Cutaneous adverse events: a predictor of tumour response under anti‐ PD ‐1 therapy for metastatic melanoma, a cohort analysis of 189 patients

2020 ◽  
Vol 34 (9) ◽  
pp. 2096-2105 ◽  
Author(s):  
L. Bottlaender ◽  
M. Amini‐Adle ◽  
D. Maucort‐Boulch ◽  
P. Robinson ◽  
L. Thomas ◽  
...  
Keyword(s):  
Adverse Events ◽  
Metastatic Melanoma ◽  
Cohort Analysis ◽  
Tumour Response

scholarly journals The Association of Intraoperative driving pressure with postoperative pulmonary complications in open versus closed abdominal surgery patients – a posthoc propensity score–weighted cohort analysis of the LAS VEGAS study

2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Guido Mazzinari ◽  
◽  
Ary Serpa Neto ◽  
Sabrine N. T. Hemmes ◽  
Goran Hedenstierna ◽  
...  
Keyword(s):  
Propensity Score ◽  
Adverse Events ◽  
Abdominal Surgery ◽  
Las Vegas ◽  
Cohort Analysis ◽  
Risk Difference ◽  
Pulmonary Complications ◽  
Driving Pressure ◽  
Postoperative Pulmonary Complications ◽  
Open Abdominal Surgery

Abstract Background It is uncertain whether the association of the intraoperative driving pressure (ΔP) with postoperative pulmonary complications (PPCs) depends on the surgical approach during abdominal surgery. Our primary objective was to determine and compare the association of time–weighted average ΔP (ΔPTW) with PPCs. We also tested the association of ΔPTW with intraoperative adverse events. Methods Posthoc retrospective propensity score–weighted cohort analysis of patients undergoing open or closed abdominal surgery in the ‘Local ASsessment of Ventilatory management during General Anaesthesia for Surgery’ (LAS VEGAS) study, that included patients in 146 hospitals across 29 countries. The primary endpoint was a composite of PPCs. The secondary endpoint was a composite of intraoperative adverse events. Results The analysis included 1128 and 906 patients undergoing open or closed abdominal surgery, respectively. The PPC rate was 5%. ΔP was lower in open abdominal surgery patients, but ΔPTW was not different between groups. The association of ΔPTW with PPCs was significant in both groups and had a higher risk ratio in closed compared to open abdominal surgery patients (1.11 [95%CI 1.10 to 1.20], P <  0.001 versus 1.05 [95%CI 1.05 to 1.05], P <  0.001; risk difference 0.05 [95%CI 0.04 to 0.06], P <  0.001). The association of ΔPTW with intraoperative adverse events was also significant in both groups but had higher odds ratio in closed compared to open abdominal surgery patients (1.13 [95%CI 1.12– to 1.14], P <  0.001 versus 1.07 [95%CI 1.05 to 1.10], P <  0.001; risk difference 0.05 [95%CI 0.030.07], P <  0.001). Conclusions ΔP is associated with PPC and intraoperative adverse events in abdominal surgery, both in open and closed abdominal surgery. Trial registration LAS VEGAS was registered at clinicaltrials.gov (trial identifier NCT01601223).

scholarly journals Ampicillin-Ceftriaxone vs Ampicillin-Gentamicin for Definitive Therapy of Enterococcus faecalis Infective Endocarditis: A Propensity Score–Matched, Retrospective Cohort Analysis

2021 ◽  
Vol 8 (4) ◽  
Author(s):  
Niyati H Shah ◽  
Kathleen A Shutt ◽  
Yohei Doi
Keyword(s):  
Infective Endocarditis ◽  
Propensity Score ◽  
Adverse Events ◽  
Cohort Analysis ◽  
Hospital Readmissions ◽  
Length Of Hospital Stay ◽  
The United States ◽  
Aminoglycoside Resistance ◽  
Definitive Therapy ◽  
Significant Difference

Abstract Background Ampicillin-ceftriaxone (AC) has emerged as an alternative antibiotic regimen for enterococcal infective endocarditis (EIE) with reduced toxicity compared with ampicillin-gentamicin (AG), but evidence regarding its success in reducing EIE-associated death in the United States is limited. Methods We conducted a retrospective, propensity score–matched cohort analysis of EIE patients treated with AC or AG between 2010 and 2017 at 3 hospitals in Pittsburgh, Pennsylvania. We assessed all-cause 90-day mortality as the primary outcome and in-hospital mortality, length of hospital stay, hospital readmissions, adverse events, and relapse of bacteremia as the secondary outcomes. Results A total of 190 patients with EIE (100 treated with AC and 90 with AG) were included. Ninety-day mortality was significantly higher with AC than AG (21% vs 8%; P = .02). After propensity score matching, 56 patients in each group remained for the outcomes analysis. Documented aminoglycoside resistance, presence of annular or aortic abscess, and complete pacemaker removal were the significantly different variables between the 2 matched cohorts. We observed no statistically significant difference in 90-day mortality between the 2 treatment groups (11% vs 7%; P = .55). Adverse events were more common in patients treated with AG (25 vs 39; P = .0091), and more patients in the propensity score–matched AG cohort switched antibiotic regimens than in the AC group (10% vs 49%; P &lt; .0001). Conclusions Patients treated with AC demonstrate no significant differences in mortality, treatment failure, or bacteremia relapse compared with AG in a propensity score–matched EIE cohort.

scholarly journals Comparison of Efficacy in Patients with Metastatic Melanoma Treated with Ipilimumab and Nivolumab Who Did or Did Not Discontinue Treatment Due to Immune-Related Adverse Events: A Real-World Data Study

Cancers ◽  
2021 ◽  
Vol 13 (21) ◽  
pp. 5550
Author(s):  
Morten Fink ◽  
Anders Schwartz Vittrup ◽  
Lars Bastholt ◽  
Inge Marie Svane ◽  
Marco Donia ◽  
...  
Keyword(s):  
Adverse Events ◽  
Metastatic Melanoma ◽  
Real World ◽  
Negative Impact ◽  
Cox Proportional Hazards Model ◽  
Induction Phase ◽  
Discontinue Treatment ◽  
Real World Data ◽  
World Data ◽  
Significant Difference

Immune-related adverse events (irAEs) are very prevalent when treating patients with ipilimumab and nivolumab in combination, and 30–40% of patients discontinue the treatment for this reason. It is of high clinical relevance to investigate the consequences of discontinuing the treatment early since combination therapy with ipilimumab and nivolumab is the first line of treatment for many patients with metastatic melanoma. In this follow-up study, with real-world data from the nationwide DAMMED database, we investigated whether there was a difference in progression-free survival (PFS) and overall survival (OS) for patients who discontinued or did not discontinue treatment within the first four doses of treatment due to irAEs. In total, 448 patients were treated with ipilimumab and nivolumab. Of these, 133 patients discontinued due to irAEs in the induction phase. Using the Cox proportional hazards model, there was no significant difference in PFS when comparing the group that discontinued with the group that did not discontinue. The group that discontinued had a significantly longer OS than the group that received the full length of treatment. Therefore, we conclude that there is no significant negative impact on efficacy for patients who discontinue due to irAEs in the induction phase of combination immunotherapy for metastatic melanoma.

scholarly journals Checkpoint-blocker induced autoimmunity is associated with pretreatment T cell expression profiles and favourable outcome in melanoma

2020 ◽  
Author(s):  
W. Ye ◽  
A Olsson-Brown ◽  
R. A. Watson ◽  
V. T. F. Cheung ◽  
R. D. Morgan ◽  
...  
Keyword(s):  
T Cells ◽  
T Cell ◽  
Clinical Outcome ◽  
Adverse Events ◽  
Metastatic Melanoma ◽  
T Cell Receptor ◽  
Immune Checkpoint ◽  
Single Agent ◽  
Cell Receptor ◽  
Pre Treatment

1Abstract1.1BackgroundImmune checkpoint blockers (ICBs) activate CD8+ T cells to elicit anti-cancer activity but frequently lead to immune-related adverse events (irAEs). The relationship of irAE with baseline parameters and clinical outcome is unclear. We investigated associations between irAE development, CD8+ T cell receptor diversity and expression and clinical outcome in a non-trial setting.1.2MethodsPatients ≥18 years old with metastatic melanoma (MM) receiving combination ICB (ipilimumab plus nivolumab – cICB, n=60) or single-agent ICB (nivolumab/pembrolizumab – sICB, n=78) were prospectively recruited. We retrospectively evaluated the impact of irAEs on survival. This analysis was repeated in an independent cohort of MM patients treated at a separate institution (n=210, cICB:74, sICB:136). We performed RNA sequencing of CD8+ T cells isolated from patients prior to treatment, analysing T cell receptor clonality differential transcript expression according to irAE development.1.3Results48.6% of patients experienced treatment-related irAEs within the first 5 cycles of treatment. Development of irAE prior to the 5th cycle of ICB was associated with longer progression-free and overall survival (PFS, OS) in the primary cohort (log-rank test, PFS: P=0.00034; OS: P<0.0001), replicated in the secondary cohort (OS: P=0.00064). Across cohorts median survival for those patients not experiencing irAE was 14.4 (95% CI:9.6-19.5) months vs not-reached (95% CI:28.9 - Inf), P=3.0×10−7. Pre-treatment performance status and neutrophil count, but not BMI, were additional predictors of clinical outcome. Analysis of CD8+ T cells from 128 patients demonstrated irAE development was associated with increased T cell receptor diversity post-treatment (P=4.3×10−5). Development of irAE in sICB recipients was additionally associated with baseline differential expression of 224 transcripts (FDR<0.1), enriched in pro-inflammatory pathway genes including CYP4F3 and PTGS2.1.4ConclusionsEarly irAE development post-ICB is strongly associated with favourable survival in MM and increased diversity of peripheral CD8+ T cell receptors after treatment. irAE post-sICB is associated with pre-treatment upregulation of inflammatory pathways, indicating irAE development may reflect baseline immune activation states.Key messageImmune-related adverse events (irAEs) commonly occur in patients with metastatic melanoma treated with immune checkpoint blockade (ICB) therapy. In real world setting we find development of early irAEs post-ICB treatment is associated with survival benefit, indicative of a shared mechanism with anti-tumour efficacy. CD8+ T cells from patients who develop irAE show increased receptor diversity, and pre-treatment samples from patients who develop irAE post single-agent anti-PD1 show over-expression of inflammatory pathways, indicating baseline immune state can determine irAE development.

Hair and nail adverse events during treatment with targeted therapies for metastatic melanoma

2016 ◽  
Vol 26 (3) ◽  
pp. 232-239 ◽  
Author(s):  
Emi Dika ◽  
Annalisa Patrizi ◽  
Simone Ribero ◽  
Pier Alessandro Fanti ◽  
Michela Starace ◽  
...  
Keyword(s):  
Adverse Events ◽  
Metastatic Melanoma ◽  
Targeted Therapies

Costs associated with adverse events for systemic therapies in metastatic melanoma

2018 ◽  
Vol 7 (9) ◽  
pp. 867-879 ◽  
Author(s):  
Alex Z Fu ◽  
Zhiyi Li ◽  
Jackson Tang ◽  
Syed Mahmood ◽  
Tyler Whisman ◽  
...  
Keyword(s):  
Adverse Events ◽  
Metastatic Melanoma ◽  
Systemic Therapies

Behcet’s-like syndrome following pembrolizumab: An immune-related adverse event associated with programmed death receptor-1 inhibitor therapy

2019 ◽  
Vol 26 (4) ◽  
pp. 995-999 ◽  
Author(s):  
Steffi Thomas ◽  
Chay Bae ◽  
Tabanor Joy-Ann ◽  
William Traverse
Keyword(s):  
Adverse Events ◽  
Metastatic Melanoma ◽  
Immune Checkpoint ◽  
Immune Checkpoint Inhibitors ◽  
Checkpoint Inhibitors ◽  
Death Receptor ◽  
Programmed Death ◽  
Organ Systems ◽  
Wide Range ◽  
The Right

Introduction The landscape for the treatment of metastatic melanoma has been revolutionized with the introduction immune checkpoint inhibitors. Immune checkpoint inhibitors have now become the standard of care for the treatment of cancers. These immune agents including programmed death receptor-1 inhibitors, programmed death-ligand 1 inhibitors and cytotoxic T-lymphocyte antigen-4 inhibitors have shown promising results but have been associated with numerous immune-related complications. Pembrolizumab, a programmed death receptor-1 inhibitor, has been associated with a number of immune-related adverse events affecting multiple organ systems including integument, ocular, endocrine, cardiovascular, pulmonary, renal, gastrointestinal, and musculoskeletal system. Case report We present a case of an 88-year-old Caucasian male with metastatic melanoma of the face with metastasis to the right fifth cranial nerve and into the right cavernous sinus. He underwent resection of the melanoma and was placed on pembrolizumab at 2 mg/kg every three weeks. Interestingly, 24 months on pembrolizumab therapy, he developed corneal erosions, oral and genital ulcerations. Management and outcome Patient completed his 24 months of pembrolizumab and was started on prednisone and colchicine with improvement in his symptoms. At his follow-up eight months, he had recurrence of an oral ulcer. Discussion Here we present a rare case of an elderly male on pembrolizumab who suffered from corneal erosions, oral and genital ulcers, a syndrome similar to Behcet’s disease. Given that pembrolizumab and other immune checkpoint inhibitors are being utilized in the treatment of cancers, physicians should be aware of the wide range immune-related adverse events including the possible Behcet’s-like syndrome presentation.

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