Mitchell von Itzstein

Mitchell von Itzstein
University of Texas Southwestern Medical Center | UT Southwestern · Division of General Internal Medicine

Doctor of Medicine

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51
Publications
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444
Citations

Publications

Publications (51)
Article
Purpose Patients with Kirsten rat sarcoma viral oncogene (KRAS)–mutant non–small cell lung cancer (NSCLC) have limited therapeutic options. Based on the activity of nuclear export inhibition in preclinical models, we evaluated this strategy in previously treated, advanced KRAS-mutant NSCLC. Patients and Methods The primary outcomes of this multice...
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Introduction Racial and ethnic disparities in the presentation and outcomes of lung cancer are widely known. To evaluate potential factors contributing to these observations, we measured systemic immune parameters in Black and White patients with lung cancer. Methods Patients scheduled to receive cancer immunotherapy were enrolled in a multi-insti...
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Immune checkpoint inhibitors (ICIs) have revolutionized oncology treatment. However, their success is mitigated by the recognition that ICI-induced immune-related adverse events (irAEs) pose considerable challenges to patients and clinicians. These autoimmune toxicities are heterogeneous, unpredictable, and reflect a disease state resulting from a...
Preprint
The interaction between antigens and antibodies (B cell receptors, BCRs) is the key step underlying the function of the humoral immune system in various biological contexts. The capability to profile the landscape of antigen-binding affinity of a vast number of BCRs will provide a powerful tool to reveal novel insights at unprecedented levels and w...
Preprint
Introduction: Racial and ethnic disparities in the presentation and outcomes of lung cancer are widely known. To evaluate potential factors contributing to these observations, we measured systemic immune parameters in Black and White patients with lung cancer. Methods: Patients scheduled to receive cancer immunotherapy were enrolled in a multi-inst...
Article
8597 Background: KRAS mutant NSCLC remains a therapeutic challenge. Although KRAS G12C inhibitors are now approved for cases harboring that specific mutation, their efficacy is modest and the G12C variant accounts for only 40% of KRAS mutations in NSCLC. To date, there are no approved targeted therapies for non-G12C KRAS mutant NSCLC. Selective inh...
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Background Artificial intelligence (AI) chatbots have become a major source of general and medical information, though their accuracy and completeness are still being assessed. Their utility to answer questions surrounding immune-related adverse events (irAEs), common and potentially dangerous toxicities from cancer immunotherapy, are not well defi...
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Immune checkpoint inhibitors (ICI) are increasingly used in combination. To understand the effects of different ICI categories, we characterized changes in circulating autoantibodies in patients enrolled in the E4412 trial (NCT01896999) of brentuximab vedotin (BV) plus ipilimumab, BV plus nivolumab, or BV plus ipilimumab-nivolumab for Hodgkin Lymph...
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Background A useful clinical biomarker requires not only association but also a consistent temporal relationship. For instance, chemotherapy-induced neutropenia and epidermal growth-factor inhibitor-related acneiform rash both occur within weeks of treatment initiation, thereby providing information prior to efficacy assessment. Although immune che...
Article
Telemedicine represents an established mode of patient care delivery that has and will continue to transform cancer clinical research. Through telemedicine, opportunities exist to improve patient care, enhance access to novel therapies, streamline data collection and monitoring, support communication, and increase trial efficiency. Potential challe...
Preprint
Profiling the binding of T cell receptors (TCRs) of T cells to antigenic peptides presented by MHC proteins is one of the most important unsolved problems in modern immunology. Traditional experimental methods to probe TCR-antigen interactions are slow, labor-intensive, costly, and yield moderate throughput. To address this problem, we developed pM...
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Background Immune checkpoint inhibitor (ICI) therapies may cause unpredictable and potentially severe autoimmune toxicities termed immune-related adverse events (irAEs). Because T cells mediate ICI effects, T cell profiling may provide insight into the risk of irAEs. Here we evaluate a novel metric—the T-cell tolerant fraction—as a predictor of fut...
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Introduction: Preclinical studies have demonstrated the ability of radiation therapy (RT) to augment immune response and tumor control by immune checkpoint inhibitors (ICI). However, numerous clinical trials combining RT and ICI have yielded relatively disappointing results. To improve understanding of optimal use of these therapies, we assessed s...
Article
Objectives Immune checkpoint inhibitors (ICIs) cause a variety of toxicities, including immune-related adverse events (irAEs), but there are no biomarkers to predict their development. Guidelines recommend measuring circulating cardiac troponin I (cTnI) during ICI therapy to detect related cardiotoxicities. Moreover, elevated cTnI has also been ass...
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Background Thyroid dysfunction is among the most common autoimmune diseases and immune checkpoint inhibitor (ICI)-induced immune-related adverse events (irAE). We determined the association between longitudinal thyroid function and clinical outcomes in patients treated with ICI. Methods We identified all patients treated with ICI at UT Southwester...
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Introduction Antibiotic exposure is associated with worse clinical outcomes in patients receiving immune checkpoint inhibitors (ICI). We analyzed antibiotic prescription patterns in lung cancer and melanoma, two malignancies in which ICI are used broadly across stages. Methods We performed a retrospective cohort study of adults in the U.S. Veteran...
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Background Pseudoprogression, the initial apparent worsening of cancer prior to eventual improvement, is a documented feature of immune checkpoint inhibitor administration and presents a challenge to clinicians distinguishing true progression from pseudoprogression. This phenomenon does not typically occur with traditional cytotoxic chemotherapy. W...
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Introduction Heritable lung cancer may occur in the context of germline TP53 mutations (Li-Fraumeni syndrome). Limited cases of intra-family tumor genomic characteristics have been reported. Main concerns, important clinical findings, primary diagnoses, interventions, outcomes A 40-year-old woman with no smoking history or known environmental expo...
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Antibiotic administration is associated with worse clinical outcomes and changes to the gut microbiome in cancer patients receiving immune checkpoint inhibitors (ICI). However, the effects of antibiotics on systemic immune function are unknown. We, therefore, evaluated antibiotic exposure, therapeutic responses, and multiplex panels of 40 serum cyt...
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Introduction EGFR L747P mutations occur rarely, with limited preclinical research and case reports suggesting resistance to osimertinib. Main concerns, important clinical findings, primary diagnoses, interventions, outcomes An 84-year-old white male with remote smoking history presented with bilateral pulmonary nodules and multiple subcentimeter e...
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The timing of immune-related adverse events (irAE) associated with immune checkpoint inhibitors (ICI) is highly variable. Although the development of irAE has been associated with ICI clinical benefit, how irAE timing influences this association is unknown. We analyzed two independent cohorts including 154 patients with non-small cell lung cancer (...
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Immune-related adverse events (irAE) may affect almost any organ system and occur at any point during treatment with immune checkpoint inhibitors (ICI). We present a patient with advanced lung cancer receiving antiprogrammed death 1 checkpoint inhibitor who developed a delayed-onset visual irAE treated with corticosteroids. Through assessment of lo...
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Changes in MAPK signaling allow lung cancer cells to transition between lineages that respond differently to treatment.
Article
Importance: As cancer treatment has become more individualized, oncologic clinical trials have become more complex. Increasingly numerous and stringent eligibility criteria frequently include tumor molecular or genomic characteristics that may not be readily identified in medical records, rendering it difficult to best match clinical trials with c...
Article
In this issue, the study by Dagnino and colleagues represents an important addition to the maturing field of blood-based biomarkers for lung cancer screening. Their comprehensive approach to analyzing circulating inflammatory proteins identified CDCP1 as a potential biomarker for distinguishing patients with or without lung cancer, a finding that w...
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Background Increased body mass index (BMI) has been associated with improved response to immune checkpoint inhibitors (ICIs) in multiple cancer types. We evaluated associations between BMI, ICI dosing strategy, and clinical outcomes. Methods We abstracted clinical data on patients with cancer treated with ICI, including age, sex, cancer type, BMI,...
Article
PURPOSE Advances in genomic techniques have led to increased use of next-generation sequencing (NGS). We evaluated the extent to which these tests guide treatment decisions. METHODS We developed and distributed a survey assessing NGS use and outcomes to a survey pool of ASCO members. Comparisons between groups were performed with Wilcoxon two-samp...
Article
Immune checkpoint inhibitor (ICI) therapy is now in widespread clinical use for the treatment of lung cancer. Although patients with autoimmune disease and other comorbidities were excluded from initial clinical trials, emerging real-world experience suggests that these promising treatments may be administered safely to individuals with inactive lo...
Article
Pancreatic cancer is expected to become the second leading cause of cancer-related death within the next few years. Current therapeutic strategies have limited effectiveness and therefore there is an urgency to develop novel effective therapies. The receptor tyrosine kinase subfamily TAM (Tyro3, Axl, MerTK) is directly implicated in the pathogenesi...
Article
3043 Background: Baseline circulating white blood cell differential counts have been proposed as possible markers of response to Immune therapy (ICI) and immune toxicity (irAE), but have not been validated for clinical practice. Methods: 214 patients with various cancers receiving ICI had clinical lab results and overall/organ specific irAE analyze...
Article
e15103 Background: Immune checkpoint inhibitors (ICI) frequently cause thyroid dysfunction. We performed a longitudinal analysis of thyroid function tests in a large, single-center cohort of patients with multiple cancer types receiving ICI. Methods: We performed a retrospective medical records review of consecutive patients treated with ICI from 1...
Article
e15126 Background: The mechanisms by which immune checkpoint inhibitors (ICI) cause immune related adverse events (irAE) are not clear. No current blood tests predict which patients will suffer irAEs. Methods: 70 cancer patients had blood drawn prior to ICI and then 4-6 weeks later. 63 had lung cancer; median age was 69 yrs; 21 were female and medi...
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Immune-related adverse events induced by immune checkpoint inhibitor (ICI) therapy may affect diverse organ systems, including skeletal and cardiac muscle. ICI-associated myositis may result in substantial morbidity and occasional mortality. We present a case of a patient with advanced non-small cell lung cancer who developed grade 4 myositis with...
Article
Background: Immune checkpoint inhibitors (ICIs) have revolutionized the treatment of multiple cancers. However, these promising therapies may also cause immune-related adverse events (irAEs) in a substantial proportion of patients. These autoimmune phenomena may affect almost any organ system and may occur at almost any point in therapy. In some i...
Article
Despite the remarkable success of immune checkpoint inhibitor (ICI) therapy, a significant number of patients develop severe and unpredictable immune-related adverse events (irAEs) affecting a wide variety of organs. Concerns over irAE have led to the exclusion of patients with autoimmune disease from ICI clinical trials. Role of host genetic and i...
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Background Clinical outcomes for resected early‐stage non‐small cell lung cancer (NSCLC) are superior at high‐volume facilities, but reasons for these differences remain unclear. Understanding these differences and optimizing outcomes across institutions are critical to the management of the increasing incidence of these cases. We evaluated the ext...
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Introduction Advances in surgical techniques have improved clinical outcomes and decreased complications. At the same time, heightened attention to care quality has resulted in increased identification of hospital-acquired adverse events. We evaluated these divergent effects on the reported safety of lung cancer resection. Methods and materials We...
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Immune checkpoint inhibitor (ICI)-induced immune-related adverse events (irAEs) may affect almost any organ system and occur at any point during therapy. Autoantibody analysis may provide insight into the mechanism, nature, and timing of these events. We report a case of ICI-induced late-onset Raynaud's-like phenomenon in a patient receiving combin...
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Background Although there is increased attention to designing and explaining clinical trials in ways that are clinically meaningful for patients, there is limited information on patient preferences, understanding, and perceptions of this content. Methods Maximum difference scaling (MaxDiff) methodology was used to develop a survey for assessing pa...
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Introduction The use of molecular biomarkers to guide lung cancer management has led to increasing frequency and amounts of tissue required for repeat lung biopsies. While patient safety and reporting of adverse events has been increasingly emphasized in recent decades, the safety of lung biopsies in patients with lung cancer has only been studied...
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Background With the expansion of non–small cell lung cancer (NSCLC) screening methods, the percentage of cases with early‐stage NSCLC is anticipated to increase. Yet it remains unclear how the type and case volume of the health care facility at which treatment occurs may affect surgery selection and overall survival for cases with early‐stage NSCLC...
Article
Older adults are disproportionately affected by influenza morbidity and mortality. In most high income countries, influenza vaccine policies target persons age ≥65 years for influenza vaccination. Many low-resource settings do not utilize seasonal influenza vaccination. Barriers to influenza prevention among older adults around the globe are multip...
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Skull base osteomyelitis in the setting of granulomatosis with polyangiitis (GPA) is rare and entails significant diagnostic challenges. We present a case of a 65-year-old Caucasian man with a history of rheumatoid arthritis, off immunosuppression for 18 months, who presented with 2 years of chronic headaches, severe fatigue, saddle nose deformity...

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