for age at onset, sex, year of onset, initial course and DMT. The cohorts were analysed individually and results combined using meta-analysis.SES was associated with hazard of reaching EDSS 6.0 (adjusted hazard ratio [aHR]=0.90, 95% CI 0.89–0.91), and 4.0 (aHR=0.93, 0.88–0.98). GEE modelling confirmed association of SES with EDSS (β=−0.13, [−0.18- −0.08], p<0.001). We found evidence that lower SES is associated with poorer outcomes. Reasons for this are complex but may include lifestyle or comorbidity. Our findings are relevant for planning and development of MS services.


2020 ◽  
Vol 16 (14) ◽  
pp. 1276-1289
Author(s):  
Han-Wei Zhang ◽  
Victor C. Kok ◽  
Shu-Chun Chuang ◽  
Chun-Hung Tseng ◽  
Chin-Teng Lin ◽  
...  

Background: Alzheimer’s disease, the most common cause of dementia among the elderly, is a progressive and irreversible neurodegenerative disease. Exposure to air pollutants is known to have adverse effects on human health, however, little is known about hydrocarbons in the air that can trigger a dementia event. Objective: We aimed to investigate whether long-term exposure to airborne hydrocarbons increases the risk of developing dementia. Method: The present cohort study included 178,085 people aged 50 years and older in Taiwan. Cox proportional hazards regression analysis was used to fit the multiple pollutant models for two targeted pollutants, including total hydrocarbons and non-methane hydrocarbons, and estimated the risk of dementia. Results: Before controlling for multiple pollutants, hazard ratios with 95% confidence intervals for the overall population were 7.63 (7.28-7.99, p <0.001) at a 0.51-ppm increases in total hydrocarbons, and 2.94 (2.82-3.05, p <0.001) at a 0.32-ppm increases in non-methane hydrocarbons. The highest adjusted hazard ratios for different multiple-pollutant models of each targeted pollutant were statistically significant (p <0.001) for all patients: 11.52 (10.86-12.24) for total hydrocarbons and 9.73 (9.18-10.32) for non-methane hydrocarbons. Conclusion: Our findings suggest that total hydrocarbons and non-methane hydrocarbons may be contributing to dementia development.


2016 ◽  
Vol 34 (2_suppl) ◽  
pp. 615-615
Author(s):  
Liam Connor Macleod ◽  
Scott S. Tykodi ◽  
Sarah Holt ◽  
John L. Gore

615 Background: Many patients with metastatic kidney cancer (mRCC) are ineligible for trials due to non-clear cell histology. Efficacy of targeted therapy agents in non-clear cell mRCC is still being investigated. We hypothesized that sequencing CN upfront is associated with improved overall survival. We analyze a population-based cohort of non-clear cell mRCC patients in the targeted therapy era. Methods: Patients from the SEER-Medicare files (2005-2011) with non-clear cell mRCC were categorized as having received upfront targeted therapy or upfront CN. Additional exclusions were age < 66 to avoid confounding by uncaptured non-Medicare coverage, and competing stage IV cancer. Targeted therapy was identified through Medicare Part D files. Cox proportional hazards regression determined association between treatment groups, clinical and cancer-related characteristics, and the main outcome, median overall survival (OS). Propensity matching controlled for measurable confounding in treatment selection. Results: Of 1,326 mRCC cases, 528 met inclusion criteria of whom 433 (82%) received targeted agents and 172 (33%) underwent CN. Of those not having CN, 74% were diagnosed by biopsy, 10% by cytology, and 16% radiographically (confirmed at autopsy). Thirteen percent received CN then targeted therapy (OS 14 mos, IQR 9-25), 2.5% received targeted therapy then CN (OS 14 mos, IQR 9-26), 18% received CN only (OS 14 mos, IQR5-40), 67% received targeted therapy only (OS 9 mos, IQR 4-19). On multivariable Cox proportional hazards regression upfront CN (regardless of post-CN therapy) was associated with improved OS (HR 0.54,95% CI 0.41,0.72). Using propensity scores, upfront CN patients (N = 161) were matched to upfront targeted therapy patient (N = 111) and the average treatment effect of CN was 8.3 months survival improvement (95% CI 4.0, 13.2). Conclusions: Although utilization of targeted agents in non-clear cell mRCC exceeds 80%, those with greatest OS received CN either upfront or after targeted therapy, though the latter was rare (2.5%). The variety of sequencing strategies observed is evidence of uncertainty regarding the best care for non-clear cell mRCC patients given limited options.


2021 ◽  
Author(s):  
Jingjing Hu ◽  
Ling Gu ◽  
Yueming Shao ◽  
Renfang Zhang ◽  
Tangkai Qi ◽  
...  

Abstract Background Few data are available regarding the long-term case-fatality rate (CFR) among people living with HIV (PLWH) with nontuberculous mycobacteria (NTM) disease. Objectives To analyze the long-term CFR in patients with NTM disease and to identify risk factors for their death. Methods A retrospective cohort study of 379 cases of microbiologically confirmed NTM disease in PLWH was conducted during January 1, 2012 to December 31, 2020 in Shanghai, China. We used Kaplan-Meier survival analysis and log-rank test to compare long-term CFR in patients with disseminated NTM (DNTM) and localized NTM disease. Univariate Cox proportional hazards regression analysis and stepwise Cox proportional hazards regression model were used to estimate the predictors of long-term CFR. Results The cohort was follow-up for a median of 26 months. The total CFR was 15.7% by one year and increased to 22.6% at 5 years after the diagnosis of NTM disease. The 5-year CFR of PLWH with DNTM was significantly higher than that of localized NTM (26.7% vs. 19.6% for DNTM and localized NTM disease, respectively). Older age (hazard ratio [HR] = 1.04, 95% confidence interval [CI]: 1.02-1.06, P < 0.001), comorbidity (HR = 2.05, 95% CI: 1.21-3.49, P < 0.01), DNTM (HR = 2.08, 95% CI: 1.17-3.68, P < 0.05), and HIV viral load (HR = 1.32, 95% CI: 1.12-1.55, P < 0.001) were all independent risk factors of long-term CFR. In the subgroup analysis, time to culture positivity was negatively correlated with CFR in patients with DNTM (HR = 0.90, 95% CI: 0.82-0.98, P < 0.05). Conclusions NTM was associated with significantly high long-term CFR in PLWH. Further approaches to prevent NTM disease in PLWH are urgently needed.


Angiology ◽  
2021 ◽  
pp. 000331972098773
Author(s):  
Ardwan Dakhel ◽  
Gunnar Engström ◽  
Olle Melander ◽  
Stefan Acosta ◽  
Shahab Fatemi ◽  
...  

We evaluated if plasma biomarkers can predict incident peripheral arterial disease (PAD) and mortality in a longitudinal cohort study. Men (n = 3618) and women (n = 1542) were included in the Malmö Preventive Project and underwent analysis of: C-terminal endothelin-1 (CT-proET-1), N-Terminal prosomatostatin (NT-proSST), midregional proatrial natriuretic peptide (MR-proANP), procalcitonin (PCT), and copeptin. Participants were followed up for incident PAD and mortality until December 31, 2016. Median follow-up was 11.2 years (interquartile range 9.4-12.2). Cumulative incidence of PAD was 4.3% (221/5160), 4.5% in men (164/3618) and 3.7% in women (57/1542; P = .174). In an adjusted Cox proportional hazards regression model, higher CT-proET-1 (hazard ratio [HR] 1.8; 95% confidence interval [CI] 1.4-2.3), NT-proSST (HR 1.5; 95% CI 1.2-2.0), and MR-proANP (HR 1.7; 95% CI 1.3-2.3) were independently associated with incident PAD, and higher CT-proET-1 (HR 1.3; 95% CI 1.2-1.5), NT-proSST (HR 1.2; 95% CI 1.1-1.3), MR-proANP (HR 1.4; 95% CI 1.3-1.6), PCT (HR 1.1; 95% CI 1.0-1.2), and copeptin (HR 1.2; 95% CI 1.1-1.4) were independently associated with mortality. Increased levels of CT-proET-1, NT-proSST, and MR-proANP were independently associated with incident PAD, whereas all the vasoactive biomarkers were independently associated with mortality during follow-up.


2020 ◽  
Author(s):  
Danni Wang ◽  
Xin Liang ◽  
Shiyu Xia ◽  
Fei Song ◽  
Huangyao Ru ◽  
...  

Abstract Background The purpose of our study was to explore the relationship between body weight and short- and long-term clinical outcomes in patients with sepsis. Methods We retrospectively analyzed 11,499 patients with sepsis at the Beth Israel Deaconess Medical Center (Boston, MA, USA) registered in the Medical Information Market Intensive Care (MIMIC-III) database from 2001 to 2012. Cox proportional hazards regression assessed the relationships between body mass index and 30-day and 1-year mortality. Results Patients were divided into four groups according to body mass index (underweight: 336 [6.0%]; normal weight: 1,752 [31.4%]; overweight: 1,563 [28.1%]; and obese: 1,920 [34.5%]), 30-day mortality (42.3%, 36.6%, 32.2%, and 29.6%; p<0.001), 1-year mortality, (64.6%, 56.8%, 52.5%, and 46.7%; p<0.001), and in-hospital mortality (35.4%, 34.3%, 31.6%, and 29.9%; p=0.018). In addition, obese patients had notably longer mechanical ventilation periods and intensive care unit and hospital lengths of stay. The Cox proportional hazards regression analysis confirmed that underweight patients had a 13% and 24% increased risk of death within 30 days and 1 year, respectively, compared with normal-weight patients. For overweight patients, these risks were 17% and 14% lower, respectively, than those reported for normal-weight patients. For obese patients, these risks were 22% and 21% lower than those observed in normal-weight patients. Conclusion This retrospective analysis showed that overweight or obese patients showed improved survival within 30 days and 1 year after admission to the intensive care unit.


2020 ◽  
Author(s):  
Wenhao Chen ◽  
Zijian Zhang ◽  
Huan Wang ◽  
Li Xiong ◽  
Yu Wen ◽  
...  

Abstract Background: Although evidence for the application of albumin–bilirubin (ALBI) grading system to assess liver function in hepatocellular carcinoma (HCC) is available, less is known whether it can be applied to determine the prognosis of single HCC with different tumor sizes. This study aimed to address this gap.Methods: Here, we enrolled patients who underwent hepatectomy due to single HCC from the year 2010 to 2014. Analyses were performed to test the potential of ALBI grading system to monitor the long-term survival of single HCC subjects with varying tumor sizes.Results: Overall, 265 participants were recruited. The overall survival (OS) among patients whose tumors were ≤ 7 cm was remarkably higher compared to those whose tumors were > 7 cm. The Cox proportional hazards regression model identified the tumor differentiation grade, ALBI grade, and maximum tumor size as key determinants of the OS. The ALBI grade could stratify the patients who had a single tumor ≤ 7 cm into two distinct groups with different prognoses. The OS between ALBI grades 1 and 2 was comparable for patients who had a single tumor > 7 cm.Conclusions: We show that ALBI grading system can predict disease outcomes of single HCC patients with tumor size ≤ 7 cm. However, the ALBI grade may not predict capability the prognosis of patients with single tumor > 7 cm.


2020 ◽  
Vol 41 (Supplement_2) ◽  
Author(s):  
S Volz ◽  
B Redfors ◽  
C Dworeck ◽  
P Petursson ◽  
M Gotberg ◽  
...  

Abstract Background Intracoronary pressure wire measurements of fractional flow reserve (FFR) and instantaneous wave-free ratio (iFR) provide decision-making guidance during percutaneous coronary intervention (PCI). However, limited data exist on the impact of FFR/iFR on long-term clinical outcomes in patients with stable angina, unstable angina (UA)/non-ST-segment elevation myocardial infarction (NSTEMI), or STEMI. Methods We used data from the Swedish Coronary Angiography and Angioplasty Registry (SCAAR) on all patients in Sweden undergoing PCI (with or without FFR/iFR guidance) for stable angina, UA/NSTEMI, or STEMI between January 2005 and March 2018. The primary endpoint was all-cause mortality and the secondary endpoints were stent thrombosis or restenosis and periprocedural complications. The primary model was multilevel Cox proportional-hazards regression using an instrumental variable (IV) to adjust for known and unknown confounders with treating hospital as a treatment-preference instrument. The following variables were entered into Cox proportional-hazards regression in addition to the IV: age, sex, diabetes, indication for PCI, severity of coronary disease, smoking status, hypertension, hyperlipidemia, previous myocardial infarction, previous PCI, previous coronary artery bypass graft, type of stent. Results In total, 151,001 patients underwent PCI: 31,514 (20.9%) for stable angina, 74,982 (49.6%) for UA/NSTEMI, and 44,505 (29.5%) for STEMI. Of these, FFR/iFR guidance was used in 11,433 patients (7.6%): 5029 (44.0%) with stable angina, 5989 (52.4%) with UA/NSTEMI, and 415 (3.6%) with STEMI; iFR was used in 1156 (10.1%) of these patients. After a median follow-up of 1784 (range 1–4824) days, the FFR/iFR group had lower adjusted risk estimates for all-cause mortality [hazard ratio (HR) 0.79; 95% confidence interval (CI) 0.69–0.91; P=0.001] and stent thrombosis and restenosis (HR 0.13; 95% CI 0.09–0.19; P&lt;0.001). The number of periprocedural complications did not differ significantly between the groups (odds ratio 0.69; 95% CI 0.30–1.55; P=0.368). There was no interaction between FFR/iFR and indication for PCI. We found no difference between FFR and iFR (HR 1.12; 95% CI 0.90–1.59; P=0.216). Conclusions In this observational study, the use of FFR/IFR was associated with a lower risk of long-term mortality in patients undergoing PCI for stable angina, UA/NSTEMI, or STEMI. Our study supports the current European and American guidelines for the use of FFR/iFR during PCI and shows that intracoronary pressure wire guidance has prognostic benefit in patients with stable angina as well as in patients with the acute coronary syndrome. Funding Acknowledgement Type of funding source: Foundation. Main funding source(s): Heart and Lung Foundation, ALF Västra Götaland, Swedish Scientific Council


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