Exceptional Responders in Oncology: An International Systematic Review and Meta-analysis of Patient Level Data

e24096 Background: Immune checkpoint inhibitors can sometimes lead to fatal outcomes or significant morbidity due to immune-related adverse events (IRAE). Cardiac IRAE, especially myocarditis, are among the most fatal IRAE. There are scarce of the trials addressing the optimal therapeutic approaches for patients with IR-myocarditis. Initial therapy with high-dose steroids (1000 mg of prednisolone for 3-5 days) may be beneficial for many patients with this IRAE and this approach is endorsed by NCCN guidelines. We conducted a systematic review with individual patient-level data meta-analysis of published clinical cases to assess impact of various initial therapeutic modalities and adherence to NCCN guidelines on outcomes of immune-related myocarditis, associated with checkpoint inhibitors. Methods: We searched PubMed database for all full-text articles and abstracts on the treatment of patients with cardiac-related IRAE treated with various PD-1/PD-L1 or CTLA-4 inhibitors for years between 2012 and 2020 in English. The Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) tool was used to ensure transparent reporting. Main study inclusion criteria were: 1) morphologically confirmed immune-related myocarditis or highly clinically suspected autoimmune myocarditis (based on Bonaca et al, 2019 criteria); 2) clear association of IRAE and administration of check-point inhibitors; 3) availability of individual patient and treatment data. Pooled analysis of outcomes and multiple logistic regression analysis were conducted. The primary outcome of this study was rate of major cardiac adverse events (MACE) due to immune-related autoimmune myocarditis according to adherence to NCCN guidelines. MACE was defined as death or persisting significant disabilities due to myocarditis (ie, chronic heart failure, rhythm abnormalities or deterioration leading to impossibility of further anticancer treatment). Results: We identified 277 articles and screened them for title and abstract. After the review process we selected 81 studies for further analysis which described treatment course for 111 patients. Overall, 26 and 85 patients were treated with high-dose and non-high dose steroids. Among patients treated high-dose steroids therapy and non-high dose steroids 10 (38.5%) and 57 (67.1%) of patients respectively experienced MACE (HR 0.185; 95% CI 0.07-0.47; p = 0.0091). Initial treatment failure was associated with high rate of morbidity; however, 9 patients were rescued with various immunosuppressive drugs (eg, tacrolimus, alemtuzumab, tocilizumab). Conclusions: Our results support use of high-dose pulse therapy as a preferred therapeutic approach for all patients with suspected or proven immune-related myocarditis.

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Cerclage for sonographic short cervix in singleton gestations without prior spontaneous preterm birth: systematic review and meta-analysis of randomized controlled trials using individual patient-level data

Ultrasound in Obstetrics and Gynecology ◽

10.1002/uog.17457 ◽

2017 ◽

Vol 50 (5) ◽

pp. 569-577 ◽

Cited By ~ 41

Author(s):

V. Berghella ◽

A. Ciardulli ◽

O. A. Rust ◽

M. To ◽

K. Otsuki ◽

...

Keyword(s):

Systematic Review ◽

Meta Analysis ◽

Controlled Trials ◽

Spontaneous Preterm Birth ◽

Short Cervix ◽

Patient Level Data ◽

Individual Patient Level ◽

Patient Level ◽

Randomized Controlled ◽

Level Data

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Genetic mutations and features of mantle cell lymphoma: a systematic review and meta-analysis

Blood Advances ◽

10.1182/bloodadvances.2019001350 ◽

2020 ◽

Vol 4 (13) ◽

pp. 2927-2938 ◽

Cited By ~ 2

Author(s):

Holly A. Hill ◽

Xinyue Qi ◽

Preetesh Jain ◽

Krystle Nomie ◽

Yucai Wang ◽

...

Keyword(s):

Systematic Review ◽

Mantle Cell Lymphoma ◽

Cell Lymphoma ◽

Meta Analysis ◽

Patient Level Data ◽

Targeted Next Generation Sequencing ◽

Patient Level ◽

Mutational Status ◽

Level Data ◽

Mantle Cell

Abstract Mantle cell lymphoma (MCL) is an incurable rare subtype of non-Hodgkin lymphoma and is subject to relapse and therapeutic resistance. Molecular aberrations in MCL affect pathogenesis, prognosis, and therapeutic response. In this systematic review, we searched 3 databases and selected 32 articles that described mutations in MCL patients. We then conducted a meta-analysis using a Bayesian multiregression model to analyze patient-level data in 2127 MCL patients, including prevalence of mutations. In tumor or bone marrow samples taken at diagnosis or baseline, ATM was the most frequently mutated gene (43.5%) followed by TP53 (26.8%), CDKN2A (23.9%), and CCND1 (20.2%). Aberrations were also detected in IGH (38.4%) and MYC (20.8%), primarily through cytogenetic methods. Other common baseline mutations were NSD2 (15.0%), KMT2A (8.9%), S1PR1 (8.6%), and CARD11 (8.5%). Our data also show a change in mutational status from baseline samples to samples at disease progression and present mutations of interest in MCL that should be considered for future analysis. The genes with the highest mutational frequency difference (>5%) are TP53, ATM, KMT2A, MAP3K14, BTK, TRAF2, CHD2, TLR2, ARID2, RIMS2, NOTCH2, TET2, SPEN, NSD2, CARD11, CCND1, SP140, CDKN2A, and S1PR1. These findings provide a summary of the mutational landscape of MCL. The genes with the highest change in mutation frequency should be included in targeted next-generation sequencing panels for future studies. These findings also highlight the need for analysis of serial samples in MCL. Patient-level data of prevalent mutations in MCL provide additional evidence emphasizing molecular variability in advancing precision medicine initiatives in MCL.

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Faculty Opinions recommendation of Survival benefit of primary prevention implantable cardioverter-defibrillator therapy after myocardial infarction: does time to implant matter? A meta-analysis using patient-level data from 4 clinical trials.

Faculty Opinions – Post-Publication Peer Review of the Biomedical Literature ◽

10.3410/f.717980033.793479806 ◽

2013 ◽

Author(s):

Robert Sheldon ◽

Tarek Hatoum

Keyword(s):

Myocardial Infarction ◽

Clinical Trials ◽

Primary Prevention ◽

Survival Benefit ◽

Meta Analysis ◽

Implantable Cardioverter Defibrillator Therapy ◽

Patient Level Data ◽

Cardioverter Defibrillator ◽

Patient Level ◽

Level Data

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Penumbral imaging and functional outcome in patients with anterior circulation ischaemic stroke treated with endovascular thrombectomy versus medical therapy: a meta-analysis of individual patient-level data

The Lancet Neurology ◽

10.1016/s1474-4422(18)30314-4 ◽

2019 ◽

Vol 18 (1) ◽

pp. 46-55 ◽

Cited By ~ 81

Author(s):

Bruce C V Campbell ◽

Charles B L M Majoie ◽

Gregory W Albers ◽

Bijoy K Menon ◽

Nawaf Yassi ◽

...

Keyword(s):

Ischaemic Stroke ◽

Functional Outcome ◽

Medical Therapy ◽

Meta Analysis ◽

Anterior Circulation ◽

Endovascular Thrombectomy ◽

Patient Level Data ◽

Individual Patient Level ◽

Patient Level ◽

Level Data

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Cutaneous Manifestations of COVID-19: A Systematic Review and Analysis of Individual Patient-Level Data

SSRN Electronic Journal ◽

10.2139/ssrn.3677917 ◽

2020 ◽

Author(s):

David S. Lee ◽

Paradi Mirmirani ◽

Patrick McCleskey ◽

Majid Mehrpouya ◽

Farzam Gorouhi

Keyword(s):

Systematic Review ◽

Cutaneous Manifestations ◽

Patient Level Data ◽

Individual Patient Level ◽

Patient Level ◽

Level Data

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Abstract 17059: Re-Use of Clinical Trial Data From the NHLBI Data Repository (BioLINCC) for Patient-Level Meta-Analyses of Cardiovascular Outcomes: Challenges and Opportunities

Circulation ◽

10.1161/circ.138.suppl_1.17059 ◽

2018 ◽

Vol 138 (Suppl_1) ◽

Author(s):

Helena Sviglin ◽

Gauri Dandi ◽

Eileen Navarro Almario ◽

Tejas Patel ◽

Colin O Wu ◽

...

Keyword(s):

Risk Factors ◽

Meta Analysis ◽

Cardiovascular Outcomes ◽

Data Repository ◽

Common Data Elements ◽

Patient Level Data ◽

Patient Level ◽

Level Data ◽

Data Elements ◽

Meta Analyses

Introduction: An objective of the Meta-AnalyTical Interagency Group (MATIG) is to conduct patient-level meta-analyses of cardiovascular outcomes using data from publicly available repositories. We describe challenges with data re-use from a seminal trial, provide a systematic approach to identify and curate data elements for hypothesis generation, and establish stackable trials to support these analyses. Methods: We used data from the ACCORD trial to assess risk factors and their gender specific differences for the event of hospitalization or death due to heart failure (hdHF), in patients with type 2 diabetes*. We identified the data elements needed to answer the research questions, reviewed the trial protocol to verify definitions, extracted patient-level data, performed quality assessment and statistical analysis. The results showed a gender difference in the effect of intensive vs. standard glucose-lowering therapy on hdHF. To validate the findings, we sought additional trials in BioLINCC to develop a compendium for meta-analysis, and repeated these steps for each trial. Results: Challenges for reusing the ACCORD trial included access to complete patient-level data and metadata. The compendium, developed to evaluate the stackability** of data across trials, identified differences in trial designs, patient populations, study interventions, and data elements that may impact the feasibility and interpretation of meta-analysis. An example of compendium components is shown in Table 1. Conclusion: High-quality metadata facilitate re-use of trial repository data. This compendium standardizes common data elements for gender, racial and age-group specific outcome assessment in major clinical trials. It provides the framework to assess the fitness of trials for patient-level meta-analyses. Efforts are underway by MATIG to expand the compendium to include risk factors and major cardiovascular outcomes across multiple large trials for meta-analysis.

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