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JCO Oncology Practice Mar 2023Prompt recognition of acute chimeric antigen receptor T (CAR T)-cell-mediated toxicities is crucial because adequate and timely management can prevent or reverse...
Development of a Core Set of Patient- and Caregiver-Reported Signs and Symptoms to Facilitate Early Recognition of Acute Chimeric Antigen Receptor T-Cell Therapy Toxicities.
PURPOSE
Prompt recognition of acute chimeric antigen receptor T (CAR T)-cell-mediated toxicities is crucial because adequate and timely management can prevent or reverse potential life-threatening complications. In the outpatient setting, patients and informal caregivers have to recognize and report signs and symptoms marking these acute toxicities. This study provides a core set of patient- and caregiver-reported signs and symptoms (outcomes, P/CROs) and definitions of red flags warranting immediate action to include in a daily checklist for support at home, with the goal to make outpatient post-CAR T-cell care safer, optimize patient and caregiver support, and thereby facilitating an early discharge/hospital visit reduction strategy.
METHODS
We performed a systematic review of phase II/III trials of US Food and Drug Administration-approved CAR T-cell products and selected all common and severe adverse events that could be translated into a P/CRO for inclusion in a two-round modified Delphi procedure. Eleven CAR T-cell-dedicated hematologists from the Dutch CAR T-cell tumorboard representing all treating centers selected P/CROs for inclusion in the core set and defined red flags. The final core set was evaluated with patients and caregivers.
RESULTS
From nine clinical trials, 457 adverse events were identified of which 42 could be used as P/CRO. The final core set contains 28 items, including five signs for measurement via wearables and two signs for caregiver-performed assessments.
CONCLUSION
This study provides a core set of P/CROs that can serve as a framework for (eHealth) tools that aim to enable patients and caregivers to more effectively recognize and report signs and symptoms of acute toxicities after CAR T-cell therapy, which will enhance safe outpatient treatment monitoring.
Topics: Humans; Immunotherapy, Adoptive; Receptors, Chimeric Antigen; Caregivers; Receptors, Antigen, T-Cell; Outpatients; Cell- and Tissue-Based Therapy
PubMed: 36508702
DOI: 10.1200/OP.22.00501 -
Journal of Global Health Nov 2022Severe acute respiratory infections (SARIs) remain a leading cause of death globally, particularly in low- and middle-income countries (LMICs). Early intervention is...
A systematic review of acute and emergency care interventions for adolescents and adults with severe acute respiratory infections including COVID-19 in low- and middle-income countries.
BACKGROUND
Severe acute respiratory infections (SARIs) remain a leading cause of death globally, particularly in low- and middle-income countries (LMICs). Early intervention is critical, considering the potential for rapid decompensation in patients with SARIs. We aimed to evaluate the impact of acute and emergency care interventions on improving clinical outcomes in patients >10 years old with SARIs in LMICs.
METHODS
A systematic literature search was performed in PubMed, Global Health, and Global Index Medicus databases to identify peer-reviewed studies containing SARI, LMICs, and emergency care interventions. Studies published prior to November 2020 focusing on patients >10 years old were included. A narrative synthesis was performed due to the heterogeneity of identified articles. Risk of bias was assessed using the Risk of Bias 2 and Risk of Bias In Non-Randomized Studies of Interventions tools.
RESULTS
20 223 studies were screened and 58 met the inclusion criteria. Thirty-four studies focused on coronavirus-2019 (COVID-19), 15 on pneumonia, seven on influenza, one study on severe acute respiratory syndrome, and one on undifferentiated SARI. Few COVID-19 studies found a benefit of the tested intervention on clinical status, mortality, or hospital length-of-stay. Little to no benefit was found for azithromycin, convalescent plasma, or zinc, and potential harm was found for hydroxychloroquine/chloroquine. There was mixed evidence for immunomodulators, traditional Chinese medicine, and corticosteroids among COVID-19 studies, with notable confounding due to a lack of consistency of control group treatments. Neuraminidase inhibitor antivirals for influenza had the highest quality of evidence for shortening symptom duration and decreasing disease severity.
CONCLUSIONS
We found few interventions for SARIs in LMICs with have high-quality evidence for improving clinical outcomes. None of the included studies evaluated non-pharmacologic interventions or were conducted in low-income countries. Further studies evaluating the impact of antivirals, immunomodulators, corticosteroids, and non-pharmacologic interventions for SARIs in LMICs are urgently needed.
REGISTRATION
PROSPERO registration number: CRD42020216117.
Topics: Humans; Adolescent; Child; COVID-19; Developing Countries; Influenza, Human; Antiviral Agents; Emergency Medical Services; COVID-19 Serotherapy
PubMed: 36342777
DOI: 10.7189/jogh.12.05039 -
Nature Communications Oct 2022The latest SARS-CoV-2 variant of concern Omicron, with its immune escape from therapeutic anti-Spike monoclonal antibodies and WA-1 vaccine-elicited sera, demonstrates...
The latest SARS-CoV-2 variant of concern Omicron, with its immune escape from therapeutic anti-Spike monoclonal antibodies and WA-1 vaccine-elicited sera, demonstrates the continued relevance of COVID-19 convalescent plasma (CCP) therapies. Lessons learnt from previous usage of CCP suggests focusing on early outpatients and immunocompromised recipients, with high neutralizing antibody titer units. Here, we systematically review Omicron-neutralizing plasma activity data, and report that approximately 47% (424/902) of CCP samples from unvaccinated pre-Omicron donors neutralizes Omicron BA.1 with a very low geometric mean of geometric mean titers for 50% neutralization GM(GMT) of ~13, representing a > 20-fold reduction from WA-1 neutralization. Non-convalescent subjects who had received two doses of mRNA vaccines had a GM(GMT50) for Omicron BA.1 neutralization of ~27. However, plasma from vaccinees recovering from either previous pre-Omicron variants of concern infection, Omicron BA.1 infection, or third-dose uninfected vaccinees was nearly 100% neutralizing against Omicron BA.1, BA.2 and BA.4/5 with GM(GMT()) all over 189, 10 times higher than pre-Omicron CCP. Fully vaccinated and post-BA.1 plasma (Vax-CCP) had a GM(GMT) > 450 for BA.4/5 and >1,500 for BA.1 and BA.2. These findings have implications for both CCP stocks collected in prior pandemic periods and for future plans to restart CCP collections. Thus, Vax-CCP provides an effective tool to combat ongoing variants that escape therapeutic monoclonal antibodies.
Topics: Humans; Neutralization Tests; SARS-CoV-2; Antibodies, Viral; COVID-19; Antibodies, Monoclonal; Antibodies, Neutralizing; Spike Glycoprotein, Coronavirus; COVID-19 Serotherapy
PubMed: 36309490
DOI: 10.1038/s41467-022-33864-y -
Blood Advances Jan 2023Relapsed/refractory primary central nervous system lymphoma (PCNSL) and secondary central nervous system lymphoma (SCNSL) are associated with short survival and... (Meta-Analysis)
Meta-Analysis
Relapsed/refractory primary central nervous system lymphoma (PCNSL) and secondary central nervous system lymphoma (SCNSL) are associated with short survival and represent an unmet need, requiring novel effective strategies. Anti-CD19 chimeric antigen receptor (CAR) T cells, effective in systemic large B-cell lymphoma (LBCL), have shown responses in PCNSL and SCNSL in early reports, but with limited sample size. We, therefore, performed a comprehensive systematic review and meta-analysis of all published data describing CAR T-cell use in PCNSL and SCNSL. This identified 128 patients with PCNSL (30) and SCNSL (98). Our primary objectives were to evaluate CAR T-cell specific toxicity (immune effector cell-associated neurotoxicity syndrome [ICANS] and cytokine release syndrome [CRS]) as well as response rates in these 2 populations. Seventy percent of patients with PCNSL had CRS of any grade (13% grade 3-4) and 53% had ICANS of any grade (18% grade 3-4). Comparatively, 72% of the SCNSL cohort experienced CRS of any grade (11% grade 3-4) and 48% had ICANS of any grade (26% grade 3-4). Of the patients with PCNSL, 56% achieved a complete remission (CR) with 37% remaining in remission at 6 months. Similarly, 47% of patients with SCNSL had a CR, with 37% in remission at 6 months. In a large meta-analysis of central nervous system (CNS) lymphomas, toxicity of anti-CD19-CAR T-cell therapy was similar to that of registrational studies in systemic LBCL with no increased signal of neurotoxicity observed. Encouraging efficacy was demonstrated in patients with CNS lymphoma with no discernible differences between PCNSL and SCNSL.
Topics: Humans; Antigens, CD19; Central Nervous System Neoplasms; Cytokine Release Syndrome; Immunotherapy, Adoptive; Lymphoma, Large B-Cell, Diffuse; Lymphoma, Non-Hodgkin; Neoplasms, Second Primary; Neurotoxicity Syndromes
PubMed: 36260735
DOI: 10.1182/bloodadvances.2022008525 -
Journal of the Indian Society of... 2022Passive immunization using egg yolk-based antibodies has been tested against oral microorganisms. Our study assessed the effect of immunoglobulin Y (IgY) formulations on... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Passive immunization using egg yolk-based antibodies has been tested against oral microorganisms. Our study assessed the effect of immunoglobulin Y (IgY) formulations on Streptococcus mutans, Porphyromonas gingivalis, and Candida albicans in human subjects.
HIGHLIGHTS
VS and UT independently searched articles using keyword combinations in four search engines; studies in English were selected. Either parallel-arm or split-mouth randomized controlled trials on healthy human subjects were considered. Ten studies remained in the selection; six studies compared the effect of IgY formulations on S. mutans, three on P. gingivalis, and one on C. albicans. Five studies (422 subjects) compared the effect of IgY formulations on S. mutans. When fixed-effect model (FEM) was applied, the risk ratio (RR) (confidence interval [CI]) was found to be 7.81 (6.00, 10.18). Three studies (167 subjects) compared the effect of IgY formulations on P. gingivalis. When FEM was applied, the RR (CI) was found to be 0.06 (-0.03, 0.15) in relation to reduction in probing depth. When FEM was applied, for percentage reduction in bleeding on probing (BOP), the RR (CI) was 1.99 (1.64, 2.41). Only one study (26 subjects) was available of IgY formulation and C. albicans; hence meta-analysis was not performed.The search was extended using Google Scholar, Semantic Scholar, cross-references and by contacting authors and researchers in the field which further yielded five articles. .
CONCLUSIONS
IgY formulations were effective in the reduction of S. mutans. They were not effective on P. gingivalis in relation to probing depth but were effective in relation to reduction in BOP. No harms were reported. Evidence is of low quality due to high heterogeneity. The ROB was moderate and publication bias was low.
Topics: Humans; Immunoglobulins; Porphyromonas gingivalis; Streptococcus mutans; Research Subjects; Randomized Controlled Trials as Topic
PubMed: 36260461
DOI: 10.4103/jisppd.jisppd_226_22 -
International Journal of Environmental... Aug 2022This study investigated the efficacy and safety of convalescent plasma (CP) transfusion against the coronavirus disease 2019 (COVID-19) via a systematic review and... (Meta-Analysis)
Meta-Analysis Review
This study investigated the efficacy and safety of convalescent plasma (CP) transfusion against the coronavirus disease 2019 (COVID-19) via a systematic review and meta-analysis of randomized controlled trials (RCTs). A total of 5467 articles obtained from electronic databases were assessed; however, only 34 RCTs were eligible after manually screening and eliminating unnecessary studies. The beneficial effect was addressed by assessing the risk ratio (RR) and standardized mean differences (SMDs) of the meta-analysis. It was demonstrated that CP therapy is not effective in improving clinical outcomes, including reducing mortality with an RR of 0.88 [0.76; 1.03] (I = 68% and = 0.10) and length of hospitalization with SMD of -0.47 [-0.95; 0.00] (I = 99% and = 0.05). Subgroup analysis provided strong evidence that CP transfusion does not significantly reduce all-cause mortality compared to standard of care (SOC) with an RR of 1.01 [0.99; 1.03] (I = 70% and = 0.33). In addition, CP was found to be safe for and well-tolerated by COVID-19 patients as was the SOC in healthcare settings. Overall, the results suggest that CP should not be applied outside of randomized trials because of less benefit in improving clinical outcomes for COVID-19 treatment.
Topics: COVID-19; Humans; Immunization, Passive; Randomized Controlled Trials as Topic; COVID-19 Drug Treatment; COVID-19 Serotherapy
PubMed: 36078338
DOI: 10.3390/ijerph191710622 -
Frontiers in Immunology 2022The objective of this study was to assess whether convalescent plasma therapy could offer survival advantages for patients with novel coronavirus disease 2019... (Meta-Analysis)
Meta-Analysis
UNLABELLED
The objective of this study was to assess whether convalescent plasma therapy could offer survival advantages for patients with novel coronavirus disease 2019 (COVID-19). An electronic search of Pubmed, Web of Science, Embase, Cochrane library and MedRxiv was performed from January 1st, 2020 to April 1st, 2022. We included studies containing patients with COVID-19 and treated with CCP. Data were independently extracted by two reviewers and synthesized with a random-effect analysis model. The primary outcome was 28-d mortality. Secondary outcomes included length of hospital stay, ventilation-free days, 14-d mortality, improvements of symptoms, progression of diseases and requirements of mechanical ventilation. Safety outcomes included the incidence of all adverse events (AEs) and serious adverse events (SAEs). The Cochrane risk-of-bias assessment tool 2.0 was used to assess the potential risk of bias in eligible studies. The heterogeneity of results was assessed by I^2 test and Q statistic test. The possibility of publication bias was assessed by conducting Begg and Egger test. GRADE (Grading of Recommendations Assessment, Development and Evaluation) method were used for quality of evidence. This study had been registered on PROSPERO, CRD42021273608. 32 RCTs comprising 21478 patients with Covid-19 were included. Compared to the control group, COVID-19 patients receiving CCP were not associated with significantly reduced 28-d mortality (CCP 20.0% vs control 20.8%; risk ratio 0.94; 95% CI 0.87-1.02; p = 0.16; I² = 8%). For all secondary outcomes, there were no significant differences between CCP group and control group. The incidence of AEs (26.9% vs 19.4%,; risk ratio 1.14; 95% CI 0.99-01.31; p = 0.06; I² = 38%) and SAEs (16.3% vs 13.5%; risk ratio 1.03; 95% CI 0.87-1.20; p = 0.76; I² = 42%) tended to be higher in the CCP group compared to the control group, while the differences did not reach statistical significance. In all, CCP therapy was not related to significantly improved 28-d mortality or symptoms recovery, and should not be viewed as a routine treatment for COVID-19 patients.
TRIAL REGISTRATION NUMBER
CRD42021273608. Registration on February 28, 2022.
SYSTEMATIC REVIEW REGISTRATION
https://www.crd.york.ac.uk/prospero/, Identifier CRD42022313265.
Topics: COVID-19; Humans; Immunization, Passive; Length of Stay; Respiration, Artificial; COVID-19 Serotherapy
PubMed: 35967398
DOI: 10.3389/fimmu.2022.964398 -
Annals of Geriatric Medicine and... Sep 2022Among all patients infected with coronavirus disease 2019 (COVID-19), the older adult population was the most affected, with 80%-90% of fatalities occurring in this...
BACKGROUND
Among all patients infected with coronavirus disease 2019 (COVID-19), the older adult population was the most affected, with 80%-90% of fatalities occurring in this group. The effectiveness of convalescent plasma (CP) in older adults is considerably more restricted than that in adults, resulting in a demand for data on the efficacy of therapeutic CP in older adults. This meta-analysis of updated literature examined the effect of CP in older adults with COVID-19.
METHODS
Relevant literature was identified from studies indexed in the Cochrane, PubMed, and Google Scholar databases between December 2019 and April 2022. The primary outcome was all-cause mortality. Risk estimates were pooled using a random-effects model. The risk of bias was assessed by regression-based Egger test using the relative risk (RR) and upper and lower confidence intervals (CIs) of the three included studies.
RESULTS
Among 377 studies identified, three full-text studies that included 1,038 patients met the inclusion criteria. The results of our meta-analysis showed that CP administration lowered the mortality risk in older adults with COVID-19 (RR=0.47; 95% CI, 0.26-0.86; p=0.01; I2=0%, p<0.81). CP therapy was more useful if delivered early in the course of the disease (within 72 hours of onset) and in less severe stages of the disease. Mortality tended to be lower in the high-titer group.
CONCLUSIONS
CP treatment was significantly associated with a lower risk of mortality in older adults with COVID-19 than in patients not administered CP. The timing of CP administration is critical since earlier treatment after disease onset was associated with a better prognosis.
PubMed: 35915954
DOI: 10.4235/agmr.22.0045 -
Frontiers in Immunology 2022Different from surgery, chemical therapy, radio-therapy and target therapy, Chimeric antigen receptor-modified T (CAR-T) cells, a novel adoptive immunotherapy strategy,...
Different from surgery, chemical therapy, radio-therapy and target therapy, Chimeric antigen receptor-modified T (CAR-T) cells, a novel adoptive immunotherapy strategy, have been used successfully against both hematological tumors and solid tumors. Although several problems have reduced engineered CAR-T cell therapeutic outcomes in clinical trials for the treatment of thoracic malignancies, including the lack of specific antigens, an immunosuppressive tumor microenvironment, a low level of CAR-T cell infiltration into tumor tissues, off-target toxicity, and other safety issues, CAR-T cell treatment is still full of bright future. In this review, we outline the basic structure and characteristics of CAR-T cells among different period, summarize the common tumor-associated antigens in clinical trials of CAR-T cell therapy for thoracic malignancies, and point out the current challenges and new strategies, aiming to provide new ideas and approaches for preclinical experiments and clinical trials of CAR-T cell therapy for thoracic malignancies.
Topics: Humans; Immunotherapy; Immunotherapy, Adoptive; Receptors, Chimeric Antigen; T-Lymphocytes; Thoracic Neoplasms; Tumor Microenvironment
PubMed: 35911706
DOI: 10.3389/fimmu.2022.871661 -
British Journal of Haematology Sep 2022Treatment with high-dose chemotherapy followed by autologous stem cell transplantation (ASCT) is considered standard of care (SOC) second-line treatment for relapsed or... (Meta-Analysis)
Meta-Analysis
Treatment with high-dose chemotherapy followed by autologous stem cell transplantation (ASCT) is considered standard of care (SOC) second-line treatment for relapsed or refractory large B-cell lymphoma (LBCL). However, outcomes remain suboptimal. A systematic review and meta-analysis of randomised controlled trials comparing efficacy and safety of SOC versus chimeric antigen receptor T-cell (CAR-T) therapy as second-line for patients with LBCL refractory or relapsing within 12 months. Outcomes included overall survival (OS), event-free survival (EFS), overall response rate (ORR) and safety. Three trials published in 2021 (involving 865 participants) fulfilled the eligibility criteria. EFS as well as OS were significantly improved with CAR-T therapy as compared to SOC, hazard ratio (HR) 0.57 (95% confidence interval [CI] 0.49-0.68) and HR 0.77 (95% CI 0.60-0.98) respectively. CAR-T therapy was associated with significantly better ORR, relative risk (RR) 1.55 (95% CI 1.12-2.13, p = 0.001). The risk of Grade III/IV adverse event was comparable between the two arms, RR 1.03 (95% CI 0.93-1.14). In summary, CAR-T therapy has superior outcomes as compared to SOC in patients with LBCL refractory or relapsing within 12 months, without excess of toxicity. Longer follow-up is needed to confirm these results and determine the optimal sequencing of CAR-T therapy in the management of LBCL.
Topics: Antigens, CD19; Hematopoietic Stem Cell Transplantation; Humans; Immunotherapy, Adoptive; Lymphoma, Large B-Cell, Diffuse; Neoplasm Recurrence, Local; Receptors, Antigen, T-Cell; Receptors, Chimeric Antigen; Standard of Care; Transplantation, Autologous
PubMed: 35765220
DOI: 10.1111/bjh.18335