AB058. Rebound thymic hyperplasia and immune related adverse events: reality or fantasy—a case report
Abstract

AB058. Rebound thymic hyperplasia and immune related adverse events: reality or fantasy—a case report

Bianca Arianna Facchini1, Francesca Sparano1, Angelo Luciano2, Marco Ferrari3, Marianna Tortora2, Erica Pietroluongo2, Lucia Festino1, Claudia Trojaniello1, Vito Vanella1, Maria Grazia Vitale1, Domenico Mallardo1, Miriam Paone1, Mario Giuliano2, Alberto Servetto2, Ester Simeone1, Giovannella Palmieri4, Paolo Antonio Ascierto1, Margaret Ottaviano1

1Unit of Melanoma, Cancer Immunotherapy and Development Therapeutics, Istituto Nazionale Tumori IRCCS (Istituto di Ricovero e Cura a Carattere Scientifico) Fondazione G. Pascale, Naples, Italy; 2Department of Clinical Medicine and Surgery, University of Naples Federico II, Naples, Italy; 3Azienda Ospedaliero Universitaria Pisana, Medical Oncology Unit, Pisa, Italy; 4Regional Coordinating Center for Rare Tumors (CRCTR) of Campania Region at University Federico II, Naples, Italy

Correspondence to: Margaret Ottaviano, MD, PhD. Unit of Melanoma, Cancer Immunotherapy and Development Therapeutics, Istituto Nazionale Tumori IRCCS (Istituto di Ricovero e Cura a Carattere Scientifico) Fondazione G. Pascale, Via Mariano Semmola, Naples 80131, Italy. Email: Margaret.ottaviano@istitutotumori.na.it.

Background: Immune checkpoint inhibitors (ICIs) have dramatically improved the prognosis of metastatic cancer patients. Along with observed durable responses, a considerable rate of immune related adverse events (ir-AEs) is often registered, particularly with the combination of anti-programmed cell death 1 (PD-1) and anti-CTLA-4, probably caused by the loss of immune tolerance under the effects of these ICIs. Considering the key role of the thymus in the development of immune tolerance, it is legit to hypothesize that a possible correlation between the rebound thymic hyperplasia during ICIs and the onset of some ir-AEs may exist.

Case Description: The first patient is a 42-year-old woman with programmed death-ligand 1 (PD-L1) negative metastatic melanoma, who developed, after 2 cycles of nivolumab plus ipilimumab, a persistent fever, shortly followed by grade 4 (CTCAE v. 5.0) ir-hepatitis treated with high dose steroids. During steroids tapering, grade 2 ir-histologically confirmed colitis manifested. After adequate immune suppressive treatment all the ir-AEs resolved and computed tomography (CT) scan showed radiological complete response (CR), persistent so far. The second patient, a 25-year-old man, was also diagnosed with PD-L1 negative metastatic melanoma. As the previous case, after 2 cycles of Nivolumab plus Ipilimumab a persistent fever occurred, followed by grade 4 ir-hepatitis. During the steroids tapering, grade 4 colitis occurred and treatment with anti-TNF-alfa was promptly administered. The subsequent CT scan showed CR. The third patient, a 17-year-old man, was diagnosed with stage IIIB spitzoid melanoma. After 7 cycles of adjuvant anti-programmed cell death 1 (PD-1), he presented grade 2 ir-hepatitis, followed by grade 3 diarrhea. After immune suppressive treatment with steroids, all ir-AEs resolved, however after 3 years from the last dose a histologically ir-hepatitis was again diagnosed. All the CT scans did not show signs of disease recurrence so far.

Conclusions: At the basal CT scan, all the patients presented a thymic hyperplasia, that underwent a radiological evident rebound after ir-AE development. They all manifested similar multiple toxicities managed with immunosuppressive treatments; nevertheless, brilliant responses to treatment were reported. The relation between thymic hyperplasia and ir-AEs onset is still unclear, but taking into account its crucial role in the development of immune tolerance it definitely deserves to be deepened.

Keywords: Thymic hyperplasia; immunotherapy; adverse events; case report

Acknowledgments

Funding: None.

Footnote

Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://med.amegroups.com/article/view/10.21037/med-24-ab058/coif). M.G. reports payment or honoraria from Lilly, Celgene, Novartis, Pfizer, and support for attending meeting or travel from Lilly, Celgene, Novartis, Pfizer, Istituto Gentili, Eisai Europe Ltd., Roche. A.S. reports payment or honoraria from Lilly, Gilead, MSD, Roche, Novartis, MSD, Janssen, AstraZeneca, support for attending meeting or travel from Bristol-Myers Squibb, AstraZeneca, Janssen, and Daiichi Sankyo, and participation on Data Safety Monitoring Boards for MSD and Novartis. E.S. reports financial support from BMS, MSD. P.A.A. reports consulting fees from Bristol-Meyers Squibb, Roche-Genentech, Merck Sharp & Dohme, Novartis, Merck Serono, Pierre-Fabre, AstraZeneca, Sun Pharma, Sanofi, Sandoz, Immunocore, Italfarmaco, Nektar, Boehringer-Ingelheim, Eisai, Regeneron, Daiichi Sankyo, Pfizer, OncoSec, Nouscom, Lunaphore, Seagen, iTeos, Medicenna, Bio-Al Health, ValoTx, Replimmune, Bayer, Erasca, Philogen, Biontech, Anaveon, and support for attending meeting or travel from Pfizer, Bio-Al Health, Replimmune, MSD, Pierre Fabre. P.A.A. also serves as President of Fondazione Melanoma Onlus, Napoli, Italy, President of Campania Society of Immuno Therapy of Cancer (SCITO), Italy, member of Steering Committee of Society of Melanoma Research (SMR) and member of Board of Directors for the Society of Immuno-Therapy of Cancer (SITC). M.O. reports payment or honoraria from MSD, Regeneron, BMS, Novartis, and support for attending meeting or travel from Novartis, MSD, Pierre Fabre, Sun Pharma. The other authors have no conflicts of interest to declare.

Ethical Statement: The authors are accountable for all aspects of the work in ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved. All procedures performed in this study were in accordance with the ethical standards of the institutional and/or national research committee(s) and with the Helsinki Declaration (as revised in 2013). Written informed consent was obtained from the patients for the publication of this case report and accompanying images. A copy of the written consent is available for review by the editorial office of this journal.

Open Access Statement: This is an Open Access article distributed in accordance with the Creative Commons Attribution-NonCommercial-NoDerivs 4.0 International License (CC BY-NC-ND 4.0), which permits the non-commercial replication and distribution of the article with the strict proviso that no changes or edits are made and the original work is properly cited (including links to both the formal publication through the relevant DOI and the license). See: https://creativecommons.org/licenses/by-nc-nd/4.0/.

doi: 10.21037/med-24-ab058
Cite this abstract as: Facchini BA, Sparano F, Luciano A, Ferrari M, Tortora M, Pietroluongo E, Festino L, Trojaniello C, Vanella V, Vitale MG, Mallardo D, Paone M, Giuliano M, Servetto A, Simeone E, Palmieri G, Ascierto PA, Ottaviano M. AB058. Rebound thymic hyperplasia and immune related adverse events: reality or fantasy—a case report. Mediastinum 2024;8:AB058.

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