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  1. Article ; Online: Prognosis of Merkel cell carcinoma patients with autoimmune disorders, other types of immune dysfunction, or immunocompetent status: Analysis of 762 patients.

    Park, Song Y / Hippe, Daniel S / Zawacki, Lauren / Bierma, Marika / Bhatia, Shailender / Nghiem, Paul / Zaba, Lisa C / Singh, Namrata

    Journal of the American Academy of Dermatology

    2024  Volume 90, Issue 5, Page(s) 1018–1020

    MeSH term(s) Humans ; Carcinoma, Merkel Cell/diagnosis ; Carcinoma, Merkel Cell/pathology ; Prognosis ; Skin Neoplasms/pathology ; Autoimmune Diseases/complications ; Autoimmune Diseases/diagnosis ; Merkel cell polyomavirus
    Language English
    Publishing date 2024-01-04
    Publishing country United States
    Document type Journal Article
    ZDB-ID 603641-7
    ISSN 1097-6787 ; 0190-9622
    ISSN (online) 1097-6787
    ISSN 0190-9622
    DOI 10.1016/j.jaad.2023.12.039
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  2. Article: Complete resolution of PD-1 refractory, locoregionally advanced Merkel cell carcinoma with talimogene laherparepvec.

    Singh, Neha / McClure, Erin / Doolittle-Amieva, Coley / Parvathaneni, Upendra / Bhatia, Shailender / Moshiri, Ata S

    JAAD case reports

    2023  Volume 36, Page(s) 15–17

    Language English
    Publishing date 2023-02-06
    Publishing country United States
    Document type Journal Article
    ZDB-ID 2834220-3
    ISSN 2352-5126
    ISSN 2352-5126
    DOI 10.1016/j.jdcr.2022.12.025
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  3. Article: Adverse events of immune checkpoint therapy alone versus when combined with vascular endothelial growth factor inhibitors: a pooled meta-analysis of 1735 patients.

    Kovalenko, Iuliia / Lynn Ng, Wern / Geng, Yimin / Wang, Yinghong / Msaouel, Pavlos / Bhatia, Shailender / Grivas, Petros / Benkhadra, Raed / Alhalabi, Omar

    Frontiers in oncology

    2024  Volume 13, Page(s) 1238517

    Abstract: Background: Combining immune checkpoint therapy (ICT) and vascular endothelial growth factor inhibitors (VEGFi) may result in increased treatment-related and immune-related adverse events (TRAEs and irAEs) compared to ICT alone. This metanalysis was ... ...

    Abstract Background: Combining immune checkpoint therapy (ICT) and vascular endothelial growth factor inhibitors (VEGFi) may result in increased treatment-related and immune-related adverse events (TRAEs and irAEs) compared to ICT alone. This metanalysis was conducted to identify prospective phase II or III clinical studies that evaluated the toxicity profile of ICT + VEGFi compared to ICT alone.
    Methods: A systematic search was performed across all cancer types and major databases until August 10, 2022, and screening was done by two independent investigators. Inclusion criteria included phase 2 or 3 studies with at least one arm of patients treated with combination therapy and one arm treated with monotherapy. Adverse event data were pooled using a restricted maximum likelihood fixed effects model, and heterogeneity using Cochran's Q (chi-square) test.
    Results: 7 out of 9366 studies met the inclusion criteria, and 808 and 927 patients were treated with ICT monotherapy and a combination of ICT with VEGFi, respectively. Only one study reported irAEs, so the analysis was restricted to TRAEs. The total number of TRAEs was significantly higher in the ICT + VEGFi group (RR:1.49; 95% CI 1.37 -1.62; p=1.5×10-21), and more frequent treatment withdrawals were attributed to TRAEs (RR:3.10; 95% CI 1.12-8.59; p=0.029). The highest TRAE effect size increases noted for rash (RR 6.50; 95% CI 3.76 - 11.25; p=2.1×10-11), hypertension (RR:6.07; 95% CI 3.69-10.00; p=1.3×10-12), hypothyroidism (RR:5.02; 95% CI 3.08 - 8.19; p=8.9×10-11), and diarrhea (RR:4.94; 95% CI 3.21-7.62; p=3.8×10-13). Other significantly more frequent TRAEs included nausea, anemia, anorexia, and proteinuria.
    Conclusion: Combination therapy with ICT and VEGFi carries a higher risk of certain TRAEs, such as rash, hypertension, hypothyroidism, diarrhea, nausea, anorexia, and proteinuria, compared to ICT monotherapy. More granular details on the cause of AEs, particularly irAEs, should be provided in future trials of such regimens.
    Language English
    Publishing date 2024-01-04
    Publishing country Switzerland
    Document type Journal Article ; Review
    ZDB-ID 2649216-7
    ISSN 2234-943X
    ISSN 2234-943X
    DOI 10.3389/fonc.2023.1238517
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  4. Article: Harnessing Natural Killer Cells in Cancer Immunotherapy: A Review of Mechanisms and Novel Therapies.

    St-Pierre, Frederique / Bhatia, Shailender / Chandra, Sunandana

    Cancers

    2021  Volume 13, Issue 8

    Abstract: Natural killer (NK) cells are lymphocytes that are integral to the body's innate immunity, resulting in a rapid immune response to stressed or infected cells in an antigen-independent manner. The innate immune system plays an important role in the ... ...

    Abstract Natural killer (NK) cells are lymphocytes that are integral to the body's innate immunity, resulting in a rapid immune response to stressed or infected cells in an antigen-independent manner. The innate immune system plays an important role in the recognition of tumor-derived stress-related factors and is critical to subsequent adaptive immune responses against tumor antigens. The aim of this review is to discuss mechanisms by which tumor cells evade NK cells and to outline strategies that harness NK cells for cancer immunotherapy. We discuss strategies to relieve the exhausted state of NK cells, recent therapies focused on targeting NK-cell-specific activating and inhibitory receptors, the use of cytokines IL-2 and IL-15 to stimulate autologous or allogeneic NK cells, and ongoing trials exploring the use of genetically modified NK cells and chimeric antigen-receptor-modified NK (CAR-NK) cells.
    Language English
    Publishing date 2021-04-20
    Publishing country Switzerland
    Document type Journal Article ; Review
    ZDB-ID 2527080-1
    ISSN 2072-6694
    ISSN 2072-6694
    DOI 10.3390/cancers13081988
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  5. Article ; Online: Response.

    Bhatia, Shailender / Storer, Barry E / Nghiem, Paul

    Journal of the National Cancer Institute

    2017  Volume 109, Issue 10

    Language English
    Publishing date 2017-07-03
    Publishing country United States
    Document type Journal Article ; Comment
    ZDB-ID 2992-0
    ISSN 1460-2105 ; 0027-8874 ; 0198-0157
    ISSN (online) 1460-2105
    ISSN 0027-8874 ; 0198-0157
    DOI 10.1093/jnci/djx053
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  6. Article ; Online: Disparate clinical activity of PD-1 blockade in melanoma subtypes: Know thy enemy!

    Bhatia, Shailender / Margolin, Kim

    Cancer

    2016  Volume 122, Issue 21, Page(s) 3263–3266

    MeSH term(s) Humans ; Melanoma ; Skin Neoplasms
    Language English
    Publishing date 2016--15
    Publishing country United States
    Document type Editorial ; Comment
    ZDB-ID 1429-1
    ISSN 1097-0142 ; 0008-543X ; 1934-662X
    ISSN (online) 1097-0142
    ISSN 0008-543X ; 1934-662X
    DOI 10.1002/cncr.30260
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  7. Article ; Online: Pembrolizumab and other immune checkpoint inhibitors in locally advanced or metastatic Merkel Cell Carcinoma: safety and efficacy.

    Marchand, Antoine / Kervarrec, Thibault / Bhatia, Shailender / Samimi, Mahtab

    Expert review of anticancer therapy

    2020  Volume 20, Issue 12, Page(s) 1093–1106

    Abstract: Introduction: Merkel Cell Carcinoma (MCC) is a rare aggressive skin cancer, mostly affecting elderly patients. Until recently, patients with advanced disease were treated with cytotoxic chemotherapies despite rapid chemoresistance and high toxicity. As ... ...

    Abstract Introduction: Merkel Cell Carcinoma (MCC) is a rare aggressive skin cancer, mostly affecting elderly patients. Until recently, patients with advanced disease were treated with cytotoxic chemotherapies despite rapid chemoresistance and high toxicity. As with other cancers, immune checkpoint inhibitors (CPI), including pembrolizumab, allow durable responses with a manageable safety profile in these patients.
    Areas covered: This review describes the rationale for using PD-1/PD-L1 inhibitors in MCC, as well as efficacy and safety results from the three open-label trials investigating pembrolizumab or other PD-1/PD-L1 inhibitors in patients with advanced MCC. Real-life experience and predictive pre-treatment biomarkers are discussed to assess which patients are likely to be candidates for such strategies. Ongoing fields of research include the use of CPI in the adjuvant or neoadjuvant setting and combined strategies in refractory patients.
    MeSH term(s) Aged ; Antibodies, Monoclonal, Humanized/administration & dosage ; Antibodies, Monoclonal, Humanized/adverse effects ; Antibodies, Monoclonal, Humanized/pharmacokinetics ; B7-H1 Antigen/antagonists & inhibitors ; Biomarkers, Tumor/metabolism ; Carcinoma, Merkel Cell/drug therapy ; Carcinoma, Merkel Cell/pathology ; Drug Resistance, Neoplasm ; Humans ; Immune Checkpoint Inhibitors/administration & dosage ; Immune Checkpoint Inhibitors/adverse effects ; Immune Checkpoint Inhibitors/pharmacology ; Programmed Cell Death 1 Receptor/antagonists & inhibitors ; Skin Neoplasms/drug therapy ; Skin Neoplasms/pathology
    Chemical Substances Antibodies, Monoclonal, Humanized ; B7-H1 Antigen ; Biomarkers, Tumor ; CD274 protein, human ; Immune Checkpoint Inhibitors ; PDCD1 protein, human ; Programmed Cell Death 1 Receptor ; pembrolizumab (DPT0O3T46P)
    Language English
    Publishing date 2020-11-04
    Publishing country England
    Document type Journal Article ; Review
    ZDB-ID 2112544-2
    ISSN 1744-8328 ; 1473-7140
    ISSN (online) 1744-8328
    ISSN 1473-7140
    DOI 10.1080/14737140.2021.1835477
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    Zs.A 5907: Show issues Location:
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  8. Article ; Online: Advances in Immunotherapy for Metastatic Merkel Cell Carcinoma: A Clinician's Guide.

    Paulson, Kelly G / Bhatia, Shailender

    Journal of the National Comprehensive Cancer Network : JNCCN

    2018  Volume 16, Issue 6, Page(s) 782–790

    Abstract: Merkel cell carcinoma (MCC) is a neuroendocrine skin cancer. The clinical impact of MCC has been increasing due to steadily rising incidence rates. Since 2001, more than 24,000 cases of MCC have been reported to the US National Program of Cancer ... ...

    Abstract Merkel cell carcinoma (MCC) is a neuroendocrine skin cancer. The clinical impact of MCC has been increasing due to steadily rising incidence rates. Since 2001, more than 24,000 cases of MCC have been reported to the US National Program of Cancer Registries database, and in 2018, more than 2,500 incident cases are expected. MCC is highly aggressive, and one-third of patients will either present with or develop metastatic disease. Outcomes in patients with metastatic MCC have historically been poor; median time to progression with cytotoxic chemotherapy is only 3 months. MCC has long been appreciated to be immunogenic, with reports of spontaneous regression and responsiveness to immunotherapy. However, the mechanisms of this immunogenicity have only been understood over the past decade, with approximately 80% of cases in the United States associated with the Merkel cell polyomavirus (MCPyV) and expression of viral antigens (virus-positive [VP] MCC), and the remaining 20% of cases caused by UV radiation-induced damage leading to a high mutational burden and expression of neoantigens (virus-negative [VN] MCC). These insights have led to multiple successful trials of immunotherapies for MCC. PD-1 axis checkpoint inhibitors are now regarded as the preferred frontline systemic therapy in eligible patients (including both VP- and VN-MCC), with impressive frequency, durability, and depth of objective responses, which compare favorably to those of most solid tumors. This article reviews the safety and efficacy data from the key clinical trials of immune checkpoint inhibitors for metastatic MCC, and discusses several issues relevant to the clinical use of these agents. Finally, emerging immunotherapies for MCC, including cellular therapies and adjuvant systemic therapies, are reviewed.
    MeSH term(s) Antineoplastic Agents, Immunological/pharmacology ; Antineoplastic Agents, Immunological/therapeutic use ; Carcinoma, Merkel Cell/immunology ; Carcinoma, Merkel Cell/pathology ; Carcinoma, Merkel Cell/therapy ; Carcinoma, Merkel Cell/virology ; Combined Modality Therapy/methods ; Disease Progression ; Drug Resistance, Neoplasm/immunology ; Humans ; Immunotherapy, Adoptive/methods ; Merkel cell polyomavirus/immunology ; Merkel cell polyomavirus/pathogenicity ; Neoplasm Recurrence, Local/immunology ; Neoplasm Recurrence, Local/pathology ; Neoplasm Recurrence, Local/prevention & control ; Neoplasm Recurrence, Local/virology ; Practice Guidelines as Topic ; Programmed Cell Death 1 Receptor/antagonists & inhibitors ; Programmed Cell Death 1 Receptor/immunology ; Randomized Controlled Trials as Topic ; Skin Neoplasms/immunology ; Skin Neoplasms/pathology ; Skin Neoplasms/therapy ; Skin Neoplasms/virology ; Treatment Outcome
    Chemical Substances Antineoplastic Agents, Immunological ; PDCD1 protein, human ; Programmed Cell Death 1 Receptor
    Language English
    Publishing date 2018-06-11
    Publishing country United States
    Document type Journal Article ; Research Support, N.I.H., Extramural ; Review
    ZDB-ID 2250759-0
    ISSN 1540-1413 ; 1540-1405
    ISSN (online) 1540-1413
    ISSN 1540-1405
    DOI 10.6004/jnccn.2018.7049
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  9. Article ; Online: PD-1 Blockade in Melanoma: A Promising Start, but a Long Way to Go.

    Bhatia, Shailender / Thompson, John A

    JAMA

    2016  Volume 315, Issue 15, Page(s) 1573–1575

    MeSH term(s) Antibodies, Monoclonal, Humanized/therapeutic use ; Antineoplastic Agents/therapeutic use ; Female ; Humans ; Male ; Melanoma/drug therapy ; Skin Neoplasms/drug therapy
    Chemical Substances Antibodies, Monoclonal, Humanized ; Antineoplastic Agents
    Language English
    Publishing date 2016-04-19
    Publishing country United States
    Document type Comment ; Editorial
    ZDB-ID 2958-0
    ISSN 1538-3598 ; 0254-9077 ; 0002-9955 ; 0098-7484
    ISSN (online) 1538-3598
    ISSN 0254-9077 ; 0002-9955 ; 0098-7484
    DOI 10.1001/jama.2016.4012
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  10. Article ; Online: Correction to: Extended duration of treatment using reduced‑frequency dosing of anti‑PD‑1 therapy in patients with advanced melanoma and Merkel cell carcinoma.

    Tachiki, Lisa May Ling / Hippe, Daniel S / Silva, Karly Williams / Hall, Evan Thomas / McCamy, William / Fritzsche, Dane / Perdue, Andrea / Majovski, Julia / Pulliam, Thomas / Goldstein, Daniel A / Veatch, Joshua / Ho, Joel / Nghiem, Paul T / Thompson, John A / Bhatia, Shailender

    Cancer immunology, immunotherapy : CII

    2023  Volume 72, Issue 12, Page(s) 4471

    Language English
    Publishing date 2023-11-18
    Publishing country Germany
    Document type Published Erratum
    ZDB-ID 195342-4
    ISSN 1432-0851 ; 0340-7004
    ISSN (online) 1432-0851
    ISSN 0340-7004
    DOI 10.1007/s00262-023-03575-4
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