Reversal of SARS-CoV2 Induced Hypoxia by Nebulized Sodium-Ibuprofen in a Compassionate Use Program

Abstract BackgroundSodium-ibuprofenate in hypertonic saline (NaIHS) administered directly to the lungs by nebulization and inhalation has antibacterial and anti-inflammatory effects with the potential to deliver these benefits to hypoxic patients. We describe a compassionate use program that offered this therapy to hospitalized COVID-19 patients.MethodsNaIHS (50 mg ibuprofen, tid) was provided in addition to standard of care to hospitalized Covid-19 patients until oxygen saturation levels of >94% were achieved on ambient air. Patients wore a containment hood to diminish aerosolization. Outcome data from participating patients treated at multiple hospitals in Argentina between April 04, 2020, through October 31, 2020 are summarized.Results383 patients were treated, including 327 not on mechanical ventilation at baseline (MV) and 56 ICU patients receiving MV. For those not on baseline MV (59±0.8 years), 64% were male, most with at least one recognized risk factor for disease severity, and mean NEWS2 score prior to treatment initiation of 7.0±0.1. The average length of stay (ALOS) was 11.5±0.3 days and length of treatment (LOT) 9.0±0.2 days. In patients on baseline MV (60.6±2.2 years), 69.9% were male, baseline mean NEWS2 Score was 8.8±0.4, ALOS 15.5±1.4 days and LOT 10.5±0.7 days. Reversal of deterioration in oxygenation and NEWS2 scores was observed acutely following initiation of therapy. Overall in-hospital mortality was 10.7% among patients not on MV at baseline, and 19.6% among patients receiving MV at baseline. No serious adverse events were considered related to ibuprofen therapy.ConclusionsTreatment of COVID-19 pneumonitis with inhalational nebulized NaIHS was associated with rapid improvement in hypoxia and vital signs, with no serious adverse events attributed to therapy. Nebulized NaIHS is worthy of further study in randomized, placebo-controlled trials.(ClinicalTrials.gov:NCT04382768).

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A Multicenter Clinical Study of the Safety and Activity of Maleimide-Polyethylene Glycol–modified Hemoglobin (Hemospan®) in Patients Undergoing Major Orthopedic Surgery

Anesthesiology ◽

10.1097/00000542-200612000-00015 ◽

2006 ◽

Vol 105 (6) ◽

pp. 1153-1163 ◽

Cited By ~ 66

Author(s):

Christina Olofsson ◽

Torbjörn Ahl ◽

Torsten Johansson ◽

Sune Larsson ◽

Per Nellgård ◽

...

Keyword(s):

Polyethylene Glycol ◽

Adverse Events ◽

Spinal Anesthesia ◽

Vital Signs ◽

Standard Of Care ◽

Holter Monitoring ◽

Serious Adverse Events ◽

Major Orthopedic Surgery ◽

American Society ◽

American Society Of Anesthesiologists

Background Hemospan (Sangart Inc., San Diego, CA), a polyethylene glycol-modified hemoglobin with unique oxygen transport properties, has successfully completed a phase I trial in healthy volunteers. Because adverse events are expected to increase with age, the authors conducted a phase II safety study of Hemospan in elderly patients undergoing elective hip arthroplasty during spinal anesthesia. Methods Ninety male and female patients, American Society of Anesthesiologists physical status I-III, aged 50-89 yr, in six Swedish academic hospitals were randomly assigned to receive either 250 or 500 ml Hemospan or Ringer's acetate (30 patients/group) before induction of spinal anesthesia. Safety assessment included vital signs and Holter monitoring from infusion to 24 h, evaluation of laboratory values, and fluid balance. The hypothesis to be tested was that the incidence of adverse events would be no more frequent in patients who received Hemospan compared with standard of care (Ringer's acetate). Results Three serious adverse events were noted, none of which was deemed related to study treatment. Liver enzymes, amylase, and lipase increased transiently in patients in all three groups. There were no significant differences in electrocardiogram or Holter parameters, but there was a suggestion of more bradycardic events in the treated groups. Hypotension was less frequent in the treated patients compared with controls. Conclusions In comparison with Ringer's acetate, Hemospan mildly elevates hepatic enzymes and lipase and is associated with less hypotension and more bradycardic events. The absence of a high frequency of serious adverse events suggests that further clinical trials should be undertaken.

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Compassionate Use of REGEN-COV ® in Patients with COVID-19 and Immunodeficiency-Associated Antibody Disorders

Clinical Infectious Diseases ◽

10.1093/cid/ciab1059 ◽

2021 ◽

Author(s):

David Stein ◽

Ernesto Oviedo-Orta ◽

Wendy A Kampman ◽

Jennifer McGinniss ◽

George Betts ◽

...

Keyword(s):

Adverse Events ◽

Retrospective Analysis ◽

Treatment Options ◽

Clinical Status ◽

Outcome Data ◽

Compassionate Use ◽

Rt Pcr ◽

Serious Adverse Events ◽

Oxygenation Status ◽

Related Reaction

Abstract Background Patients with immunodeficiency-associated antibody disorders are at a higher risk of prolonged/persistent COVID-19 infection, having no viable treatment options. Methods A retrospective analysis of patients with primary and/or secondary immunodeficiency-associated antibody disorders who received casirivimab and imdevimab (REGEN-COV ®) under emergency compassionate use. Objectives describe safety and response to REGEN-COV, focusing on the subset of patients who had COVID-19 duration ≥21 days before treatment. Results Quantitative (change in oxygenation status and/or viral load) and/or qualitative (physician-reported clinical status) patient outcomes data are reported from 64 patients who received REGEN-COV. Improvement in ≥1 outcome was observed in 90.6% of the overall patient group. Thirty-seven of these had COVID-19 duration ≥21 days before treatment; median time from diagnosis to REGEN-COV was 60.5 days. Of the 29 patients with COVID-19 duration ≥21 days before treatment and available outcome data, 96.6% showed improvement in ≥1 outcome. In the 14 patients with post-treatment RT-PCR results available, 11 (78.6%) reported a negative RT-PCR following treatment, with 5 (45.5%) reporting a negative RT-PCR within 5 days and 8 (72.7%) within 21 days of treatment. Ten of 85 patients (11.8%) experienced serious adverse events, only one was an infusion-related reaction, possibly related to REGEN-COV. Two deaths were reported, neither were attributed to REGEN-COV. Conclusions In this retrospective analysis of immunodeficient patients granted REGEN-COV under the compassionate use program, REGEN-COV treatment was associated with rapid viral clearance and clinical improvement in patients with long-standing COVID-19. Adverse events were consistent with COVID-19 and its associated complications, and due to patients’ concurrent medical conditions.

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Comparison of Inpatient Standard-of-Care to Outpatient Oritavancin Therapy for Patients With Acute Uncomplicated Cellulitis

Journal of Pharmacy Practice ◽

10.1177/08971900211021258 ◽

2021 ◽

pp. 089719002110212

Author(s):

Brandy Williams ◽

Justin Muklewicz ◽

Taylor D. Steuber ◽

April Williams ◽

Jonathan Edwards

Keyword(s):

Hospital Readmission ◽

Average Length ◽

Hospital Readmissions ◽

Standard Of Care ◽

Economic Outcomes ◽

Day Hospital ◽

Outpatient Parenteral Antimicrobial Therapy ◽

Average Length Of Stay ◽

Observational Cohort ◽

The Difference

Background: Shifting inpatient antibiotic treatment to outpatient parenteral antimicrobial therapy may minimize treatment for acute bacterial skin and skin structure infections, including cellulitis. The purpose of this evaluation was to compare 30-day hospital readmission or admission due to cellulitis and economic outcomes of inpatient standard-of-care (SoC) management of acute uncomplicated cellulitis to outpatient oritavancin therapy. Methods: This retrospective, observational cohort study was conducted at a 941-bed community teaching hospital. Adult patients 18 years and older treated for acute uncomplicated cellulitis between February 2015 to December 2018 were eligible for inclusion. Information was obtained from hospital and billing department records. Patients were assigned to either inpatient SoC or outpatient oritavancin cohorts for comparison. Results: 1,549 patients were included in the study (1,348 in the inpatient SoC cohort and 201 in the outpatient oritavancin cohort). The average length of stay for patients admitted was 3.6 ± 1.5 days. The primary outcome of 30-day hospital readmission or admission due to cellulitis occurred in 49/1348 (3.6%) patients in the inpatient SoC cohort versus 1/201 (0.5%) in the outpatient oritavancin cohort (p = 0.02). The difference between costs and reimbursement was improved in the outpatient oritavancin group (p < 0.001). Conclusion: Outpatient oritavancin for acute uncomplicated cellulitis was associated with reduction in 30-day hospital readmissions or admissions compared to inpatient SoC. Beneficial economic outcomes for the outpatient oritavancin cohort were observed. Additional studies are required to confirm these findings.

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Randomized phase 2 study of FcRn antagonist efgartigimod in generalized myasthenia gravis

Neurology ◽

10.1212/wnl.0000000000007600 ◽

2019 ◽

Vol 92 (23) ◽

pp. e2661-e2673 ◽

Cited By ~ 39

Author(s):

James F. Howard ◽

Vera Bril ◽

Ted M. Burns ◽

Renato Mantegazza ◽

Malgorzata Bilinska ◽

...

Keyword(s):

Adverse Events ◽

Myasthenia Gravis ◽

Vital Signs ◽

Standard Of Care ◽

Placebo Treatment ◽

Phase 2 ◽

Double Blind ◽

Severity Scores ◽

Quality Of Life Scale ◽

Life Scale

ObjectiveTo investigate safety and explore efficacy of efgartigimod (ARGX-113), an anti-neonatal Fc receptor immunoglobulin G1 Fc fragment, in patients with generalized myasthenia gravis (gMG) with a history of anti-acetylcholine receptor (AChR) autoantibodies, who were on stable standard-of-care myasthenia gravis (MG) treatment.MethodsA phase 2, exploratory, randomized, double-blind, placebo-controlled, 15-center study is described. Eligible patients were randomly assigned (1:1) to receive 4 doses over a 3-week period of either 10 mg/kg IV efgartigimod or matched placebo combined with their standard-of-care therapy. Primary endpoints were safety and tolerability. Secondary endpoints included efficacy (change from baseline to week 11 of Myasthenia Gravis Activities of Daily Living, Quantitative Myasthenia Gravis, and Myasthenia Gravis Composite disease severity scores, and of the revised 15-item Myasthenia Gravis Quality of Life scale), pharmacokinetics, pharmacodynamics, and immunogenicity.ResultsOf the 35 screened patients, 24 were enrolled and randomized: 12 received efgartigimod and 12 placebo. Efgartigimod was well-tolerated in all patients, with no serious or severe adverse events reported, no relevant changes in vital signs or ECG findings observed, and no difference in adverse events between efgartigimod and placebo treatment. All patients treated with efgartigimod showed a rapid decrease in total immunoglobulin G (IgG) and anti-AChR autoantibody levels, and assessment using all 4 efficacy scales consistently demonstrated that 75% showed a rapid and long-lasting disease improvement.ConclusionsEfgartigimod was safe and well-tolerated. The correlation between reduction of levels of pathogenic IgG autoantibodies and disease improvement suggests that reducing pathogenic autoantibodies with efgartigimod may offer an innovative approach to treat MG.Classification of evidenceThis study provides Class I evidence that efgartigimod is safe and well-tolerated in patients with gMG.

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Management of pulmonary toxicity associated with immune checkpoint inhibitors

European Respiratory Review ◽

10.1183/16000617.0012-2019 ◽

2019 ◽

Vol 28 (154) ◽

pp. 190012 ◽

Cited By ~ 14

Author(s):

Myriam Delaunay ◽

Grégoire Prévot ◽

Samia Collot ◽

Laurent Guilleminault ◽

Alain Didier ◽

...

Keyword(s):

Adverse Events ◽

Immune Checkpoint ◽

Pulmonary Toxicity ◽

Immune Checkpoint Inhibitors ◽

Cytotoxic T Lymphocyte ◽

Checkpoint Inhibitors ◽

Standard Of Care ◽

Serious Adverse Events ◽

Programmed Cell Death 1 ◽

Life Threatening

Immunotherapy has become a standard of care in oncology, following the recent approvals of cytotoxic T-lymphocyte-associated protein-4 and programmed cell death-1 inhibitors in lung cancer, melanoma, renal cell carcinoma, Hodgkin's lymphoma, bladder, head and neck cancers. Besides their efficacy, these agents also generate specific immune-related adverse events. Due to the increasing prescription of immune-checkpoint inhibitors, the incidence of immune toxicity will continue to rise. The awareness of immune-related adverse events is key to ensuring both diagnosis and management of the possible serious adverse events. Although severe immune-related adverse events remain rare, they can lead to discontinued treatment or to death if they are not forecasted and managed properly. Even if lung toxicity is not the most frequent adverse event, it remains critical as it can be life-threatening. Herein, the main aspects of pulmonary toxicity are reviewed and guidelines are also proposed in order to manage the possible side-effects.

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Trabectedin for recurrent WHO grade II or III meningioma: A randomized phase II study of the EORTC Brain Tumor Group (EORTC-1320-BTG).

Journal of Clinical Oncology ◽

10.1200/jco.2019.37.15_suppl.2007 ◽

2019 ◽

Vol 37 (15_suppl) ◽

pp. 2007-2007 ◽

Cited By ~ 5

Author(s):

Matthias Preusser ◽

Antonio Silvani ◽

Emilie Le Rhun ◽

Riccardo Soffietti ◽

Giuseppe Lombardi ◽

...

Keyword(s):

Adverse Events ◽

Progression Free Survival ◽

Standard Of Care ◽

Somatostatin Analogue ◽

Synthesis Methods ◽

Serious Adverse Events ◽

Who Grade ◽

Sea Squirt ◽

Grade Ii ◽

Grade 3

2007 Background: EORTC-1320-BTG investigated the activity, safety and quality of life of therapy with the tetrahydroisoquinoline alkaloid trabectedin (Yondelis) in patients with recurrent higher-grade meningiomas. Trabectedin was originally derived from the Caribbean sea squirt, Ecteinascidia turbinata, and currently is manufactured by total synthesis. Methods: Adult patients with histological diagnosis of WHO grade II or III meningioma and radiologically documented progression after maximal feasible surgery and radiotherapy were randomly assigned in a 2:1 ratio to receive intravenous trabectedin (1.5 mg/m2every three weeks) or local standard of care (LOC). The primary endpoint was progression-free survival (PFS). Results: Within 22.1 months, we randomized a total of 90 patients (n=29 in LOC arm, n=61 in trabectedin arm) in 35 institutions and nine countries. In the LOC arm, the following treatments were administered: hydroxyurea (n=11), bevacizumab (n=9), none (n=4), chemotherapy (n=3), somatostatin analogue (n=1), combined chemotherapy and somatostatin analogue (n=1). With 71 PFS events, median PFS was 4.17 months in the LOC and 2.43 months in the trabectedin arm (hazard ratio [HR] for progression, 1.42; 80% CI, 1.00-2.03; p=0.204) with a PFS-6 rate of 29.1% (95% CI, 11.9%-48.8%) in the LOC and 21.1% (95% CI, 11.3%-32.9%) in the trabectedin arm. Median OS was 10.61 months in the LOC and 11.37 months in the trabectedin arm (HR for death, 0.98; 95% CI, 0.54-1.76; p=0.94).Grade 3 to 5 adverse events occurred in 44.4% (18.5% related, 4 serious adverse events, 0 lethal events) of the patients in the LOC and 59% (32.8% related, 57 serious adverse events and 2 toxic deaths) of patient in the trabectedin arm. Conclusions: In this first prospective randomized trial performed in recurrent grade II or III meningioma, trabectedin did not improve PFS and OS and was associated with significantly higher toxicity as compared to LOC treatment. The data collected in this study may serve as benchmark for future clinical trials in this setting. Clinical trial information: NCT02234050.

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Trans Sodium Crocetinate (TSC) to Improve Oxygenation in COVID-19

10.1101/2021.10.08.21264719 ◽

2021 ◽

Author(s):

Adrian Streinu-Cercel ◽

Oana Sandulescu ◽

Victor Daniel Miron ◽

Alina-Alexandra Oana ◽

Maria Magdalena Motoi ◽

...

Keyword(s):

Adverse Events ◽

Dose Level ◽

Study Drug ◽

Standard Of Care ◽

Compartment Model ◽

Supplemental Oxygen ◽

Hospital Length Of Stay ◽

Ordinal Scale ◽

Serious Adverse Events ◽

Efficacy Parameters

Background: Trans Sodium Crocetinate (TSC) is a bipolar synthetic carotenoid under development as a drug to enhance oxygenation to hypoxic tissue in addition to standard of care. TSC acts via a novel mechanism of action, improving the diffusivity of oxygen in blood plasma. Thus, it is based on physical-chemical principles, unlike most drugs which are based on biochemistry-based mechanisms. We explored the use of escalating doses and multiple daily dosing of TSC as a potential therapeutic for patients suffering from hypoxemia due to SARS-CoV-2 infection. Methods: Individuals ≥18 years who were hospitalized with confirmed SARS-CoV-2 infection and hypoxemia, defined as SpO2 < 94% on room air or requiring supplemental oxygen, WHO ordinal scale 3 through 7 (exclusive of Extra Corporeal Membrane Oxygenation [ECMO]) were enrolled in cohorts of six subjects, each of whom received the same dose (0.25, 0.5, 1.0, or 1.5 mg/kg) of TSC via intravenous bolus every 6 hours in addition to standard of care (SOC). This report describes the safety and efficacy results from the lead-in phase of the study and the population pharmacokinetics (PK) analyses. Safety was assessed as the number of serious adverse events and dose-limiting toxicities (DLTs) observed with each dose. Several efficacy parameters were examined in the lead-in phase and descriptive statistics of efficacy parameters are provided. No formal statistical analyses were performed. The population PK analyses were based on previous analyses and examination of the concentration profiles, and two-compartment linear pharmacokinetic models were evaluated and validated. Covariates, including body size, age, sex, organ function, and dose level, were evaluated for inclusion into the model. Results: TSC was well tolerated. There were no treatment emergent adverse events (TEAEs) reported. There were 2 serious adverse events (SAEs) reported during the study, neither were considered treatment-related. A total of 24 (96%) subjects survived. One subject (4.0%) died during the study as a result of an SAE (respiratory failure), and that event was determined to be due to COVID-19 complications and not related to study drug. There was an observed reduction in the time to improvement in WHO Ordinal Scale with increasing dose. The median time to 1-point reduction in subjects receiving 0.25 mg/kg was 11.5 days versus 7.5 days in the 1.5 mg/kg treatment cohort. The overall range across all doses was 1 day to 28 days. A total of 36.0% of subjects had a 1-point improvement in WHO Ordinal Scale to Day 7. The 1.5 mg/kg dose resulted in observed superior outcomes for multiple secondary clinical outcomes: time to 1-point WHO Ordinal Score improvement through Day 29/discharge, 1-point improvement by Day 7, days to return to room air, and hospital length of stay. The PK results showed that the two-compartment model fit the data well. Clearance decreased with increasing dose level and there was no evidence that clearance was affected by covariates other than dose level. Conclusions: These findings suggest that TSC administration every 6 hours at doses up to 1.5 mg/kg for up to 15 days is safe and well tolerated with predictable pharmacokinetics and demonstrated an observed clinical benefit in the treatment of COVID-19-related hypoxemia.

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Efficacy and harms of convalescent plasma for treatment of hospitalized COVID-19 patients: a systematic review and meta-analysis

Archives of Medical Science ◽

10.5114/aoms/132492 ◽

2021 ◽

Author(s):

Alejandro Piscoya ◽

Luis Ng-Sueng ◽

Angela Parra del Riego ◽

Renato Cerna-Viacava ◽

Vinay Pasupuleti ◽

...

Keyword(s):

Adverse Events ◽

Clinical Improvement ◽

Meta Analysis ◽

Random Effect ◽

Standard Of Care ◽

Serious Adverse Events ◽

Quality Of Evidence ◽

All Cause Mortality ◽

Grade Methodology

IntroductionWe systematically reviewed benefits and harms of convalescent plasma (CP) in hospitalized COVID-19 patients.Material and methodsRandomized controlled trials (RCTs) and observational studies assessing CP effects on hospitalized, adult COVID-19 patients were searched until November 24, 2020. We assessed risk of bias (RoB) using Cochrane RoB 2.0 and ROBINS-I tools. Inverse variance random effect meta-analyses were performed. Quality of evidence was evaluated using GRADE methodology. Primary outcomes were all-cause mortality, clinical improvement, and adverse events.ResultsFive RCTs (n = 1067) and 6 cohorts (n = 881) were included. Three and 1 RCTs had some concerns and high RoB, respectively; and there was serious RoB in all cohorts. Convalescent plasma did not reduce all-cause mortality in RCTs of severe (RR = 0.60, 95% CI: 0.33–1.10) or moderate (RR = 0.60, 95% CI: 0.09–3.86) COVID-19 vs. standard of care (SOC); CP reduced all-cause mortality vs. SOC in cohorts (RR = 0.66, 95% CI: 0.49–0.91). Convalescent plasma did not reduce invasive ventilation vs. SOC in moderate disease (RR = 0.85, 95% CI: 0.47–1.55). In comparison to placebo + SOC, CP did not affect all-cause mortality (RR = 0.75, 95% CI: 0.48–1.16) or clinical improvement (HR = 1.07, 95% CI: 0.82–1.40) in severe patients. Adverse and serious adverse events were scarce, similar between CP and controls. Quality of evidence was low or very low for most outcomes.ConclusionsIn comparison to SOC or placebo + SOC, CP did not reduce all-cause mortality in RCTs of hospitalized COVID-19 patients. Convalescent plasma did not have an effect on other clinical or safety outcomes. Until now there is no good quality evidence to recommend CP for hospitalized COVID-19 patients.

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PL3.2 Trabectedin for recurrent WHO grade II or III meningioma: a randomized phase II study of the EORTC Brain Tumor Group (EORTC-1320-BTG)

Neuro-Oncology ◽

10.1093/neuonc/noz126.005 ◽

2019 ◽

Vol 21 (Supplement_3) ◽

pp. iii2-iii3 ◽

Cited By ~ 1

Author(s):

M Preusser ◽

A Silvani ◽

E Le Rhun ◽

R Soffietti ◽

G Lombardi ◽

...

Keyword(s):

Adverse Events ◽

Progression Free Survival ◽

Standard Of Care ◽

Somatostatin Analogue ◽

Serious Adverse Events ◽

Who Grade ◽

Sea Squirt ◽

Tumor Group ◽

Grade Ii ◽

Grade 3

Abstract BACKGROUND EORTC-1320-BTG investigated the activity, safety and quality of life of therapy with the tetrahydroisoquinoline alkaloid trabectedin (Yondelis®) in patients with recurrent higher-grade meningiomas. Trabectedin was originally derived from the Caribbean sea squirt, Ecteinascidia turbinata, and currently is manufactured by total synthesis. METHODS Adult patients with histological diagnosis of WHO grade II or III meningioma and radiologically documented progression after maximal feasible surgery and radiotherapy were randomly assigned in a 2:1 ratio to receive intravenous trabectedin (1.5 mg/m2every three weeks) or local standard of care (LOC). The primary endpoint was progression-free survival (PFS). RESULTS Within 22.1 months, we randomized a total of 90 patients (n=29 in LOC arm, n=61 in trabectedin arm) in 35 institutions and nine countries. In the LOC arm, the following treatments were administered: hydroxyurea (n=11), bevacizumab (n=9), none (n=4), chemotherapy (n=3), somatostatin analogue (n=1), combined chemotherapy and somatostatin analogue (n=1). With 71 PFS events, median PFS was 4.17 months in the LOC and 2.43 months in the trabectedin arm (hazard ratio [HR] for progression, 1.42; 80% CI, 1.00–2.03; p=0.204) with a PFS-6 rate of 29.1% (95% CI, 11.9%-48.8%) in the LOC and 21.1% (95% CI, 11.3%-32.9%) in the trabectedin arm. Median OS was 10.61 months in the LOC and 11.37 months in the trabectedin arm (HR for death, 0.98; 95% CI, 0.54–1.76; p=0.94).Grade 3 to 5 adverse events occurred in 44.4% (18.5% related, 4 serious adverse events, 0 lethal events) of the patients in the LOC and 59% (32.8% related, 57 serious adverse events and 2 toxic deaths) of patient in the trabectedin arm. CONCLUSIONS In this first prospective randomized trial performed in recurrent grade II or III meningioma, trabectedin did not improve PFS and OS and was associated with significantly higher toxicity as compared to LOC treatment. The data collected in this study may serve as benchmark for future clinical trials in this setting.

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Management Of Immunotherapy Adverse Events In Oncological Patients: Anti-Ctla-4, Anti-Pd-1/Pd-L1

Reviews on Recent Clinical Trials ◽

10.2174/1574887115666200622161418 ◽

2020 ◽

Vol 15 ◽

Author(s):

Mattia Brigida ◽

Alessia Perricelli ◽

Fausto Sposato ◽

Maria Giovanna Spadafora ◽

Angelo Pomillo ◽

...

Keyword(s):

Adverse Events ◽

Checkpoint Inhibitors ◽

Standard Of Care ◽

Corticosteroid Treatment ◽

High Dose ◽

Emergency Setting ◽

Serious Adverse Events ◽

Oncological Patients ◽

Grade Ii ◽

Dose Corticosteroid

Background: The widespread use of immunotherapy drugs in the oncological field has led to the spread of new toxicities compared to the more common chemotherapy treatments. This is because immunotherapy with anti-CTLA-4 (Cytotoxic T Lymphocytes-Associated Antigen 4), anti-PD-1 and anti-PD-L1 monoclonal antibodies has become the standard-of-care in a growing number of indications. Any organ or tissue can be involved, but more commonly side effects are reported regarding skin, colon, endocrine glands, liver, lung and kidney. Other less frequent, but more serious, adverse events are neurological and myocarditis. Methods: We performed an electronic search on PUBMED of the literature concerning immunotherapy-related toxicities and their management in oncological patients from 2007 to 2020, with particular attention to the most recent publications. Aim: To summarize the different types of immunotherapy-related toxicities, together with their incidence and diagnosis, and to simplify their management, especially in the emergency setting. Conclusion: Usually, for grade I toxicities it is not recommended to stop immunotherapy; for most of grade II toxicities, immunotherapy should be postponed to when toxicity will have regressed to grade I, considering the possibility of a corticosteroid treatment for most of toxicities. The majority of grade III and IV require administration of high-dose corticosteroid intravenous therapy and suspension of immunotherapy. Mortality related to immune checkpoint inhibitors’ toxicity, occurring at a rate of 0.3-1.3%, is well below fatality rates due to other oncologic interventions and should not discourage the promising results so far reached by immunotherapy.

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