Medicine and Health Sciences Commons^™

Identifying Personalized Metabolic Signatures In Breast Cancer., Priyanka Baloni, Wikum Dinalankara, John C Earls, Theo A Knijnenburg, Donald Geman, Luigi Marchionni, Nathan D Price

Articles, Abstracts, and Reports

Cancer cells are adept at reprogramming energy metabolism, and the precise manifestation of this metabolic reprogramming exhibits heterogeneity across individuals (and from cell to cell). In this study, we analyzed the metabolic differences between interpersonal heterogeneous cancer phenotypes. We used divergence analysis on gene expression data of 1156 breast normal and tumor samples from The Cancer Genome Atlas (TCGA) and integrated this information with a genome-scale reconstruction of human metabolism to generate personalized, context-specific metabolic networks. Using this approach, we classified the samples into four distinct groups based on their metabolic profiles. Enrichment analysis of the subsystems indicated that amino …

Genetic Variants In Immune Related Genes As Predictors Of Responsiveness To Bcg Immunotherapy In Metastatic Melanoma Patients., Romela Irene Ramos, Misa A Shaw, Leland J Foshag, Stacey L Stern, Negin Rahimzadeh, David Elashoff, Dave Hoon

Articles, Abstracts, and Reports

Adjuvant immunotherapy in melanoma patients improves clinical outcomes. However, success is unpredictable due to inherited heterogeneity of immune responses. Inherent immune genes associated with single nucleotide polymorphisms (SNPs) may influence anti-tumor immune responses. We assessed the predictive ability of 26 immune-gene SNPs genomic panels for a clinical response to adjuvant BCG (Bacillus Calmette-Guérin) immunotherapy, using melanoma patient cohorts derived from three phase III multicenter clinical trials: AJCC (American Joint Committee on Cancer) stage IV patients given adjuvant BCG (pilot cohort; n = 92), AJCC stage III patients given adjuvant BCG (verification cohort; n = 269), and …

Genetic Variants In Immune Related Genes As Predictors Of Responsiveness To Bcg Immunotherapy In Metastatic Melanoma Patients., Romela Irene Ramos, Misa A Shaw, Leland Foshag, Stacey L Stern, Negin Rahimzadeh, David Elashoff, Dave Hoon

Articles, Abstracts, and Reports

Adjuvant immunotherapy in melanoma patients improves clinical outcomes. However, success is unpredictable due to inherited heterogeneity of immune responses. Inherent immune genes associated with single nucleotide polymorphisms (SNPs) may influence anti-tumor immune responses. We assessed the predictive ability of 26 immune-gene SNPs genomic panels for a clinical response to adjuvant BCG (Bacillus Calmette-Guérin) immunotherapy, using melanoma patient cohorts derived from three phase III multicenter clinical trials: AJCC (American Joint Committee on Cancer) stage IV patients given adjuvant BCG (pilot cohort; n = 92), AJCC stage III patients given adjuvant BCG (verification cohort; n = 269), and …

Development And Preliminary Clinical Activity Of Pd-1-Guided Ctla-4 Blocking Bispecific Dart Molecule., Alexey Berezhnoy, Bradley J Sumrow, Kurt Stahl, Kalpana Shah, Daorong Liu, Jonathan Li, Su-Shin Hao, Anushka De Costa, Sanjeev Kaul, Johanna Bendell, Gregory M Cote, Jason J Luke, Rachel E Sanborn, Manish R Sharma, Francine Chen, Hua Li, Gundo Diedrich, Ezio Bonvini, Paul A Moore

Articles, Abstracts, and Reports

Combination immunotherapy with antibodies directed against PD-1 and CTLA-4 shows improved clinical benefit across cancer indications compared to single agents, albeit with increased toxicity. Leveraging the observation that PD-1 and CTLA-4 are co-expressed by tumor-infiltrating lymphocytes, an investigational PD-1 x CTLA-4 bispecific DART molecule, MGD019, is engineered to maximize checkpoint blockade in the tumor microenvironment via enhanced CTLA-4 blockade in a PD-1-binding-dependent manner.

Modulation Of Immune Checkpoints By Chemotherapy In Human Colorectal Liver Metastases., Neda Jabbari, Heidi L Kenerson, Christopher Lausted, Xiaowei Yan, Changting Meng, Kevin M Sullivan, Priyanka Baloni, Dani E Bergey, Venu G Pillarisetty, Leroy Hood, Raymond S Yeung, Qiang Tian

Articles, Abstracts, and Reports

Metastatic colorectal cancer (CRC) is a major cause of cancer-related death, and incidence is rising in younger populations (younger than 50 years). Current chemotherapies can achieve response rates above 50%, but immunotherapies have limited value for patients with microsatellite-stable (MSS) cancers. The present study investigates the impact of chemotherapy on the tumor immune microenvironment. We treat human liver metastases slices with 5-fluorouracil (5-FU) plus either irinotecan or oxaliplatin, then perform single-cell transcriptome analyses. Results from eight cases reveal two cellular subtypes with divergent responses to chemotherapy. Susceptible tumors are characterized by a stemness signature, an activated interferon pathway, and suppression …

Erratum: Viswanathan, A., Et Al. Battling Glioblastoma: A Novel Tyrosine Kinase Inhibitor With Multi-Dimensional Anti-Tumor Effect (Running Title: Cancer Cells Death Signalling Activation)., Anisha Viswanathan, Aliyu Musa, Akshaya Murugesan, João R Vale, Carlos A M Afonso, Saravanan Konda Mani, Olli Yli-Harja, Nuno R Candeias, Meenakshisundaram Kandhavelu

Articles, Abstracts, and Reports

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Sitc Cancer Immunotherapy Resource Document: A Compass In The Land Of Biomarker Discovery., Siwen Hu-Lieskovan, Srabani Bhaumik, Kavita Dhodapkar, Jean-Charles J B Grivel, Sumati Gupta, Brent A Hanks, Sylvia Janetzki, Thomas O Kleen, Yoshinobu Koguchi, Amanda W Lund, Cristina Maccalli, Yolanda D Mahnke, Ruslan D Novosiadly, Senthamil R Selvan, Tasha Sims, Yingdong Zhao, Holden T Maecker

Articles, Abstracts, and Reports

Since the publication of the Society for Immunotherapy of Cancer's (SITC) original cancer immunotherapy biomarkers resource document, there have been remarkable breakthroughs in cancer immunotherapy, in particular the development and approval of immune checkpoint inhibitors, engineered cellular therapies, and tumor vaccines to unleash antitumor immune activity. The most notable feature of these breakthroughs is the achievement of durable clinical responses in some patients, enabling long-term survival. These durable responses have been noted in tumor types that were not previously considered immunotherapy-sensitive, suggesting that all patients with cancer may have the potential to benefit from immunotherapy. However, a persistent challenge in …

Society For Immunotherapy Of Cancer Clinical And Biomarkers Data Sharing Resource Document: Volume Ii-Practical Challenges., Alessandra Cesano, Michael A Cannarile, Sacha Gnjatic, Bruno Gomes, Justin Guinney, Vaios Karanikas, Mohan Karkada, John M Kirkwood, Beatrix Kotlan, Giuseppe V Masucci, Els Meeusen, Anne Monette, Aung Naing, Vésteinn Thorsson, Nicholas Tschernia, Ena Wang, Daniel K Wells, Timothy L Wyant, Sergio Rutella

Articles, Abstracts, and Reports

The development of strongly predictive validated biomarkers is essential for the field of immuno-oncology (IO) to advance. The highly complex, multifactorial data sets required to develop these biomarkers necessitate effective, responsible data-sharing efforts in order to maximize the scientific knowledge and utility gained from their collection. While the sharing of clinical- and safety-related trial data has already been streamlined to a large extent, the sharing of biomarker-aimed clinical trial derived data and data sets has been met with a number of hurdles that have impaired the progression of biomarkers from hypothesis to clinical use. These hurdles include technical challenges associated …

A Rare Case Of Idiopathic Pyometra In A Premenopausal Patient., Kristina M Mori, Howard D Epstein, Michael C Roossin, Bram H Goldstein

Articles, Abstracts, and Reports

Pyometra is a very uncommon disease principally occurring in postmenopausal women. It is characterized by the accumulation of purulent material within the uterine cavity. This paper presents the clinical history of a 35-year-old premenopausal woman with otherwise normal menstruation who developed heavy menstruation and was diagnosed with a benign pyometra of indeterminate etiology in March 2017. The patient underwent repeated ultrasound-guided drainage, dilation and curettage, and antibiotic therapy. Biopsies of the pelvic sidewall revealed endometriosis in June 2017. The heavy menstruation and suppurative fluid in the uterus of the patient persisted in which intramuscular leuprolide acetate was prescribed to address …

Pomalidomide, Dexamethasone, And Daratumumab In Relapsed Refractory Multiple Myeloma After Lenalidomide Treatment., David S Siegel, Gary J Schiller, Christy Samaras, Michael Sebag, Jesus Berdeja, Siddhartha Ganguly, Jeffrey Matous, Kevin Song, Christopher S Seet, Giampaolo Talamo, Mirelis Acosta-Rivera, Michael Bar, Donald Quick, Bertrand Anz, Gustavo Fonseca, Donna Reece, William E Pierceall, Weiyuan Chung, Faiza Zafar, Amit Agarwal, Nizar J Bahlis

Articles, Abstracts, and Reports

Patients with multiple myeloma who have relapsed after or become refractory to lenalidomide in early treatment lines represent a clinically important population in need of effective therapies. The safety and efficacy of pomalidomide, low-dose dexamethasone, and daratumumab was evaluated in lenalidomide-pretreated patients with relapsed or refractory multiple myeloma (RRMM) after one to two prior treatment lines in the phase 2 MM-014 study. Patients received pomalidomide 4 mg daily from days 1-21 and dexamethasone 40 mg weekly (28-day cycles). Daratumumab 16 mg/kg was administered per label. Primary endpoint was overall response rate (ORR); secondary endpoints included progression-free survival (PFS) and safety. …

Predicting Breast Cancer Response To Neoadjuvant Treatment Using Multi-Feature Mri: Results From The I-Spy 2 Trial., Wen Li, David C Newitt, Jessica Gibbs, Lisa J Wilmes, Ella F Jones, Vignesh A Arasu, Fredrik Strand, Natsuko Onishi, Alex Anh-Tu Nguyen, John Kornak, Bonnie N Joe, Elissa R Price, Haydee Ojeda-Fournier, Mohammad Eghtedari, Kathryn W Zamora, Stefanie A Woodard, Heidi Umphrey, Wanda Bernreuter, Michael Nelson, An Ly Church, Patrick Bolan, Theresa Kuritza, Kathleen Ward, Kevin Morley, Dulcy Wolverton, Kelly Fountain, Dan Lopez-Paniagua, Lara Hardesty, Kathy Brandt, Elizabeth S Mcdonald, Mark Rosen, Despina Kontos, Hiroyuki Abe, Deepa Sheth, Erin P Crane, Charlotte Dillis, Pulin Sheth, Linda Hovanessian-Larsen, Dae Hee Bang, Bruce Porter, Karen Y Oh, Neda Jafarian, Alina Tudorica, Bethany L Niell, Jennifer Drukteinis, Mary S Newell, Michael A Cohen, Marina Giurescu, Elise Berman, Constance Lehman, Savannah C Partridge, Kimberly A Fitzpatrick, Marisa H Borders, Wei T Yang, Basak Dogan, Sally Goudreau, Thomas Chenevert, Christina Yau, Angela Demichele, Don Berry, Laura J Esserman, Nola M Hylton

Articles, Abstracts, and Reports

Dynamic contrast-enhanced (DCE) MRI provides both morphological and functional information regarding breast tumor response to neoadjuvant chemotherapy (NAC). The purpose of this retrospective study is to test if prediction models combining multiple MRI features outperform models with single features. Four features were quantitatively calculated in each MRI exam: functional tumor volume, longest diameter, sphericity, and contralateral background parenchymal enhancement. Logistic regression analysis was used to study the relationship between MRI variables and pathologic complete response (pCR). Predictive performance was estimated using the area under the receiver operating characteristic curve (AUC). The full cohort was stratified by hormone receptor (HR) and …

Breast Cancer Distant Recurrence Lead Time Interval By Detection Method In An Institutional Cohort., Henry G Kaplan, Judith A Malmgren, Mary K Atwood

Articles, Abstracts, and Reports

BACKGROUND: Lead time, the interval between screen detection and when a disease would have become clinically evident, has been cited to explain longer survival times in mammography detected breast cancer cases (BC).

METHODS: An institutional retrospective cohort study of BC outcomes related to detection method (mammography (MamD) vs. patient (PtD)). Cases were first primary invasive stage I-III BC, age 40-74 years (n = 6603), 1999-2016. Survival time was divided into 1) distant disease-free interval (DDFI) and 2) distant disease-specific survival (DDSS) as two separate time interval outcomes. We measured statistical association between detection method and diagnostic, treatment and outcome variables …

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 …

Discovery Of Driver Non-Coding Splice-Site-Creating Mutations In Cancer., Song Cao, Daniel Cui Zhou, Clara Oh, Reyka G Jayasinghe, Yanyan Zhao, Christopher J Yoon, Matthew A Wyczalkowski, Matthew H Bailey, Terrence Tsou, Qingsong Gao, Andrew Malone, Sheila Reynolds, Ilya Shmulevich, Michael C Wendl, Feng Chen, Li Ding

Articles, Abstracts, and Reports

Non-coding mutations can create splice sites, however the true extent of how such somatic non-coding mutations affect RNA splicing are largely unexplored. Here we use the MiSplice pipeline to analyze 783 cancer cases with WGS data and 9494 cases with WES data, discovering 562 non-coding mutations that lead to splicing alterations. Notably, most of these mutations create new exons. Introns associated with new exon creation are significantly larger than the genome-wide average intron size. We find that some mutation-induced splicing alterations are located in genes important in tumorigenesis (ATRX, BCOR, CDKN2B, MAP3K1, MAP3K4, MDM2, SMAD4, STK11, TP53 etc.), often leading …

An Atypical Case Of Necrotizing Fasciitis Secondary To Perforated Cecal Cancer., Laura S Heidelberg, Erica Pettke, Teresa E Wagner, Lauren Angotti

Articles, Abstracts, and Reports

Necrotizing fasciitis is an aggressive, life threatening soft tissue infection that requires high index of suspicion for diagnosis. Diagnosis is clinical with management including broad spectrum antibiotics and emergent operative debridement. The majority of cases are secondary to underlying medical processes, local tissue damage, abscess, or inciting procedure, with a paucity of data correlating causation with colon cancer. We describe the case of an 84-year-old man presenting with sepsis of unknown origin who was diagnosed with an atypical presentation of necrotizing fasciitis secondary to a perforated cecal malignancy. His case is unique in that a less virulent polymicrobial infection was …

Tp53 Abnormalities Correlate With Immune Infiltration And Associate With Response To Flotetuzumab Immunotherapy In Aml., Jayakumar Vadakekolathu, Catherine Lai, Stephen Reeder, Sarah E Church, Tressa Hood, Anbarasu Lourdusamy, Michael P Rettig, Ibrahim Aldoss, Anjali S Advani, John E Godwin, Matthew J Wieduwilt, Martha Arellano, John Muth, Tung On Yau, Farhad Ravandi, Kendra Sweet, Heidi Altmann, Gemma A Foulds, Friedrich Stölzel, Jan Moritz Middeke, Marilena Ciciarello, Antonio Curti, Peter J M Valk, Bob Löwenberg, Ivana Gojo, Martin Bornhäuser, John F Dipersio, Jan K Davidson-Moncada, Sergio Rutella

Articles, Abstracts, and Reports

Somatic TP53 mutations and 17p deletions with genomic loss of TP53 occur in 37% to 46% of acute myeloid leukemia (AML) with adverse-risk cytogenetics and correlate with primary induction failure, high risk of relapse, and dismal prognosis. Herein, we aimed to characterize the immune landscape of TP53-mutated AML and determine whether TP53 abnormalities identify a patient subgroup that may benefit from immunotherapy with flotetuzumab, an investigational CD123 × CD3 bispecific dual-affinity retargeting antibody (DART) molecule. The NanoString PanCancer IO360 assay was used to profile 64 diagnostic bone marrow (BM) samples from patients with TP53-mutated (n = 42) and TP53-wild-type (TP53-WT) …

Targeting Breast Cancer Metabolism With A Novel Inhibitor Of Mitochondrial Atp Synthesis., Myoung Sook Kim, Ramkishore Gernapudi, Yessenia Cedeño Cedeño, Brian M Polster, Ramon Martinez, Paul Shapiro, Santosh Kesari, Elmar Nurmemmedov, Antonino Passaniti

Articles, Abstracts, and Reports

Inhibitors of mitochondrial respiration and ATP synthesis may promote the selective killing of respiration-competent cancer cells that are critical for tumor progression. We previously reported that CADD522, a small molecule inhibitor of the RUNX2 transcription factor, has potential for breast cancer treatment. In the current study, we show that CADD522 inhibits mitochondrial oxidative phosphorylation by decreasing the mitochondrial oxygen consumption rate (OCR) and ATP production in human breast cancer cells in a RUNX2-independent manner. The enzyme activity of mitochondrial ATP synthase was inhibited by CADD522 treatment. Importantly, results from cellular thermal shift assays that detect drug-induced protein stabilization revealed that …

Tp53 Abnormalities Correlate With Immune Infiltration And Associate With Response To Flotetuzumab Immunotherapy In Aml., Jayakumar Vadakekolathu, Catherine Lai, Stephen Reeder, Sarah E Church, Tressa Hood, Anbarasu Lourdusamy, Michael P Rettig, Ibrahim Aldoss, Anjali S Advani, John E Godwin, Matthew J Wieduwilt, Martha Arellano, John Muth, Tung On Yau, Farhad Ravandi, Kendra Sweet, Heidi Altmann, Gemma A Foulds, Friedrich Stölzel, Jan Moritz Middeke, Marilena Ciciarello, Antonio Curti, Peter J M Valk, Bob Löwenberg, Ivana Gojo, Martin Bornhäuser, John F Dipersio, Jan K Davidson-Moncada, Sergio Rutella

Articles, Abstracts, and Reports

Somatic TP53 mutations and 17p deletions with genomic loss of TP53 occur in 37% to 46% of acute myeloid leukemia (AML) with adverse-risk cytogenetics and correlate with primary induction failure, high risk of relapse, and dismal prognosis. Herein, we aimed to characterize the immune landscape of TP53-mutated AML and determine whether TP53 abnormalities identify a patient subgroup that may benefit from immunotherapy with flotetuzumab, an investigational CD123 × CD3 bispecific dual-affinity retargeting antibody (DART) molecule. The NanoString PanCancer IO360 assay was used to profile 64 diagnostic bone marrow (BM) samples from patients with TP53-mutated (n = 42) and TP53-wild-type (TP53-WT) …

Navigating The Paradox Of Scarcity: The Case For Radiologist-Driven Care., Daniel A Ortiz, Kevin M Cregan, Join Y Luh, Taj M Kattapuram

Articles, Abstracts, and Reports

No abstract provided.

No Time To Die: The Consensus Immunoscore For Predicting Survival And Response To Chemotherapy Of Locally Advanced Colon Cancer Patients In A Multicenter International Study., Paolo A Ascierto, Francesco M Marincola, Bernard A Fox, Jérôme Galon

Articles, Abstracts, and Reports

The multicenter international Society for Immunotherapy of Cancer (SITC) study of the consensus Immunoscore demonstrated the prediction of survival and response to chemotherapy in 763 Stage III colon cancer (CC) patients. Similar Immunoscore groups were found in elderly patients, and densities of immune cells and intratumoral T-cell repertoire were not decreasing with age in the tumor microenvironment. In two independent cohorts, Immunoscore significantly predicted time to recurrence (TTR), disease-free survival (DFS), and overall survival (OS), including within high-risk (T4 or N2) and low-risk (T1-3, N1) patients. In stratified Cox multivariable analysis for TTR, DFS, and OS, Immunoscore's association to outcomes …

Feasibility Of Treating High Grade Gliomas In Children With Tumor-Treating Fields: A Case Series., John Crawford, Marlon G Saria, Girish Dhall, Ashley Margol, Santosh Kesari

Articles, Abstracts, and Reports

Children diagnosed with high grade gliomas (HGG) have dismal prognoses and treatment options remain limited. Tumor treating fields (TTFields) in combination with temozolomide (TMZ) is approved for the treatment of newly diagnosed and recurrent glioblastoma (GBM) in adult patients. However, clinical experience with TTFields in the pediatric HGG population is lacking. This retrospective review of four clinical cases was undertaken to evaluate the feasibility of treating children diagnosed with HGG off-label with TTFields. Patients were evaluated for device compliance, safety, and outcome. Treatment with TTFields was delivered via four transducer arrays placed on the shaved scalp, which were connected to …

Society For Immunotherapy Of Cancer Clinical And Biomarkers Data Sharing Resource Document: Volume I-Conceptual Challenges., Sergio Rutella, Michael A Cannarile, Sacha Gnjatic, Bruno Gomes, Justin Guinney, Vaios Karanikas, Mohan Karkada, John M Kirkwood, Beatrix Kotlan, Giuseppe V Masucci, Els Meeusen, Anne Monette, Aung Naing, Vésteinn Thorsson, Nicholas Tschernia, Ena Wang, Daniel K Wells, Timothy L Wyant, Alessandra Cesano

Articles, Abstracts, and Reports

The sharing of clinical trial data and biomarker data sets among the scientific community, whether the data originates from pharmaceutical companies or academic institutions, is of critical importance to enable the development of new and improved cancer immunotherapy modalities. Through data sharing, a better understanding of current therapies in terms of their efficacy, safety and biomarker data profiles can be achieved. However, the sharing of these data sets involves a number of stakeholder groups including patients, researchers, private industry, scientific journals and professional societies. Each of these stakeholder groups has differing interests in the use and sharing of clinical trial …

Untargeted Longitudinal Analysis Of A Wellness Cohort Identifies Markers Of Metastatic Cancer Years Prior To Diagnosis., Andrew T Magis, Noa Rappaport, Matthew P Conomos, Gilbert S Omenn, Jennifer C Lovejoy, Leroy Hood, Nathan D Price

Articles, Abstracts, and Reports

We analyzed 1196 proteins in longitudinal plasma samples from participants in a commercial wellness program, including samples collected pre-diagnosis from ten cancer patients and 69 controls. For three individuals ultimately diagnosed with metastatic breast, lung, or pancreatic cancer, CEACAM5 was a persistent longitudinal outlier as early as 26.5 months pre-diagnosis. CALCA, a biomarker for medullary thyroid cancer, was hypersecreted in metastatic pancreatic cancer at least 16.5 months pre-diagnosis. ERBB2 levels spiked in metastatic breast cancer between 10.0 and 4.0 months pre-diagnosis. Our results support the value of deep phenotyping seemingly healthy individuals in prospectively inferring disease transitions.

Nivolumab In Advanced Hepatocellular Carcinoma: Safety Profile And Select Treatment-Related Adverse Events From The Checkmate 040 Study., Karen Julien, Hiu Tung Leung, Carmen Fuertes, Megumi Mori, Miao-Jen Wang, Jocelyn Teo, Lisa Weiss, Sara Hamilton, Holly Difebo, Yoon Jin Noh, Aralee Galway, Jane Koh, Edith Brutcher, Huanyu Zhao, Yun Shen, Marina Tschaika, Yue-Yun To

Articles, Abstracts, and Reports

BACKGROUND: CheckMate 040 assessed the efficacy and safety of nivolumab in patients with advanced hepatocellular carcinoma (HCC). Understanding the safety profile of nivolumab is needed to support the management of treatment-related adverse events (TRAEs). This analysis assessed the safety of nivolumab monotherapy in the phase I/II, open-label CheckMate 040 study.

MATERIALS AND METHODS: Select TRAEs (sTRAEs; TRAEs with potential immunologic etiology requiring more frequent monitoring) occurring between first dose and 30 days after last dose were analyzed in patients in the dose-escalation and -expansion phases. Time to onset (TTO), time to resolution (TTR), and recurrence of sTRAEs were assessed, and …

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 …

Lenvatinib Plus Pembrolizumab In Patients With Advanced Endometrial Cancer., Vicky Makker, Matthew H Taylor, Carol Aghajanian, Ana Oaknin, James Mier, Allen L Cohn, Margarita Romeo, Raquel Bratos, Marcia S Brose, Christopher Disimone, Mark Messing, Daniel E Stepan, Corina E Dutcus, Jane Wu, Emmett V Schmidt, Robert Orlowski, Pallavi Sachdev, Robert Shumaker, Antonio Casado Herraez

Articles, Abstracts, and Reports

PURPOSE: Patients with advanced endometrial carcinoma have limited treatment options. We report final primary efficacy analysis results for a patient cohort with advanced endometrial carcinoma receiving lenvatinib plus pembrolizumab in an ongoing phase Ib/II study of selected solid tumors.

METHODS: Patients took lenvatinib 20 mg once daily orally plus pembrolizumab 200 mg intravenously once every 3 weeks, in 3-week cycles. The primary end point was objective response rate (ORR) at 24 weeks (ORR

RESULTS: At data cutoff, 108 patients with previously treated endometrial carcinoma were enrolled, with a median follow-up of 18.7 months. The ORR

CONCLUSION: Lenvatinib plus pembrolizumab showed …

Perspectives In Melanoma: Meeting Report From The "Melanoma Bridge" (December 5th-7th, 2019, Naples, Italy)., Paolo A Ascierto, Igor Puzanov, Sanjiv S Agarwala, Christian Blank, Richard D Carvajal, Sandra Demaria, Reinhard Dummer, Marc Ernstoff, Soldano Ferrone, Bernard A Fox, Thomas F Gajewski, Claus Garbe, Patrick Hwu, Roger S Lo, Georgina V Long, Jason J Luke, Iman Osman, Michael A Postow, Ryan J Sullivan, Janis M Taube, Giorgio Trinchieri, Hassane M Zarour, Corrado Caracò, Magdalena Thurin

Articles, Abstracts, and Reports

The melanoma treatment landscape changed in 2011 with the approval of the first anti-cytotoxic T-lymphocyte-associated protein (CTLA)-4 checkpoint inhibitor and of the first BRAF-targeted monoclonal antibody, both of which significantly improved overall survival (OS). Since then, improved understanding of the tumor microenvironment (TME) and tumor immune-evasion mechanisms has resulted in new approaches to targeting and harnessing the host immune response. The approval of new immune and targeted therapies has further improved outcomes for patients with advanced melanoma and other combination modalities are also being explored such as chemotherapy, radiotherapy, electrochemotherapy and surgery. In addition, different strategies of drugs administration including …

Sequential Complications Of Hypercalcemia, Necrotizing Granulomatous Vasculitis, And Aplastic Anemia Occurring In One Patient With Angioimmunoblastic T-Cell Lymphoma., Sriman Swarup, Jonathan Kopel, Kyaw Zin Thein, Kaiser Tarafdar, Khatrina Swarup, Seshadri Thirumala, Donald P Quick

Articles, Abstracts, and Reports

In this case report of a patient with angioimmunoblastic T-cell lymphoma (AITL), we describe the occurrence of three sequential complications that have been reported uncommonly in this disease subtype. Firstly, the patient developed hypercalcemia due to elevated 1,25-didydroxyvitamin D. Although hypercalcemia in AITL is not rare (1-2% incidence), this case was unusual in that the complication developed when disease appeared stable and symptomatically, he was doing well otherwise. Hypercalcemia surprisingly resolved a few months later at a time when his disease appeared to be progressing. A year later, the patient presented with digital ischemia necessitating partial amputation of a finger. …

Neoantigen-Specific Cd4(+) T-Cell Response Is Critical For The Therapeutic Efficacy Of Cryo-Thermal Therapy, Peng Peng, Hong-Ming Hu, Ping Liu, Lisa X Xu

Articles, Abstracts, and Reports

Background: Traditional tumor thermal ablations, such as radiofrequency ablation (RFA) and cryoablation, can result in good local control of tumor, but traditional tumor thermal ablations are limited by poor long-term survival due to the failure of control of distal metastasis. Our previous studies developed a novel cryo-thermal therapy to treat the B16F10 melanoma mouse model. Long-term survival and T-cell-mediated durable antitumor immunity were achieved after cryo-thermal therapy, but whether tumor antigen-specific T-cells were augmented by cryo-thermal therapy was not determined.

Methods: The long-term antitumor therapeutic efficacy of cryo-thermal therapy was performed in B16F10 murine melanoma models. Splenocytes derived from mice …

Efficacy And Safety Of First-Line Avelumab In Patients With Advanced Non-Small Cell Lung Cancer: Results From A Phase Ib Cohort Of The Javelin Solid Tumor Study., Claire F Verschraegen, Guy Jerusalem, Edward F Mcclay, Nicholas Iannotti, Charles H Redfern, Jaafar Bennouna, Franklin L Chen, Karen Kelly, Janice Mehnert, John C Morris, Matthew H Taylor, David Spigel, Ding Wang, Hans Juergen Grote, Dongli Zhou, Neru Munshi, Marcis Bajars, James L Gulley

Articles, Abstracts, and Reports

INTRODUCTION: Avelumab, an antiprogrammed death ligand-1 antibody, is approved as a monotherapy for treatment of metastatic Merkel cell carcinoma and advanced urothelial carcinoma, and in combination with axitinib for advanced renal cell carcinoma. We report the efficacy and safety of first-line avelumab in advanced non-small cell lung cancer (NSCLC).

METHODS: In a phase I expansion cohort of the JAVELIN Solid Tumor trial, patients with treatment-naive, metastatic, or recurrent NSCLC received 10 mg/kg avelumab intravenously every 2 weeks. Endpoints included best overall response, duration of response (DOR), progression-free survival (PFS), overall survival (OS), and safety.

RESULTS: Overall, 156 patients were enrolled …