Medical Specialties Commons^™

Combined High-Dose Lattice Radiation Therapy And Immune Checkpoint Blockade For Advanced Bulky Tumors: The Concept And A Case Report, Liuqing Jiang, Xiaobo Li, Jianping Zhang, Wenyao Li, Fangfen Dong, Cheng Chen, Qingliang Lin, Chonglin Zhang, Fen Zheng, Weisi Yan, Yi Zheng, Xiaodong Wu, Benhua Xu

Department of Radiation Oncology Faculty Papers

Although the combination of immune checkpoint blockades with high dose of radiation has indicated the potential of co-stimulatory effects, consistent clinical outcome has been yet to be demonstrated. Bulky tumors present challenges for radiation treatment to achieve high rate of tumor control due to large tumor sizes and normal tissue toxicities. As an alternative, spatially fractionated radiotherapy (SFRT) technique has been applied, in the forms of GRID or LATTICE radiation therapy (LRT), to safely treat bulky tumors. When used alone in a single or a few fractions, GRID or LRT can be best classified as palliative or tumor de-bulking treatments. …

Role Of Immunotherapy In Stage Iv Large Cell Neuroendocrine Carcinoma Of The Lung., Takefumi Komiya Md, Neema Ravindra, Emily Powell Phd

PCI Publications and Projects

BACKGROUND: Despite approvals of immune checkpoint inhibitors in both small cell and non-small cell lung cancers, the role of immunotherapy in large cell neuroendocrine carcinoma (LCNEC) in lung is undefined.

METHODS: Using the National Cancer Database (NCDB), Stage IV lung LCNEC cases diagnosed from 2014 to 2016 were analyzed. Information regarding cancer treatment was limited to first course of therapy, including surgery for primary lesion, radiation, chemotherapy, and immunotherapy. Survival analysis was performed using Kaplan-Meier curves and Log-rank tests. Cox proportional hazard model was used for multivariate analysis.

RESULTS: Among 661 eligible cases, 37 patients were treated with immunotherapy. No …

Targeting Parp-1 With Metronomic Therapy Modulates Mdsc Suppressive Function And Enhances Anti-Pd-1 Immunotherapy In Colon Cancer, Mohamed A. Ghonim, Salome V. Ibba, Abdelmetalab F. Tarhuni, Youssef Errami, Hanh H. Luu, Matthew J. Dean, Ali H. El-Bahrawy, Dorota Wyczechowska, Ilyes A. Benslimane, Luis Del Valle, Amir A. Al-Khami, Augusto C. Ochoa, A Hamid Boulares

School of Graduate Studies Faculty Publications

BACKGROUND: Poly(ADP-ribose) polymerase (PARP) inhibitors (eg, olaparib) are effective against BRCA-mutated cancers at/near maximum tolerated doses by trapping PARP-1 on damaged chromatin, benefitting only small patient proportions. The benefits of targeting non-DNA repair aspects of PARP with metronomic doses remain unexplored. METHODS: Colon epithelial cells or mouse or human bone marrow (BM)-derived-myeloid-derived suppressor cells (MDSCs) were stimulated to assess the effect of partial PARP-1 inhibition on inflammatory gene expression or immune suppression. Mice treated with azoxymethane/four dextran-sulfate-sodium cycles or mice bred into PARP-1 or treated with olaparib were used to examine the role of PARP-1 in colitis-induced or spontaneous colon …

Cross-Reactivity In Skin Prick Test Results Of Members Within Pooideae Subfamily, Brette C. Harding, Brian P. Kinealy, Christine B. Franzese

Otolaryngology--Head & Neck Surgery Resident Research

Objective: Molecular similarities of grass pollen antigens have led to the view that cross-reactivity exists within members of the Pooideae subfamily of grasses. This has resulted in testing for only the most antigenically representative member of Pooideae, Timothy grass (Phleum pratense), despite little literature to support the claim that Phleum is the most representative member or that in vitro cross-reactivity correlates with in vivo cross-reactivity. The aim of the study was to determine if patients with allergic rhinitis symptoms and positive skin prick test results to meadow fescue (Festuca pratensis) also have positive results to Timothy …

Cytopenias After Cd19 Chimeric Antigen Receptor T-Cells (Car-T) Therapy For Diffuse Large B-Cell Lymphomas Or Transformed Follicular Lymphoma: A Single Institution Experience., Andrew Schaefer, Ying Huang, Adam Kittai, Joseph E Maakaron, Caner Saygin, Jonathan Brammer, Sam Penza, Ayman Saad, Samantha M Jaglowski, Basem M William

Oncology Articles

INTRODUCTION: Patients with relapsed/refractory diffuse large B-cell lymphoma (DLBCL) have poor outcomes. Treatment with CD19 chimeric antigen receptor (CAR-T) cells, tisagenlecleucel and axicabtagene ciloleucel, has been associated with improved outcomes. Cytopenias were observed in clinical trials with both products; however, little is known regarding the patterns and outcomes of these cytopenias.

SUBJECTS AND METHODS: We reviewed DLBCL patients (

RESULTS: Median duration of leukopenia, neutropenia, lymphopenia, anemia, and thrombocytopenia was 49, 9, 117.5, 125, and 95.5 days after CAR-T infusion, respectively. Filgrastim was used in 63% of patients, and 50% of patients received red cell or platelet transfusions. With the …

Tisagenlecleucel Infusion In Patients With Relapsed/Refractory All And Concurrent Serious Infection., Erin Hall, Dwight E. Yin, Rakesh K. Goyal, Atif Ahmed, Grace S. Mitchell, Shawn D. St Peter, Terrie Flatt, Ibrahim A. Ahmed, Weijie Li, Richard J. Hendrickson, Keith August, Douglas Myers

Manuscripts, Articles, Book Chapters and Other Papers

BACKGROUND: Tisagenlecleucel, an anti-CD19 chimeric antigen receptor T (CAR-T) cell therapy, has demonstrated durable efficacy and a manageable safety profile in pediatric and young adult patients with relapsed/refractory B-cell acute lymphoblastic leukemia (B-ALL) in the ELIANA pivotal trial and real-world experience. Experience from investigator-led studies prior to ELIANA suggests that infections and inflammatory conditions may exacerbate the severity of cytokine release syndrome (CRS) associated with CAR-T cell therapy, leading to extreme caution and strong restrictions for on-study and commercial infusion of tisagenlecleucel in patients with active infection. CRS intervention with interleukin (IL)-6 blockade and/or steroid therapy was introduced late in …

Pd1 Inhibitor Induced Inverse Lichenoid Eruption: A Case Series, Mansha Sethi, Vaibhav Garg, Jason Lee, Sherry Yang

Department of Dermatology and Cutaneous Biology Faculty Papers

The increased use of monoclonal antibodies that target the immune checkpoint T cell receptor programmed death-1 (PD1) to treat numerous solid tumors has led to several reports describing associated cutaneous adverse events. Although lichenoid reactions have been well described, we propose that PD1 inhibitor-induced inverse lichenoid eruption (PILE) is a distinct variant. We describe two patients who presented with nearly identical deeply erythematous, malodorous, eroded anogenital plaques with focal crusting. Diagnosis of PILE was established given the biopsy findings and temporal association with PD1 inhibitor therapy. Treatment with clobetasol ointment was successful without necessitating discontinuation of immunotherapy. The findings were …

Pd-L1 Expression On Circulating Tumor Cells May Be Predictive Of Response To Pembrolizumab In Advanced Melanoma: Results From A Pilot Study, Muhammad K. Khattak, Anna L. Reid, James Freeman, Michelle Pereira, Ashleigh Mcevoy, Johnny Lo, Markus Frank, Tarek Meniawy, Ali Didan, Isaac Spencer, Benhur Amanuel, Michael Millward, Mel Ziman, Elin Gray

Research outputs 2014 to 2021

BACKGROUND: PD-1 inhibitors are routinely used for the treatment of advanced melanoma. This study sought to determine whether PD-L1 expression on circulating tumor cells (CTCs) can serve as a predictive biomarker of clinical benefit and response to treatment with the PD-1 inhibitor pembrolizumab.

METHODS: Blood samples were collected from patients with metastatic melanoma receiving pembrolizumab, prior to treatment and 6-12 weeks after initiation of therapy. Multiparametric flow cytometry was used to identify CTCs and evaluate the expression of PD-L1.

RESULTS: CTCs were detected in 25 of 40 patients (63%). Patients with detectable PD-L1

CONCLUSION: Our results reveal the potential of …

Discordant Responses Between Primary Head And Neck Tumors And Nodal Metastases Treated With Neoadjuvant Nivolumab: Correlation Of Radiographic And Pathologic Treatment Effect., Dante J. Merlino, Jennifer M. Johnson, Madalina Tuluc, Stacey Gargano, Robert Stapp, Larry Harshyne, Benjamin E. Leiby, Adam Flanders, Ralph Zinner, Rita Axelrod, Joseph Curry, David M. Cognetti, Kyle Mannion, Young J. Kim, Ulrich Rodeck, Athanassios Argiris, Adam J. Luginbuhl

Department of Medical Oncology Faculty Papers

PD-1 blockade represents a promising treatment in patients with head and neck squamous cell carcinoma (HNSCC). We analyzed results of a neoadjuvant randomized window-of-opportunity trial of nivolumab plus/minus tadalafil to investigate whether immunotherapy-mediated treatment effects vary by site of involvement (primary tumor, lymph nodes) and determine how radiographic tumor shrinkage correlates with pathologic treatment effect.

Patients and Methods: Forty-four patients enrolled in trial NCT03238365 were treated with nivolumab 240 mg intravenously on days 1 and 15 with or without oral tadalafil, as determined by random assignment, followed by surgery on day 31. Radiographic volumetric response (RVR) was defined as percent …

Investigation Of The Functional Impact Of Anti-Pd-1 On Tumor-Infiltrating Lymphocytes (Til) And Mapping Of Tumor Genomic Features Relevant For Response To Til Therapy, Caitlin Creasy

Dissertations and Theses (Open Access)

With the growing use of both cellular and antibody-based immunotherapies, it has become more important to uncover biomarkers to predict patient response to therapy and ideally aid in patient selection for specific therapeutics, thereby enhancing treatment outcome. At MD Anderson, we have a 43% response rate to therapy when treating metastatic melanoma patients with adoptive cell therapy (ACT) of tumor-infiltrating lymphocytes (TIL), but it is unknown what makes the other 57% of patients not respond to therapy. It is further unknown how particularly early doses of checkpoint inhibitors, like anti-PD-1, attribute to TIL functionality, adding another confounding factor in determining …

A Narrative Review Of Targeted Therapy In Meningioma, Pituitary Adenoma, And Craniopharyngioma Of The Skull Base., Nina L. Martinez, Omaditya Khanna, Christopher J. Farrell

Department of Neurosurgery Faculty Papers

Management of solid tumors involving the skull base are primarily managed with surgery and radiation, though proximity to important vascular and neuroanatomic structures often limit the extent of resection and permissible radiation dose. Meningiomas are the most common primary brain tumor in adults, and although the majority of skull base meningiomas are low-grade, their location in proximity to critical anatomical structures precludes aggressive surgical resection, and larger tumors are often resistant to radiation treatment. In patients with clinically aggressive, unresectable meningiomas, several molecular biomarkers of angiogenesis, as well as genetic mutations (SMO, AKT1, PIK3CA, KLF4, POLR2, SMARCE1, and TRAF7), have …

A Pilot Study Comparing The Efficacy Of Lactate Dehydrogenase Levels Versus Circulating Cell-Free Micrornas In Monitoring Responses To Checkpoint Inhibitor Immunotherapy In Metastatic Melanoma Patients., Matias A Bustos, Rebecca Gross, Negin Rahimzadeh, Hunter Cole, Linh T Tran, Kevin Tran, Ling Takeshima, Stacey L Stern, Steven O'Day, Dave Hoon

Articles, Abstracts, and Reports

Serum lactate dehydrogenase (LDH) is a standard prognostic biomarker for stage IV melanoma patients. Often, LDH levels do not provide real-time information about the metastatic melanoma patients' disease status and treatment response. Therefore, there is a need to find reliable blood biomarkers for improved monitoring of metastatic melanoma patients who are undergoing checkpoint inhibitor immunotherapy (CII). The objective in this prospective pilot study was to discover circulating cell-free microRNA (cfmiR) signatures in the plasma that could assess melanoma patients' responses during CII. The cfmiRs were evaluated by the next-generation sequencing (NGS) HTG EdgeSeq microRNA (miR) Whole Transcriptome Assay (WTA; 2083 …

Clinical Application Of Oncolytic Viruses: A Systematic Review, Mary Cook, Aman Chauhan

Internal Medicine Faculty Publications

Leveraging the immune system to thwart cancer is not a novel strategy and has been explored via cancer vaccines and use of immunomodulators like interferons. However, it was not until the introduction of immune checkpoint inhibitors that we realized the true potential of immunotherapy in combating cancer. Oncolytic viruses are one such immunotherapeutic tool that is currently being explored in cancer therapeutics. We present the most comprehensive systematic review of all oncolytic viruses in Phase 1, 2, and 3 clinical trials published to date. We performed a systematic review of all published clinical trials indexed in PubMed that utilized oncolytic …

The Society For Immunotherapy Of Cancer (Sitc) Clinical Practice Guideline On Immunotherapy For The Treatment Of Acute Leukemia., Michael M Boyiadzis, Ivan Aksentijevich, Daniel A Arber, John Barrett, Renier J Brentjens, Jill Brufsky, Jorge Cortes, Marcos De Lima, Stephen J Forman, Ephraim J Fuchs, Linda J Fukas, Steven D Gore, Mark R Litzow, Jeffrey S Miller, John M Pagel, Edmund K Waller, Martin S Tallman

Articles, Abstracts, and Reports

Acute leukemia is a constellation of rapidly progressing diseases that affect a wide range of patients regardless of age or gender. Traditional treatment options for patients with acute leukemia include chemotherapy and hematopoietic cell transplantation. The advent of cancer immunotherapy has had a significant impact on acute leukemia treatment. Novel immunotherapeutic agents including antibody-drug conjugates, bispecific T cell engagers, and chimeric antigen receptor T cell therapies have efficacy and have recently been approved by the US Food and Drug Administration (FDA) for the treatment of patients with acute leukemia. The Society for Immunotherapy of Cancer (SITC) convened a panel of …

Hepatocellular Carcinoma-The Influence Of Immunoanatomy And The Role Of Immunotherapy, Keyur Patel, Ryan Lamm, Peter Altshuler, Hien Dang, Ashesh P. Shah, Md

Department of Surgery Faculty Papers

Hepatocellular carcinoma (HCC) is a leading cause of cancer-related morbidity and mortality worldwide. Most patients are diagnosed with advanced disease, limiting their options for treatment. While current treatments are adequate for lower staged disease, available systemic treatments are limited, with marginal benefit at best. Chimeric antigen receptor (CAR) T cell therapy, effective in treating liquid tumors such as B-cell lymphoma, presents a potentially promising treatment option for advanced HCC. However, new challenges specific to solid tumors, such as tumor immunoanatomy or the immune cell presence and position anatomically and the tumor microenvironment, need to be defined and overcome. Immunotherapy currently …

Therapeutic Trem2 Activation Ameliorates Amyloid-Beta Deposition And Improves Cognition In The 5xfad Model Of Amyloid Deposition, Brittani R. Price, Tiffany L. Sudduth, Erica M. Weekman, Sherika Johnson, Danielle Hawthorne, Abigail E. Woolums, Donna M. Wilcock

Sanders-Brown Center on Aging Faculty Publications

BACKGROUND: Triggering receptor expressed on myeloid cell-2 (TREM2) is a lipid and lipoprotein binding receptor expressed by cells of myeloid origin. Homozygous TREM2 mutations cause early onset progressive presenile dementia while heterozygous, point mutations triple the risk of Alzheimer's disease (AD). Although human genetic findings support the notion that loss of TREM2 function exacerbates neurodegeneration, it is not clear whether activation of TREM2 in a disease state would result in therapeutic benefits. To determine the viability of TREM2 activation as a therapeutic strategy, we sought to characterize an agonistic Trem2 antibody (AL002a) and test its efficacy and mechanism of action …

Impact Of Immunotherapy On The Survival Of Pancreatic Adenocarcinoma Patients: An Analysis Of The National Cancer Database, Saber A. Amin

Theses & Dissertations

Pancreatic adenocarcinoma (PDAC) represents 7.2% of all cancer deaths, and by 2030, it will become the second leading cause of death due to cancer. The median overall survival (OS) is 17-23 months in resectable and 4-6 months in metastatic PC [8-9]. The 5-year survival of resectable PC is 22%, and unresectable PC is 8%. A majority of patients treated with standard treatments such as surgery, chemotherapy, and radiation therapy eventually succumb to the disease due to widespread micrometastases at the time of diagnosis. Due to the minimal effect of the current treatments, novel treatment strategies such as immunotherapeutics have been …

Management And Treatment Of Hepatocellular Carcinoma With Immunotherapy: A Review Of Current And Future Options, Shima Ghavimi, Tehila Apfel, Hamed Azimi, Alana Persaud

Internal Medicine

With mortality rates of liver cancer doubling in the last 20 years, this disease is on the rise and has become the fifth most common cancer in men and the seventh most common cancer in women. Hepatocellular carcinoma (HCC) represents approximately 90% of all primary liver cancers and is a major global health concern. Patients with HCC can be managed curatively with surgical resection or with liver transplantation, if they are diagnosed at an early stage. Unfortunately, most patients with HCC present with advanced stages of the disease and have underlying liver dysfunction, which allows only 15% of patients to …

The Great Debate At 'Immunotherapy Bridge', Naples, December 5, 2019., Paolo A Ascierto, Carlo Bifulco, Jerome Galon, Claus Garbe, Samir N Khleif, Jennifer Mcquade, Kunle Odunsi, Hideho Okada, Chrystal M Paulos, Sergio A Quezada, Hussein A Tawbi, John Timmerman, Giorgio Trinchieri, Lisa H Butterfield, Igor Puzanov

Articles, Abstracts, and Reports

As part of the 2019 Immunotherapy Bridge congress (December 4-5, Naples, Italy), the Great Debate session featured counterpoint views from leading experts on six topical issues in immunotherapy today. These were the use of chimeric antigen receptor T cell therapy in solid tumors, whether the Immunoscore should be more widely used in clinical practice, whether antibody-dependent cellular cytotoxicity is important in the mode of action of anticytotoxic T-lymphocyte-associated protein 4 antibodies, whether the brain is immunologically unique or just another organ, the role of microbiome versus nutrition in affecting responses to immunotherapy, and whether chemotherapy is immunostimulatory or immunosuppressive. Discussion …

Chimeric Ad5.F35 Vector Evades Anti-Adenovirus Serotype 5 Neutralization Opposing Gucy2c-Targeted Antitumor Immunity, John C. Flickinger, Jagmohan Singh, Robert D Carlson, Elinor Leong, Trevor R. Baybutt, Joshua Barton, Ellen M. Caparosa, Amanda M. Pattison, Jeff A. Rappaport, Jamin Roh, Tingting Zhan, Babar Bashir, Scott A Waldman, Adam E. Snook

Department of Pharmacology and Experimental Therapeutics Faculty Papers

BACKGROUND: Adenovirus serotype 5 (Ad5) is a commonly used viral vector for transient delivery of transgenes, primarily for vaccination against pathogen and tumor antigens. However, endemic infections with Ad5 produce virus-specific neutralizing antibodies (NAbs) that limit transgene delivery and constrain target-directed immunity following exposure to Ad5-based vaccines. Indeed, clinical trials have revealed the limitations that virus-specific NAbs impose on the efficacy of Ad5-based vaccines. In that context, the emerging focus on immunological approaches targeting cancer self-antigens or neoepitopes underscores the unmet therapeutic need for more efficacious vaccine vectors.

METHODS: Here, we evaluated the ability of a chimeric adenoviral vector (Ad5.F35) …

Immunotherapy In Hepatocellular Cancer Patients With Mild To Severe Liver Dysfunction: Adjunctive Role Of The Albi Grade, David J Pinato, Takahiro Kaneko, Anwaar Saeed, Tiziana Pressiani, Ahmed Kaseb, Yinghong Wang, David Szafron, Tomi Jun, Sirish Dharmapuri, Abdul Rafeh Naqash, Mahvish Muzaffar, Musharraf Navaid, Chieh-Ju Lee, Anushi Bulumulle, Bo Yu, Sonal Paul, Neil Nimkar, Dominik Bettinger, Hannah Hildebrand, Yehia I Abugabal, Celina Ang, Thomas U Marron, Uqba Khan, Nicola Personeni, Lorenza Rimassa, Yi-Hsiang Huang

Faculty, Staff and Students Publications

Immune checkpoint inhibitors (ICI) have shown positive results in patients with hepatocellular carcinoma (HCC). As liver function contributes to prognosis, its precise assessment is necessary for the safe prescribing and clinical development of ICI in HCC. We tested the accuracy of the albumin-bilirubin (ALBI) grade as an alternative prognostic biomarker to the Child-Turcotte-Pugh (CTP). In a prospectively maintained multi-centre dataset of HCC patients, we assessed safety and efficacy of ICI across varying levels of liver dysfunction described by CTP (A to C) and ALBI grade and evaluated uni- and multi-variable predictors of overall (OS) and post-immunotherapy survival (PIOS). We studied …

Breast Cancer Treatment: Basics For The Primary Care Provider, Sarah Hirsh, Md

Department of Family & Community Medicine Presentations and Grand Rounds

Learning Objectives

1. To review the prevalence of breast cancer and the mortality rate of breast cancer in the United States.
2. To understand breast cancer staging and its role in prognostication.
3. To understand the therapies offered for the treatment of non-metastatic, invasive breast cancer and their side effects.
4. To review the role of the PCP in caring for patients undergoing treatment for breast cancer and those in remission.

Complete Response To Stage Iv Colorectal Adenocarcinoma With Disease-Free Survival At 24 Months: Case Report And Overview Of The Literature, Madison N. Crank 6746693, Arslan Iqbal, Michael Abdelmasseh, Mohamed Alsharedi, Doreen Griswold, Alysia Browne, Juan R. Sanabria

Marshall Journal of Medicine

Over 150,000 new cases of colon cancer were diagnosed in the US in 2019. Stage and age at diagnosis are important prognostic factors for overall survival (OS). For the age group 70-79, the OS for females with poorly differentiated stage IV colon cancer at 1, 2 and 5 years after surgery is 39%, 15%, and 2%, respectively. We present a case of a 77-year-old female with significant cardiac history. She was diagnosed with stage IV colorectal cancer complicated with enteric fistula. Due to her initial performance status and comorbidities, she was not a candidate for surgery or systemic chemotherapy. Nonetheless, …

Expression Of Tryptophan 2,3-Dioxygenase In Metastatic Uveal Melanoma, Mizue Terai, Eric R Londin, Ankit Rochani, Emma Link, Bao Lam, Gagan Kaushal, Alok Bhushan, Marlana Orloff, Takami Sato

Kimmel Cancer Center Faculty Papers

Uveal melanoma (UM) is the most common primary eye malignancy in adults and up to 50% of patients subsequently develop systemic metastasis. Metastatic uveal melanoma (MUM) is highly resistant to immunotherapy. One of the mechanisms for resistance would be the immune-suppressive tumor microenvironment. Here, we have investigated the role of tryptophan 2,3-dioxygenase (TDO) in UM. Both TDO and indoleamine 2,3-dioxygenase (IDO) catalyze tryptophan and produce kynurenine, which could cause inhibition of T cell immune responses. We first studied the expression of TDO on tumor tissue specimens obtained from UM hepatic metastasis. High expression of TDO protein was confirmed in all …

Observational Study Of Talimogene Laherparepvec Use In The Anti-Pd-1 Era For Melanoma In The Us (Cosmus-2), James Sun, Brian R. Gastman, Lucy Mccahon, Elizabeth I. Buchbinder, Igor Puzanov, Michele Nanni, James M. Lewis, Richard D. Carvajal, Shahnaz Singh-Kandah, Anupam M. Desai, Leon Raskin, Carrie M. Nielson, Rubina Ismail, Jonathan S. Zager

Oncologic Sciences Faculty Publications

Aim: Talimogene laherparepvec (T-VEC) is an intralesional therapy for unresectable, metastatic melanoma. T-VEC real-world use in the context of anti-PD1-based therapy requires further characterization.

Materials & methods: A retrospective review of T-VEC use from 1 January 2017 and 31 March 2018 for melanoma patients was conducted at seven US institutions.

Results: Among 83 patients, three categories of T-VEC and anti-PD-1 therapy were identified: T-VEC used without anti-PD-1 (n = 29, 35%), T-VEC after anti-PD-1-based therapy (n = 22, 27%) and concurrent T-VEC and anti-PD-1-based therapy (n = 32, 39%). 25% of patients discontinued T-VEC therapy due to no remaining injectable …

Prospective Molecular Profiling Of Circulating Tumor Cells From Patients With Melanoma Receiving Combinatorial Immunotherapy., Selena Y Lin, Shu-Ching Chang, Stella Lam, Romela Irene Ramos, Kevin Tran, Shuichi Ohe, Matthew P Salomon, Ali Asgar S Bhagat, Chwee Teck Lim, Trevan D Fischer, Leland J Foshag, Christine L Boley, Steven J O'Day, Dave Hoon

Articles, Abstracts, and Reports

BACKGROUND: Blood molecular profiling of circulating tumor cells (CTCs) can enable monitoring of patients with metastatic melanoma during checkpoint inhibitor immunotherapy (CII) and in combination with targeted therapies. We developed a microfluidics-based CTC platform to explore CTC profiling utility in CII-treated patients with melanoma using a melanoma messenger RNA (mRNA)/DNA biomarker panel.

METHODS: Blood samples (n = 213) were collected prospectively from 75 American Joint Committee on Cancer-staged III/IV melanoma patients during CII treatment and those enriched for CTCs. CTC profiling was performed using 5 known melanoma mRNA biomarkers and BRAF V600E DNA mutation. CTC biomarker status associations with clinical …

Immune-Mediated Colitis From Dual Checkpoint Inhibitors., Nishanth Thalambedu, Yasir Khan, Qian Zhang, Shristi Khanal, Ammar Ashfaq

Abington Jefferson Health Papers

Melanoma is a deadly disease with immunotherapy treatment options that emerged in the last few years and have changed the disease outcome. However, it is associated with immune-related toxic effects despite improving survival. We present the case of a 53-year-old woman who had two weeks of diarrhea after she was treated with dual immunotherapy agents for her advanced melanoma. The final workup revealed pancolitis, possibly due to immunotherapy adverse effects. Initial conservative treatment, unfortunately, did not lead to a clinical improvement until a steroid was introduced. We are reporting this case to alert our fellow physicians about the immune-mediated toxicities …

Hyperthermia And Immunotherapy: Clinical Opportunities., Mark D Hurwitz

Department of Radiation Oncology Faculty Papers

Hyperthermia holds great promise to advance immunotherapy in the treatment of cancer. Multiple trials have demonstrated benefit with the addition of hyperthermia to radiation or chemotherapy in the treatment of wide-ranging malignancies. Similarly, pre-clinical studies have demonstrated the ability of hyperthermia to enhance each of the 8 steps in the cancer-immunotherapy cycle including stimulation of tumor-specific immunity. While there has been an extensive recent focus on augmenting immunotherapy with radiation, surprisingly to date, there have been no clinical trials assessing the combination of hyperthermia with immunotherapy. The study of hyperthermia with immunotherapy is particularly compelling when considered in the context …

Relating The Gut Metagenome And Metatranscriptome To Immunotherapy Responses In Melanoma Patients., Brandilyn A. Peters, Melissa Wilson, Una Moran, Anna Pavlick, Allison Izsak, Todd Wechter, Jeffrey S. Weber, Iman Osman, Jiyoung Ahn

Department of Medical Oncology Faculty Papers

BACKGROUND: Recent evidence suggests that immunotherapy efficacy in melanoma is modulated by gut microbiota. Few studies have examined this phenomenon in humans, and none have incorporated metatranscriptomics, important for determining expression of metagenomic functions in the microbial community.

METHODS: In melanoma patients undergoing immunotherapy, gut microbiome was characterized in pre-treatment stool using 16S rRNA gene and shotgun metagenome sequencing (n = 27). Transcriptional expression of metagenomic pathways was confirmed with metatranscriptome sequencing in a subset of 17. We examined associations of taxa and metagenomic pathways with progression-free survival (PFS) using 500 × 10-fold cross-validated elastic-net penalized Cox regression.

RESULTS: Higher …

Multiple Sclerosis Outcomes After Cancer Immunotherapy, Catherine R. Garcia, Rani Jayswal, Val R. Adams, Lowell B. Anthony, John L. Villano

Markey Cancer Center Faculty Publications

INTRODUCTION: Neurological immune-related adverse events are a rare but potentially deadly complication after immune checkpoint inhibitor (ICI) treatment. As multiple sclerosis (MS) is an immune-mediated disease, it is unknown how ICI treatment may affect outcomes.

METHODS: We analyzed the United States Food and Drug Administration (FDA) Adverse Event Reporting System (FAERS) database for pembrolizumab, atezolizumab, nivolumab, ipilimumab, avelumab, and durvalumab 2 years prior their FDA approval until December 31, 2017, to include all cases with confirmed diagnosis/relapse of MS. We also included cases reported in the literature and a patient from our institution.

RESULTS: We identified 14 cases of MS …