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Articles by Matthew D. Hellmann
Lineage tracing reveals clonal progenitors and long-term persistence of tumor-specific T cells during immune checkpoint blockade
Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY, USA Weill Cornell Medical College, New York, NY, USA Parker Institute for Cancer Immunotherapy, Memorial Sloan Kettering Cancer Center, New York, NY, USA Ludwig Collaborative and Swim Across America Laboratory, Memorial Sloan Kettering Cancer Center, New York, NY, USA Human Oncology and Pathogenesis Program, Memorial Sloan Kettering Cancer Center, New York, NY, USA
Author Correction: Fundamental immune–oncogenicity trade-offs define driver mutation fitness - Nature
Correction to: Nature https://doi.org/10.1038/s41586-022-4696-z,published online 11 May 2022. In the version of this article initially published, the surname of author Chaitanya Bandlamudi was misspelt as Bandlamundi. The error has been corrected in the HTML and PDF versions of the article Author information Author notes These authors contributed equally: David Hoyos, Roberta Zappasodi These authors jointly supervised this work: Taha Merghoub, Arnold J. Levine, Marta Łuksza, Benjamin D.
Fundamental immune–oncogenicity trade-offs define driver mutation fitness - Nature
Abstract Missense driver mutations in cancer are concentrated in a few hotspots1. Various mechanisms have been proposed to explain this skew, including biased mutational processes2, phenotypic differences3,4,5,6 and immunoediting of neoantigens7,8; however, to our knowledge, no existing model weighs the relative contribution of these features to tumour evolution.
Immune-related cutaneous adverse events (ircAEs) represent a significant clinical problem in cancer checkpoint inhibitor (CPI) therapy, the most rapidly growing cancer treatment. Mechanisms of CPI induced ircAE immunologic endotypes and their association with polarized immune responses have not been examined.
First-Line Immunotherapy for Non-Small-Cell Lung Cancer
First-Line Immunotherapy for Non–Small-Cell Lung Cancer The following represents disclosure information provided by authors of this manuscript. All relationships are considered compensated unless otherwise noted. Relationships are self-held unless noted. I = Immediate Family Member, Inst = My Institution. Relationships may not relate to the subject matter of this manuscript.
Insights from prospective multi-omic profiling of lymphocytes in resected lung cancer
In this issue of Annals, Federico and colleagues report prospectively collected multi-omic data from 150 patients with localized non-small cell lung cancer (NSCLC) who underwent resection at the MD Anderson Cancer Center from 2016-2018 (ICON cohort) ( 1 L. Federico et al., Distinct tumor-infiltrating lymphocyte landscapes are associated with clinical outcomes in localized non-small cell lung cancer. Ann Oncol 2022; 33: https://doi.org/10.1016/j.annonc.2021.09.021 ).
Inherited PD-1 deficiency underlies tuberculosis and autoimmunity in a child - Nature Medicine
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Abstract The pathophysiology of adverse events following programmed cell death protein 1 (PD-1) blockade, including tuberculosis (TB) and autoimmunity, remains poorly characterized. We studied a patient with inherited PD-1 deficiency and TB who died of pulmonary autoimmunity. The patient’s leukocytes did not express PD-1 or respond to PD-1-mediated suppression.
By Masato Ogishi, Caner Aytekin, David Langlais, Mathieu Bourgey, Peng Zhang, Simon J. Pelham, András N. Spaan, Jérémie Rosain, Matthew D. Hellmann, Margaret K. Callahan, Matthew Adamow, Phillip Wong, Jedd D. Wolchok, Cindy S. Ma, Jean-François Emile, Michael Glickman, Deniz Çağdaş, Vivien Béziat, Silvia Vilarinho Verified, Bertrand Boisson, Nico Marr, Luigi D. Notarangelo, Stuart G. Tangye, Tasuku Honjo, Philippe Gros, Stephanie Boisson-Dupuis, Yuka Nakajima
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Nature
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Brief Report: Association Between Early-Discontinuation of Durvalumab and Poor Survival in Patients with Stage III Non-Small Cell Lung Cancer
This paper is only available as a PDF. To read, Please Download here. Abstract: Introduction Durvalumab after concurrent chemoradiation (cCRT) has been found to improve outcomes of patients with unresected stage III NSCLC. However, the survival impact of discontinuing durvalumab early due to adverse events (AEs) remains unknown. Methods Patients with stage III NSLCC treated with cCRT, and ≥1 dose of durvalumab across a multi-site cancer center were examined.
Translating inspiration from COVID-19 vaccine trials to innovations in clinical cancer research
Main text The operational efficiencies which led to the rapid approval of effective vaccines for COVID-19 inspire lessons in innovation from which clinical cancer research may benefit. In this letter, we provide a framework for achieving this progress, including articulation of societal value of trial participation, maximizing design efficiency, and increasing transparency.
A Phase Ib Trial of Personalized Neoantigen Therapy Plus Anti-PD-1 in Patients with Advanced Melanoma, Non-small Cell Lung Cancer, or Bladder Cancer
Highlights • The personalized neoantigen vaccine Neo-PV-01 plus nivolumab is feasible and safe • NEO-PV-01 plus nivolumab stimulates durable neoantigen-specific T cell reactivity • NEO-PV-01-specific T cells have cytotoxic potential and can traffic to the tumor • NEO-PV-01 induces epitope spreading consistent with vaccine-mediated tumor cytotoxicity Summary Neoantigens arise from mutations in cancer cells and are important targets of T cell-mediated anti-tumor immunity.
An umbrella approach to test lung cancer therapies
NEWS AND VIEWS 15 July 2020 A clinical trial has tested the use of gene-sequencing results for lung cancer to match patients to targeted therapies. Some paired treatments were a good fit, but others did not succeed, for reasons that will require further exploration. Alexander Drilon & Alexander Drilon is in the Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, New York 10065, USA, and in the Department of Medicine, Weill Cornell Medical College, New York. Contact Matthew D.
Acquired Resistance to Immune Checkpoint Inhibitors
Abdallah N. Nagasaka M. Abdulfatah E. Shi D. Wozniak A.J. Sukari A. Non-small cell to small cell lung cancer on PD-1 inhibitors: two cases on potential histologic transformation. Lung Cancer (Auckl). 2018; 9: 85-90 Anagnostou V. Smith K.N. Forde P.M. Niknafs N. Bhattacharya R. White J. Zhang T. Adleff V. Phallen J. Wali N. et al. Evolution of neoantigen landscape during immune checkpoint blockade in non-small cell lung cancer. Cancer Discov. 2017; 7: 264-276 Antonia S.J. Borghaei H. Ramalingam S.S. Horn L.
Nivolumab Monotherapy and Nivolumab Plus Ipilimumab in Recurrent Small Cell Lung Cancer: Results From the CheckMate 032 Randomized Cohort
Introduction Patients with recurrent small cell lung cancer (SCLC) have limited treatment options and poor survival.1x1Byers, L.A. and Rudin, C.M. Small cell lung cancer: where do we go from here?. Cancer. 2015; 121: 664–672 Crossref | PubMed | Scopus (176) | Google ScholarSee all References Nivolumab, an anti–programmed death-1 antibody, and ipilimumab, an anti–cytotoxic T-lymphocyte associated protein 4 antibody, are immune checkpoint inhibitors with complementary mechanisms of action.
First-in-human imaging with 89Zr-Df-IAB22M2C anti-CD8 minibody in patients with solid malignancies: preliminary pharmacokinetics, biodistribution, and lesion targeting
Neeta Pandit-Taskar1, Michael Postow1, Matthew Hellmann1, James Harding1, Christopher Barker1, Joseph O'Donoghue1, Martha Ziolkowska1, Shutian Ruan1, Serge Lyashchenko1, Frank Tsai2, Michael Farwell3, Tara Mitchell3, Ron Korn4, William Le5, Jason Lewis1, Wolfgang Weber1, Deepak Behera5, Ian Wilson5, Michael Gordon2, Anna Wu5 and Jedd Wolchok1 1 Memorial Sloan Kettering Cancer Center, United States; 2 Honor Health; 3 University of Pennsylvania; 4 Imaging Endpoints; 5 ImaginAb, Inc.
Treatment Outcomes of Immune-Related Cutaneous Adverse Events
The aim of the current study was to report the efficacy of topical and systemic treatments for immune-related cutaneous adverse events (ircAEs) attributed to checkpoint inhibitors in an uncontrolled cohort of patients referred to oncodermatology clinics. A retrospective analysis of patients with ircAEs evaluated by dermatologists from January 1, 2014, to December 31, 2017, at three tertiary care hospitals and cancer centers were identified through electronic medical records.
Five-Year Overall Survival for Patients With Advanced Non‒Small-Cell Lung Cancer Treated With Pembrolizumab: Results From the Phase I KEYNOTE-001 Study
For patients with non‒small-cell lung cancer (NSCLC), median overall survival (OS) and 5-year survival rates have historically been poor.
Pembrolizumab in patients with advanced non-small-cell lung cancer (KEYNOTE-001): 3-year results from an open-label, phase 1 study
Summary Background The anti-programmed death 1 monoclonal antibody pembrolizumab has shown antitumour activity and is a first-line and second-line treatment option for patients with programmed death ligand 1 (PD-L1)-expressing advanced non-small-cell lung cancer. We report updated 3-year safety and efficacy outcomes from the phase 1 study, KEYNOTE-001.
Tumor Mutational Burden and Efficacy of Nivolumab Monotherapy and in Combination with Ipilimumab in Small-Cell Lung Cancer
Main Text (Cancer Cell 33, 853–861.e1–e4; May 14, 2018) After publication of the original article, authors requested to update potential conflicts of interest that were not initially reported. Their updated potential conflicts of interest are reported here. The complete Declaration of Interests section has now been updated in the article online. The authors would like to apologize for any inconvenience.
Tumor mutational load predicts survival after immunotherapy across multiple cancer types
Abstract Immune checkpoint inhibitor (ICI) treatments benefit some patients with metastatic cancers, but predictive biomarkers are needed. Findings in selected cancer types suggest that tumor mutational burden (TMB) may predict clinical response to ICI. To examine this association more broadly, we analyzed the clinical and genomic data of 1,662 advanced cancer patients treated with ICI, and 5,371 non-ICI-treated patients, whose tumors underwent targeted next-generation sequencing (MSK-IMPACT).
Non-conventional Inhibitory CD4+Foxp3-PD-1hi T Cells as a Biomarker of Immune Checkpoint Blockade Activity
In the originally published version of this article, the Declaration of Interests section only contained a patent related to this work. Although the below additional disclosures are not directly relevant to the published work, the authors put them forward in the spirit of full transparency. The updated Declaration of Interests disclosure, including a list of author interactions with industry, relevant or not relevant to the study, is reported here and in the online version of the paper.
Non-conventional Inhibitory CD4+Foxp3−PD-1hi T Cells as a Biomarker of Immune Checkpoint Blockade Activity
Highlights • CD4 +Foxp3 −PD-1 hi T cells (4PD1 hi) negatively regulate T cell responses • CTLA-4 and PD-1 blockade modulate 4PD1 hi frequency in opposing directions • 4PD1 hi are a pharmacodynamic and negative prognostic factor of checkpoint blockade • Checkpoint blockade regimens may be optimized based on circulating 4PD1 hi levels Summary A significant proportion of cancer patients do not respond to immune checkpoint blockade.
Nivolumab Plus Erlotinib in Patients With EGFR-Mutant Advanced NSCLC
Activating EGFR mutations are found in approximately 15% of adenocarcinomas of the lung in White populations. In Asian populations, EGFR mutations can be identified in 50% or more of adenocarcinomas of the lung.1x1Midha, A., Dearden, S., and McCormack, R. EGFR mutation incidence in non–small-cell lung cancer of adenocarcinoma histology: a systematic review and global map by ethnicity (mutMapII). Am J Cancer Res.
Tumor Mutational Burden and Efficacy of Nivolumab Monotherapy and in Combination with Ipilimumab in Small-Cell Lung Cancer
Durable responses and encouraging survival have been demonstrated with immune checkpoint inhibitors in small-cell lung cancer (SCLC), but predictive markers are unknown. We used whole exome sequencing to evaluate the impact of tumor mutational burden on efficacy of nivolumab monotherapy or combined with ipilimumab in patients with SCLC from the nonrandomized or randomized cohorts of CheckMate 032.
Immunotherapy superior to chemotherapy for advanced lung cancer with high tumor mutational burden
Disclosure: Bristol-Myers Squibb and Ono Pharmaceutical Co. sponsored the study. Hellmann reports paid consultant roles with AstraZeneca, Bristol-Myers Squibb, Genentech/Roche, Janssen, Merck, Mirati Therapeutics, Novartis and Shattuck Labs. He also reports grant/research support from Bristol-Myers Squibb.
Genomic Features of Response to Combination Immunotherapy in Patients with Advanced Non-Small-Cell Lung Cancer
Genomic and Clinical Characteristics of Study Cohort Are Generalizable Tumor Mutation Burden Is Significantly Associated with Improved Efficacy of Combination Immunotherapy Individual Genes and Additional Molecular Features Associated with Response or Resistance to Combination Immunotherapy Tumor Mutation Burden Is Independent of PD-L1 and Remains Significantly Associated with Efficacy in Multivariable Analysis In patients with advanced cancers treated with PD-1 blockade monotherapy, multiple...
Immune-Related Adverse Events Associated with Immune Checkpoint Blockade
This article is available to subscribers. Subscribe now. Already have an account? Sign in Review ArticleFree Preview List of authors. Michael A. Postow, M.D., Robert Sidlow, M.D., and Matthew D. Hellmann, M.D. Related Articles The wide range of immune-related adverse effects associated with immune checkpoint blockade can complicate this effective therapy and limit its use in patients with cancer. This review surveys the adverse effects and their management.
Making It Personal: Neoantigen Vaccines in Metastatic Melanoma
To use the Enhanced view of this article, please enable JavaScript on in your browser and refresh the page. PreviewMaking It Personal: Neoantigen Vaccines in Metastatic Melanoma, Alexandra SnyderxAlexandra SnyderSearch for articles by this authorAffiliationsDepartment of Medicine, Memorial Sloan Kettering Cancer Center, 1275 York Ave., New York, NY 10028, USAAdaptive Biotechnologies, 1551 Eastlake Ave.
Nivolumab in Combination With Platinum‐Based Doublet Chemotherapy for First-Line Treatment of Advanced Non-Small-Cell Lung Cancer
Presented in part at the Chicago Multidisciplinary Symposium in Thoracic Oncology, Chicago, IL, October 30–November 1, 2014; 50th Annual Meeting of the American Society of Clinical Oncology Annual Meeting, Chicago, IL, May 30–June 3, 2014; and European Society for Medical Oncology Congress, Madrid, Spain, September 26–September 30, 2014.
Medians and Milestones in Describing the Path to Cancer Cures: Telling “Tails”
The American Medical Association is accredited by the Accreditation Council for Continuing Medical Education to provide continuing medical education for physicians. The AMA designates this journal-based CME activity for a maximum of 1 AMA PRA Category 1 CreditTM per course. Physicians should claim only the credit commensurate with the extent of their participation in the activity.
Mutational landscape determines sensitivity to PD-1 blockade in non-small cell lung cancer
Immune checkpoint inhibitors, which unleash a patient’s own T cells to kill tumors, are revolutionizing cancer treatment. To unravel the genomic determinants of response to this therapy, we used whole-exome sequencing of non–small cell lung cancers treated with pembrolizumab, an antibody targeting programmed cell death-1 (PD-1).
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