tumorsMalignant tumoursMalignant tumours2224-50572587-6813Rosoncoweb10.18027/2224-5057-2023-13-1-24-29tumors-1101Research ArticleКЛИНИЧЕСКИЕ СЛУЧАИCLINICAL NOTESКлинический случай: сочетание иммуноопосредованной тромбоцитопении и миокардита на фоне лечения немелкоклеточного рака легкого ингибиторами контрольных точекCase report: combination of immune-related thrombocytopenia and myocarditis in а patient treated with immune checkpoint inhibitors for non‑small cell lung cancerЮгайС. В.YugayS. V.

Сергей В. Югай, врач-онколог

Санкт-Петербург

Sergey V. Yugay, oncologist

Saint Petersburg

ДехановаК. В.DehanovaК. V.

Ксения В. Деханова, клинический ординатор

Москва

Xenia V. Dehanova, clinical resident

Moscow

РыковИ. В.RikovI. V.

Иван В. Рыков, к. м. н., заведующий отделением онкологии; преподаватель кафедры онкологии

Санкт-Петербург

Ivan V. Rikov, MD, PhD, Head of the Oncology DepartmentSaint Petersburg; Lecturer, OncologyDepartment

Saint Petersburg

БаллюзекМ. Ф.BalluzekМ. F.

Марина Ф. Баллюзек, д. м. н., профессор, заместитель главного врача по медицинской части, заведующая отделением кардиологии; профессор кафедры терапии

Санкт-Петербург

Marina F. Balluzek, MD, PhD, DSc, Professor, Deputy Physician-in-Chief for Medicine, Head of the Cardiology Department; Professor of the Therapy Department

Saint Petersburg

ФГБУЗ ВО «Санкт-Петербургская клиническая больница РАН»РоссияSaint Petersburg Clinical HospitalRussian FederationФГБУ «ГНЦ ФМБЦ им. А. И. Бурназяна ФМБА России»РоссияA. I. Burnazyan Federal Medical Biophysical CenterRussian FederationФГБУЗ ВО «Санкт-Петербургская клиническая больница РАН»; Санкт-Петербургский государственный университетРоссияSaint Petersburg Clinical Hospital; Saint Petersburg State UniversityRussian Federation2023070320231312429Copyright © Югай С.В., Деханова К.В., Рыков И.В., Баллюзек М.Ф., 20232023Югай С.В., Деханова К.В., Рыков И.В., Баллюзек М.Ф.Yugay S.V., Dehanova К.V., Rikov I.V., Balluzek М.F.Данная работа распространяется под лицензией Creative Commons Attribution 4.0.This work is licensed under a Creative Commons Attribution 4.0 License.https://www.malignanttumors.org/jour/article/view/1101

Иммуноопосредованные нежелательные явления (иНЯ) являются актуальной проблемой современной онкологии. При лечении пациентов с солидными опухолями ингибиторами контрольных точек (анти-PD-1, анти-CTLA-4, PD-L1) частота иНЯ достигает 60–85 % [1]. Примерно в 40 % случаев иНЯ требуют полной отмены терапии [2]. К наиболее частым осложнениям этого типа относятся эндокринопатии (до 10 %), пульмониты (5–10 %), аутоимунные гепатиты (до 20 %), колиты (до 30 %), кожная токсичность (до 50 %) [3]. Другие формы нежелательных явлений, такие как гематологическая и кардиоваскулярная токсичность, встречаются крайне редко. Мы описываем клинический случай развития двух редких осложнений у пациента, получающего терапию пембролизумабом по поводу распространенной стадии PD-L1‑позитивного немелкоклеточного рака легкого.

Immune-related adverse events (irAE) present a unique challenge in modern oncology. In patient treated with immune checkpoint inhibitors (anti-PD-1, anti-CTLA-4, anti-PD-L1) for solid tumors irAEs rate ranges from 60 to 85 % [1]. irAEs lead to complete treatment discontinuation in approximately 40 % of patients [2]. The most common irAEs are endocrinopathies (up to 10 %), pneumonitis (5 to 10 %), autoimmune hepatitis (up to 20 %), colitis (up to 30 %), and skin toxicity (up to 50 %) [3]. Other forms of adverse events, such as hematologic and cardiovascular toxicities, are very rarely reported. We present a clinical case of two rare adverse events in a patient treated with pembrolizumab for PD-L1‑positive advanced non-small cell lung cancer.

иммуноопосредованные нежелательные явленияPD-L1 ингибиторыфокальный миокардитаутоиммунная тромбоцитопенияМРТ сердцаimmune-related adverse eventsPD-L1 inhibitorsfocal myocarditisautoimmune thrombocytopeniacardiac MRIReferencesHryniewicki, A. T., Wang, C., Shatsky, R. A., & Coyne, C. J. (2018). Management of Immune Checkpoint Inhibitor Toxicities : A Review and Clinical Guideline for Emergency Physicians. Journal of Emergency Medicine, 55 (4), 489–502. https://doi.org/10.1016/j.jemermed.2018.07.005.Hryniewicki, A. T., Wang, C., Shatsky, R. A., & Coyne, C. J. (2018). Management of Immune Checkpoint Inhibitor Toxicities : A Review and Clinical Guideline for Emergency Physicians. Journal of Emergency Medicine, 55 (4), 489–502. https://doi.org/10.1016/j.jemermed.2018.07.005.Haanen, J. B. A. G., Carbonnel, F., Robert, C., Kerr, K. M., Peters, S., Larkin, J., & Jordan, (2017). Management of toxicities from immunotherapy : ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up. Annals of Oncology, 28 (Supplement 4), iv119–iv142. https://doi.org/10.1093/annonc/mdx225.Haanen, J. B. A. G., Carbonnel, F., Robert, C., Kerr, K. M., Peters, S., Larkin, J., & Jordan, (2017). Management of toxicities from immunotherapy : ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up. Annals of Oncology, 28 (Supplement 4), iv119–iv142. https://doi.org/10.1093/annonc/mdx225.Gürdoğan M, Yalta K. Myocarditis associated with immune checkpoint inhibitors : Practical considerations in diagnosis and management. Anatol J Cardiol. 2020 ; 24 (2) : 68–75. doi:10.14744/AnatolJCardiol.2020.Gürdoğan M, Yalta K. Myocarditis associated with immune checkpoint inhibitors : Practical considerations in diagnosis and management. Anatol J Cardiol. 2020 ; 24 (2) : 68–75. doi:10.14744/AnatolJCardiol.2020.Zhang L., Awadalla M., Mahmood S.S., Nohria A., Hassan M.Z.O., Thuny F., et al. Cardiovascular magnetic resonance in immune checkpoint inhibitor-associated myocarditis. Eur Heart J. 2020 ; 41 : 1733–43.Zhang L., Awadalla M., Mahmood S.S., Nohria A., Hassan M.Z.O., Thuny F., et al. Cardiovascular magnetic resonance in immune checkpoint inhibitor-associated myocarditis. Eur Heart J. 2020 ; 41 : 1733–43.Brahmer J.R., Lacchetti C., Schneider B.J., et al. Management of Immune-Related Adverse Events in Patients Treated With Immune Checkpoint Inhibitor Therapy : American Society of Clinical Oncology Clinical Practice Guideline. National Comprehensive Cancer Network. J ClinOncol. 2018 Jun 10 ; 36 (17) : 1714–1768.Brahmer J.R., Lacchetti C., Schneider B.J., et al. Management of Immune-Related Adverse Events in Patients Treated With Immune Checkpoint Inhibitor Therapy : American Society of Clinical Oncology Clinical Practice Guideline. National Comprehensive Cancer Network. J ClinOncol. 2018 Jun 10 ; 36 (17) : 1714–1768.Ahmad, S., Lewis, M., Corrie, P., &Iddawela, M. (2012). Ipilimumab-induced thrombocytopenia in a patient with metastatic melanoma. Journal of Oncology Pharmacy Practice, 18 (2), 287–292. https://doi.org/10.1177/107815521141100.Ahmad, S., Lewis, M., Corrie, P., &Iddawela, M. (2012). Ipilimumab-induced thrombocytopenia in a patient with metastatic melanoma. Journal of Oncology Pharmacy Practice, 18 (2), 287–292. https://doi.org/10.1177/107815521141100.Le Roy, A., Kempf, E., Ackermann, F., Routier, E., Robert, C., Turpin, A., Marabelle, A., Mateus, C., Michot, J. M., &Lambotte, O. (2016). Two cases of immune thrombocytopenia associated with pembrolizumab. European Journal of Cancer, 54 (August 2014), 172–174. https://doi.org/10.1016/j.ejca.2015.10.073.Le Roy, A., Kempf, E., Ackermann, F., Routier, E., Robert, C., Turpin, A., Marabelle, A., Mateus, C., Michot, J. M., &Lambotte, O. (2016). Two cases of immune thrombocytopenia associated with pembrolizumab. European Journal of Cancer, 54 (August 2014), 172–174. https://doi.org/10.1016/j.ejca.2015.10.073.Mouri, A., Kaira, K., Shiono, A., Miura, Y., &Kagamu, H. (2020). Severe Thrombocytopenia Associated with Pembrolizumab in Patients with Non-small Cell Lung Cancer (NSCLC) : A case report and literature review. In Vivo, 34 (2), 877–880. https://doi.org/10.21873/invivo.11852.Mouri, A., Kaira, K., Shiono, A., Miura, Y., &Kagamu, H. (2020). Severe Thrombocytopenia Associated with Pembrolizumab in Patients with Non-small Cell Lung Cancer (NSCLC) : A case report and literature review. In Vivo, 34 (2), 877–880. https://doi.org/10.21873/invivo.11852.Song, P., & Zhang, L. (2019). Eltrombopag treatment for severe refractory thrombocytopenia caused by pembrolizumab. European Journal of Cancer, 121, 4–6. https://doi.org/10.1016/j.ejca.2019.08.003.Song, P., & Zhang, L. (2019). Eltrombopag treatment for severe refractory thrombocytopenia caused by pembrolizumab. European Journal of Cancer, 121, 4–6. https://doi.org/10.1016/j.ejca.2019.08.003.Shiuan, E., Beckermann, K. E., Ozgun, A., Kelly, C., McKean, M., McQuade, J., Thompson, M. A., Puzanov, I., Greer, J. P., Rapisuwon, S., Postow, M., Davies, M. A., Eroglu, Z., & Johnson, D. (2017). Thrombocytopenia in patients with melanoma receiving immune checkpoint inhibitor therapy. Journal for ImmunoTherapy of Cancer, 5 (1), 4–9. https://doi.org/10.1186/s40425-017-0210-0.Shiuan, E., Beckermann, K. E., Ozgun, A., Kelly, C., McKean, M., McQuade, J., Thompson, M. A., Puzanov, I., Greer, J. P., Rapisuwon, S., Postow, M., Davies, M. A., Eroglu, Z., & Johnson, D. (2017). Thrombocytopenia in patients with melanoma receiving immune checkpoint inhibitor therapy. Journal for ImmunoTherapy of Cancer, 5 (1), 4–9. https://doi.org/10.1186/s40425-017-0210-0.Chaturvedi, S., Arnold, D. M., & McCrae, K. R. (2018). Splenectomy for immune thrombocytopenia : Down but not out. Blood, 131 (11), 1172–1182. https://doi.org/10.1182/blood-2017-09-74235311.Chaturvedi, S., Arnold, D. M., & McCrae, K. R. (2018). Splenectomy for immune thrombocytopenia : Down but not out. Blood, 131 (11), 1172–1182. https://doi.org/10.1182/blood-2017-09-74235311.Neunert, C., Lim, W., Crowther, M., Cohen, A., Solberg, L., &Crowther, M. A. (2011). The American Society of Hematology 2011 evidence-based practice guideline for immune thrombocytopenia. Blood, 117 (16), 4190–4207. https://doi.org/10.1182/blood-2010-08-302984.Neunert, C., Lim, W., Crowther, M., Cohen, A., Solberg, L., &Crowther, M. A. (2011). The American Society of Hematology 2011 evidence-based practice guideline for immune thrombocytopenia. Blood, 117 (16), 4190–4207. https://doi.org/10.1182/blood-2010-08-302984.Johnson, D. B., Balko, J. M., Compton, M. L., Chalkias, S., Gorham, J., Xu, Y., Hicks, M., Puzanov, I., Alexander, M. R., Bloomer, T. L., Becker, J. R., Slosky, D. A., Phillips, E. J., Pilkinton, M. A., Craig-Owens, L ., Kola, N., Plautz, G., Reshef, D. S., Deutsch, J. S., Moslehi, J. J. (2016). Fulminant Myocarditis with Combination Immune Checkpoint Blockade. New England Journal of Medicine, 375 (18), 1749–1755. https://doi.org/10.1056/nejmoa1609214.Johnson, D. B., Balko, J. M., Compton, M. L., Chalkias, S., Gorham, J., Xu, Y., Hicks, M., Puzanov, I., Alexander, M. R., Bloomer, T. L., Becker, J. R., Slosky, D. A., Phillips, E. J., Pilkinton, M. A., Craig-Owens, L ., Kola, N., Plautz, G., Reshef, D. S., Deutsch, J. S., Moslehi, J. J. (2016). Fulminant Myocarditis with Combination Immune Checkpoint Blockade. New England Journal of Medicine, 375 (18), 1749–1755. https://doi.org/10.1056/nejmoa1609214.Tawbi, H. A., Forsyth, P. A., Algazi, A., Hamid, O., Hodi, F. S., Moschos, S. J., Khushalani, N. I., Lewis, K., Lao, C. D., Postow, M. A., Atkins, M. B., Ernstoff, M. S., Reardon, D. A., Puzanov, I., Kudchadkar, R. R., Thomas, R. P., Tarhini, A., Pavlick, A. C., Jiang, J., Margolin, K. (2018). Combined Nivolumab and Ipilimumab in Melanoma Metastatic to the Brain. New Eng J Med, 379 (8), 722–730. https://doi.org/10.1056/nejmoa1805453.Tawbi, H. A., Forsyth, P. A., Algazi, A., Hamid, O., Hodi, F. S., Moschos, S. J., Khushalani, N. I., Lewis, K., Lao, C. D., Postow, M. A., Atkins, M. B., Ernstoff, M. S., Reardon, D. A., Puzanov, I., Kudchadkar, R. R., Thomas, R. P., Tarhini, A., Pavlick, A. C., Jiang, J., Margolin, K. (2018). Combined Nivolumab and Ipilimumab in Melanoma Metastatic to the Brain. New Eng J Med, 379 (8), 722–730. https://doi.org/10.1056/nejmoa1805453.Nghiem, P. T., Bhatia, S., Lipson, E. J., Kudchadkar, R. R., Miller, N. J., Annamalai, L., Berry, S., Chartash, E. K., Daud, A., Fling, S. P., Friedlander, P. A., Kluger, H. M., Kohrt, H. E., Lundgren, L ., Margolin, K., Mitchell, A., Olencki, T., Pardoll, D. M., Reddy, S. A., … Cheever, M. A. (2016). PD-1 Blockade with Pembrolizumab in Advanced Merkel-Cell Carcinoma. New Engl J Med, 374 (26), 2542–2552. https://doi.org/10.1056/nejmoa1603702.Nghiem, P. T., Bhatia, S., Lipson, E. J., Kudchadkar, R. R., Miller, N. J., Annamalai, L., Berry, S., Chartash, E. K., Daud, A., Fling, S. P., Friedlander, P. A., Kluger, H. M., Kohrt, H. E., Lundgren, L ., Margolin, K., Mitchell, A., Olencki, T., Pardoll, D. M., Reddy, S. A., … Cheever, M. A. (2016). PD-1 Blockade with Pembrolizumab in Advanced Merkel-Cell Carcinoma. New Engl J Med, 374 (26), 2542–2552. https://doi.org/10.1056/nejmoa1603702.Zhang L., Awadalla M., Mahmood S.S., Nohria A., Hassan M.Z.O., Thuny F., et al. Cardiovascular magnetic resonance in immune checkpoint inhibitor-associated myocarditis. Eur Heart J. 2020 ; 41 : 1733–43Zhang L., Awadalla M., Mahmood S.S., Nohria A., Hassan M.Z.O., Thuny F., et al. Cardiovascular magnetic resonance in immune checkpoint inhibitor-associated myocarditis. Eur Heart J. 2020 ; 41 : 1733–43

The authors declare that there are no conflicts of interest present.