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  1. Article: Immunotherapy for Management of Thymic Epithelial Tumors: A Double-Edged Sword.

    Ballman, Madison / Zhao, Chen / McAdams, Meredith J / Rajan, Arun

    Cancers

    2022  Volume 14, Issue 9

    Abstract: Thymic epithelial tumors (TETs) are rare thoracic cancers that are broadly classified as thymomas and thymic carcinomas. Surgery is the cornerstone of management for early-stage disease. There are a limited number of effective treatment options for ... ...

    Abstract Thymic epithelial tumors (TETs) are rare thoracic cancers that are broadly classified as thymomas and thymic carcinomas. Surgery is the cornerstone of management for early-stage disease. There are a limited number of effective treatment options for patients with advanced or recurrent disease. The occurrence of paraneoplastic autoimmune disorders in patients with TETs, especially thymomas, creates significant challenges for the development of immunotherapy, including immune checkpoint inhibitors, as a feasible treatment option. In addition, patients with TETs are at increased risk for the development of immune-mediated toxicity with a predilection for musculoskeletal and neuromuscular adverse events upon treatment with immunotherapy. The identification of biomarkers of response and toxicity is expected to play a key role in harnessing the benefits of immunotherapy for patients with TETs. In this paper we review the biology of TETs and the potential effects on the tolerability of immunotherapy. The results of clinical trials of immune checkpoint inhibitors for the treatment of advanced TETs are described to understand the potential risks and benefits of immunotherapy. We also provide an overview of future avenues for treatment with novel immunotherapeutic modalities and opportunities to develop biomarkers to improve the safety and tolerability of immunomodulatory treatments in patients with TETs.
    Language English
    Publishing date 2022-04-20
    Publishing country Switzerland
    Document type Journal Article ; Review
    ZDB-ID 2527080-1
    ISSN 2072-6694
    ISSN 2072-6694
    DOI 10.3390/cancers14092060
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  2. Article ; Online: Reply to K. Takada et al.

    Ballman, Madison / Mullenix, Cristina / Szabo, Eva / Steinberg, Seth M / Rajan, Arun

    JTO clinical and research reports

    2021  Volume 2, Issue 12, Page(s) 100250

    Language English
    Publishing date 2021-12-18
    Publishing country United States
    Document type Journal Article
    ISSN 2666-3643
    ISSN (online) 2666-3643
    DOI 10.1016/j.jtocrr.2021.100250
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  3. Article ; Online: Anti-Interleukin-23 Autoantibodies in Adult-Onset Immunodeficiency.

    Cheng, Aristine / Kashyap, Anuj / Salvator, Helene / Rosen, Lindsey B / Colby, Devon / Ardeshir-Larijani, Fatemeh / Loehrer, Patrick J / Ding, Li / Lugo Reyes, Saul O / Riminton, Sean / Ballman, Madison / Rocco, Joseph M / Marciano, Beatriz E / Freeman, Alexandra F / Browne, Sarah K / Hsu, Amy P / Zelazny, Adrian / Rajan, Arun / Sereti, Irini /
    Zerbe, Christa S / Lionakis, Michail S / Holland, Steven M

    The New England journal of medicine

    2024  Volume 390, Issue 12, Page(s) 1105–1117

    Abstract: Background: Autoantibodies against interleukin-12 (anti-interleukin-12) are often identified in patients with thymoma, but opportunistic infections develop in only some of these patients. Interleukin-12 (with subunits p40 and p35) shares a common ... ...

    Abstract Background: Autoantibodies against interleukin-12 (anti-interleukin-12) are often identified in patients with thymoma, but opportunistic infections develop in only some of these patients. Interleukin-12 (with subunits p40 and p35) shares a common subunit with interleukin-23 (subunits p40 and p19). In a patient with disseminated
    Methods: Among the patients (most of whom had thymoma) who were known to have anti-interleukin-12, we screened for autoantibodies against interleukin-23 (anti-interleukin-23). To validate the potential role of anti-interleukin-23 with respect to opportunistic infection, we tested a second cohort of patients with thymoma as well as patients without either thymoma or known anti-interleukin-12 who had unusual infections.
    Results: Among 30 patients with anti-interleukin-12 who had severe mycobacterial, bacterial, or fungal infections, 15 (50%) also had autoantibodies that neutralized interleukin-23. The potency of such neutralization was correlated with the severity of these infections. The neutralizing activity of anti-interleukin-12 alone was not associated with infection. In the validation cohort of 91 patients with thymoma, the presence of anti-interleukin-23 was associated with infection status in 74 patients (81%). Overall, neutralizing anti-interleukin-23 was detected in 30 of 116 patients (26%) with thymoma and in 30 of 36 patients (83%) with disseminated, cerebral, or pulmonary infections. Anti-interleukin-23 was present in 6 of 32 patients (19%) with severe intracellular infections and in 2 of 16 patients (12%) with unusual intracranial infections, including
    Conclusions: Among patients with a variety of mycobacterial, bacterial, or fungal infections, the presence of neutralizing anti-interleukin-23 was associated with severe, persistent opportunistic infections. (Funded by the National Institute of Allergy and Infectious Diseases and others.).
    MeSH term(s) Adult ; Humans ; Autoantibodies/immunology ; Immunologic Deficiency Syndromes/immunology ; Interleukin-12/antagonists & inhibitors ; Interleukin-12/immunology ; Interleukin-23/antagonists & inhibitors ; Interleukin-23/immunology ; Mycoses/immunology ; Opportunistic Infections/immunology ; Thymoma/immunology ; Thymus Neoplasms/immunology ; Antibodies, Neutralizing/immunology ; Bacterial Infections/immunology
    Chemical Substances Autoantibodies ; Interleukin-12 (187348-17-0) ; Interleukin-23 ; Antibodies, Neutralizing
    Language English
    Publishing date 2024-03-20
    Publishing country United States
    Document type Journal Article ; Validation Study
    ZDB-ID 207154-x
    ISSN 1533-4406 ; 0028-4793
    ISSN (online) 1533-4406
    ISSN 0028-4793
    DOI 10.1056/NEJMoa2210665
    Database MEDical Literature Analysis and Retrieval System OnLINE

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    In stock of ZB MED Cologne/Königswinter

    Ua VI Zs.34: Show issues Location:
    Je nach Verfügbarkeit (siehe Angabe bei Bestand)
    bis Jg. 2021: Bestellungen von Artikeln über das Online-Bestellformular
    ab Jg. 2022: Lesesaal (EG)

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  4. Article ; Online: Joint-Predominant Rheumatic Complications of Immune Checkpoint Inhibitor Therapy in Patients with Thymic Epithelial Tumors.

    Mullenix, Cristina / Ballman, Madison / Chen, Haobin / Swift, Shannon / McAdams, Meredith J / Tsai, Yo-Ting / Donahue, Renee N / Poretta, Trina / Gupta, Sarthak / Loehrer, Patrick J / Schlom, Jeffrey / Gulley, James L / Rajan, Arun

    The oncologist

    2022  Volume 27, Issue 4, Page(s) e353–e356

    Abstract: Immune checkpoint inhibitors (ICIs) have revolutionized the treatment of advanced cancers. However, activation of the immune system can occasionally cause life-threatening toxicity involving critical organs. Induction of immune-mediated toxicity is a ... ...

    Abstract Immune checkpoint inhibitors (ICIs) have revolutionized the treatment of advanced cancers. However, activation of the immune system can occasionally cause life-threatening toxicity involving critical organs. Induction of immune-mediated toxicity is a significant concern for patients with thymic epithelial tumors (TETs) due to defects in immune tolerance. An increased risk of skeletal and cardiac muscle inflammation following treatment with ICIs is well recognized in patients with advanced TETs. However, uncommon musculoskeletal and rheumatic complications can also occur. The cases presented in this report highlight the spectrum of presentation of immune-mediated, joint-predominant musculoskeletal adverse events in patients with advanced TETs treated with ICIs, including polymyalgia rheumatica-like illness and inflammatory arthritis.
    MeSH term(s) Humans ; Immune Checkpoint Inhibitors ; Immunotherapy/adverse effects ; Myositis/chemically induced ; Neoplasms/drug therapy ; Neoplasms, Glandular and Epithelial/drug therapy ; Polymyalgia Rheumatica/drug therapy ; Polymyalgia Rheumatica/etiology ; Thymus Neoplasms/drug therapy
    Chemical Substances Immune Checkpoint Inhibitors
    Language English
    Publishing date 2022-04-05
    Publishing country England
    Document type Journal Article ; Research Support, N.I.H., Intramural ; Research Support, Non-U.S. Gov't ; Research Support, N.I.H., Extramural
    ZDB-ID 1409038-7
    ISSN 1549-490X ; 1083-7159
    ISSN (online) 1549-490X
    ISSN 1083-7159
    DOI 10.1093/oncolo/oyac026
    Database MEDical Literature Analysis and Retrieval System OnLINE

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    In stock of ZB MED Cologne/Königswinter

    Zs.A 4845: Show issues Location:
    Je nach Verfügbarkeit (siehe Angabe bei Bestand)
    bis Jg. 1994: Bestellungen von Artikeln über das Online-Bestellformular
    Jg. 1995 - 2021: Lesesall (2.OG)
    ab Jg. 2022: Lesesaal (EG)
    Zs.MO 494: Show issues

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  5. Article ; Online: Tolerability of Coronavirus Disease 2019 Vaccines, BNT162b2 and mRNA-1273, in Patients With Thymic Epithelial Tumors.

    Ballman, Madison / Swift, Shannon / Mullenix, Cristina / Mallory, Yvonne / Zhao, Chen / Szabo, Eva / Shelat, Meenakshi / Sansone, Susan / Steinberg, Seth M / McAdams, Meredith J / Rajan, Arun

    JTO clinical and research reports

    2021  Volume 2, Issue 10, Page(s) 100229

    Abstract: Introduction: Defects in immunologic self-tolerance result in an increased risk for development of paraneoplastic autoimmune diseases (ADs) and immune-mediated toxicity in response to immune stimulation in individuals with thymic epithelial tumors (TETs) ...

    Abstract Introduction: Defects in immunologic self-tolerance result in an increased risk for development of paraneoplastic autoimmune diseases (ADs) and immune-mediated toxicity in response to immune stimulation in individuals with thymic epithelial tumors (TETs). We conducted a survey to evaluate the tolerability of coronavirus disease 2019 (COVID-19) mRNA vaccines in patients with TETs, including individuals with preexisting AD.
    Methods: After reviewing published data on adverse events associated with the BNT162b2 (Pfizer, Inc., and BioNTech) and mRNA-1273 (ModernaTX, Inc.) mRNA vaccines, we designed and administered a questionnaire to participants at the following three time points: after each dose of vaccination and 1 month after the final dose. Questions related to AD and use of immunosuppressive drugs were included. Descriptive statistics were used to analyze data, and results were compared with previously described results related to the BNT162b2 and mRNA-1273 vaccines.
    Results: From February 26 to June 1, 2021, we administered the survey to 54 participants (median age = 58 y, thymoma = 33, preexisting AD = 19). Common adverse events included injection site pain, fatigue, and headaches. There were no vaccination-related hospitalizations or deaths. Autoimmune flares occurred in three patients (16%) after the first dose and three patients (17%) after the second dose. Most AD flares were mild and self-limited. One patient (2%) was diagnosed with having a new AD after vaccination.
    Conclusions: Tolerability of COVID-19 mRNA vaccines in patients with TETs is comparable to the general population. Most patients with preexisting AD did not experience disease flares, and the development of new AD was rare. Patients with TETs should be encouraged to get vaccinated against COVID-19 owing to the documented benefits of vaccination and manageable risk profile.
    Language English
    Publishing date 2021-09-08
    Publishing country United States
    Document type Journal Article
    ISSN 2666-3643
    ISSN (online) 2666-3643
    DOI 10.1016/j.jtocrr.2021.100229
    Database MEDical Literature Analysis and Retrieval System OnLINE

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