tumorsMalignant tumoursMalignant tumours2224-50572587-6813Rosoncoweb10.18027/2224-5057-2016-4-68-76tumors-274Research ArticleОРИГИНАЛЬНЫЕ ИССЛЕДОВАНИЯORIGINAL REPORTSИММУНООПОСРЕДОВАННЫЕ НЕЖЕЛАТЕЛЬНЫЕ ЯВЛЕНИЯ, СВЯЗАННЫЕ С ЛЕЧЕНИЕМ ПРЕПАРАТАМИ, БЛОКИРУЮЩИМИ КОНТРОЛЬНЫЕ ТОЧКИ Т-ЛИМФОЦИТОВIMMUNE-MEDIATED ADVERSE EVENTS ASSOCIATED WITH IMMUNE CHECKPOINT INHIBITORS THERAPYРеутоваЕ. В.ReutovaE. V.

Реутова Елена Валерьевна – кандидат медицинских наук, старший научный сотрудник, Москва

Reutova Elena Valeryevna – MD, PhD, senior staff scientist, Moscow

evreutova@rambler.ruЛактионовК. П.LaktionovK. P.

Лактионов Константин Павлович – доктор медицинских наук, профессор, ведущий  научный сотрудник, Москва

Laktionov Konstantin Pavlovich – MD, PhD, DSc, Professor, leading researcher, Moscow

Laktionov.K@mail.ruБредерВ. В.BrederV. V.vbreder@yandex.ruСаранцеваК. А.SarantsevaK. A.sarantsevaka@gmail.comОкружноваМ. А.OkruzhnovaM. A.okruzhnovama@mail.ruПерегудоваМ. В.PeregudovaM. V.m_cherkasova@mail.ruРоссийский онкологический научный центр имени Н. Н. БлохинаРоссияN. N. Blokhin Russian Cancer Research CenterRussian Federation201616112016046876Copyright © Реутова Е.В., Лактионов К.П., Бредер В.В., Саранцева К.А., Окружнова М.А., Перегудова М.В., 20162016Реутова Е.В., Лактионов К.П., Бредер В.В., Саранцева К.А., Окружнова М.А., Перегудова М.В.Reutova E.V., Laktionov K.P., Breder V.V., Sarantseva K.A., Okruzhnova M.A., Peregudova M.V.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/274

В последние годы основной акцент в лекарственном лечении злокачественных опухолей делается на иммунотерапию.

Это обусловлено разработкой и регистрацией нового класса препаратов – блокаторов контрольных точек иммунного пути. Основанием для регистрации этого класса препаратов послужили результаты рандомизированных клинических исследований, показавших преимущество этих препаратов по сравнению со стандартной терапией в общей выживаемости [1–3]. Более благоприятным оказался их токсический профиль. Однако те осложнения, с которыми пришлось столкнуться клиницистам, имели принципиально новый, отличный от обусловленных стандартными цитостатиками характер. Многообразие побочных иммуноопосредованных реакций компенсируется стандартным алгоритмом их коррекции [4]. Раннее выявление и своевременное лечение необходимо для успешного купирования этих осложнений.

In recent years, immunotherapy is the main emphasis approach for malignant tumors treatment due to the development and registration of a new class of drugs –immune checkpoint inhibitors. Results of the randomized clinical trials, which showed a benefit in overall survival in comparison with standard therapy, was the basis for registration of this class of medicines [1–3]. Their toxicity profile is more favorable. However, the adverse reactions, which accrues during immunotherapy, are essentially new and different from standard chemotherapy. The standard management algorithm compensates the variety of immunemediated adverse reactions [4]. Early detection and timely treatment is necessary for the successful management of these adverse reactions. 

иммунотерапияингибиторы контрольных точекиммуноопосредованные нежелательные явленияimmunotherapyimmune checkpoint inhibitorsimmune-mediated adverse eventsReferencesBrahmer J., Reckamp K. L., Baas P. et al. Nivolumab versus Docetaxel in Advanced Squamous-Cell Non-Small-Cell Lung Cancer. N Engl J Med. 2015; 373(2): 123–35.Brahmer J., Reckamp K. L., Baas P. et al. Nivolumab versus Docetaxel in Advanced Squamous-Cell Non-Small-Cell Lung Cancer. N Engl J Med. 2015; 373(2): 123–35.Borghaei H., Paz-Ares L., Horn L. et al. Nivolumab versus Docetaxel in Advanced Nonsquamous Non-Small-Cell Lung Cancer. N Engl J Med. 2015; 373(17): 1627–39.Borghaei H., Paz-Ares L., Horn L. et al. Nivolumab versus Docetaxel in Advanced Nonsquamous Non-Small-Cell Lung Cancer. N Engl J Med. 2015; 373(17): 1627–39.Herbst R. S., Baas P., Kim D. W. et al. Pembrolizumab versus docetaxel for previously treated, PD-L1-positive, advanced non-small-cell lung cancer (KEYNOTE-010): a randomized controlled trial. Lancet. 2016; 387(10027): 1540–50.Herbst R. S., Baas P., Kim D. W. et al. Pembrolizumab versus docetaxel for previously treated, PD-L1-positive, advanced non-small-cell lung cancer (KEYNOTE-010): a randomized controlled trial. Lancet. 2016; 387(10027): 1540–50.Naidoo J., Page D. B., Li B. T. et al. Toxicities of the anti-PD-1 and anti-PD-L1 immune checkpoint antibodies. Ann Oncol. 2015 Dec;26(12):2375–91.Naidoo J., Page D. B., Li B. T. et al. Toxicities of the anti-PD-1 and anti-PD-L1 immune checkpoint antibodies. Ann Oncol. 2015 Dec;26(12):2375–91.Pardoll D. M. The blockade of immune checkpoints in cancer immunotherapy. Nat Rev Cancer. 2012 Mar 22; 12(4):252–64.Pardoll D. M. The blockade of immune checkpoints in cancer immunotherapy. Nat Rev Cancer. 2012 Mar 22; 12(4):252–64.Sarantseva K. A., Laktionava L. V., Reutova E. V., Chernenko P. A., Breder V. V. Immunology: immune response as leading protectionfactor against cancer. Malignant Tumours 2016; 2: 5–14.Sarantseva K. A., Laktionava L. V., Reutova E. V., Chernenko P. A., Breder V. V. Immunology: immune response as leading protectionfactor against cancer. Malignant Tumours 2016; 2: 5–14.Tarhini A. Immune-mediated adverse events associated with ipilimumab ctla-4 blockade therapy: the underlying mechanisms and clinical management. Scientifica (Cairo). 2013; 2013:857519.Tarhini A. Immune-mediated adverse events associated with ipilimumab ctla-4 blockade therapy: the underlying mechanisms and clinical management. Scientifica (Cairo). 2013; 2013:857519.Horvat T. Z., Adel N. G., Dang T. O. et al. Immune-related adverse events, need for systemic immunosuppression, and effects on survival and time to treatment failure in patients with melanoma treated with ipilimumab at memorial sloan kettering cancer center. J Clin Oncol 2015; 33(28): 3193–8.Horvat T. Z., Adel N. G., Dang T. O. et al. Immune-related adverse events, need for systemic immunosuppression, and effects on survival and time to treatment failure in patients with melanoma treated with ipilimumab at memorial sloan kettering cancer center. J Clin Oncol 2015; 33(28): 3193–8.Hodi F. S., O’Day S.J., McDermott D.F. et al. Improved survival with ipilimumab in patients with metastatic melanoma. N Engl J Med 2010; 363: 711e23.Hodi F. S., O’Day S.J., McDermott D.F. et al. Improved survival with ipilimumab in patients with metastatic melanoma. N Engl J Med 2010; 363: 711e23.Topalian S. L., Hodi F. S., Brahmer J. R., Gettinger S. N. et al. Safety, activity, and immune correlates of anti-PD-1 antibody in cancer. N Engl J Med 2012; 366: 2443e54.Topalian S. L., Hodi F. S., Brahmer J. R., Gettinger S. N. et al. Safety, activity, and immune correlates of anti-PD-1 antibody in cancer. N Engl J Med 2012; 366: 2443e54.Michot J. M., Bigenwald C., Champiat S. et al. Immunerelated adverse events with immune checkpoint blockade: a comprehensive review. Eur J Cancer. 2016 Feb;54:1 39–48.Michot J. M., Bigenwald C., Champiat S. et al. Immunerelated adverse events with immune checkpoint blockade: a comprehensive review. Eur J Cancer. 2016 Feb;54:1 39–48.Good-Jacobson K.L., Szumilas C. G., Chen L. et al. PD-1 regulates germinal center B cell survival and the formation and affinity of long-lived plasma cells. Nat Immunol 2010; 11: 535–542.Good-Jacobson K.L., Szumilas C. G., Chen L. et al. PD-1 regulates germinal center B cell survival and the formation and affinity of long-lived plasma cells. Nat Immunol 2010; 11: 535–542.Teply B. A., Lipson E. J. Identification and management of toxicities from immune checkpoint-blocking drugs. Oncology (Williston Park). 2014 Nov;28 Suppl 3:30–8.Teply B. A., Lipson E. J. Identification and management of toxicities from immune checkpoint-blocking drugs. Oncology (Williston Park). 2014 Nov;28 Suppl 3:30–8.O Day S.J., Maio M., Chiarion-Sileni V. et al. Efficacy and safety of ipilimumab monotherapy in patients with pretreated advanced melanoma: a multicentre single-arm phase II study. Ann. Oncol 2010; 21(8):1712–1717 2.O Day S.J., Maio M., Chiarion-Sileni V. et al. Efficacy and safety of ipilimumab monotherapy in patients with pretreated advanced melanoma: a multicentre single-arm phase II study. Ann. Oncol 2010; 21(8):1712–1717 2.Robert C., Ribas A., Wolchok J. D. et al. Anti-programmeddeath-receptor-1 treatment with pembrolizumab in ipilimumab-refractory advanced melanoma: a randomised dose-comparison cohort of a phase 1 trial. Lancet 2014; 384(9948): 1109–1117.Robert C., Ribas A., Wolchok J. D. et al. Anti-programmeddeath-receptor-1 treatment with pembrolizumab in ipilimumab-refractory advanced melanoma: a randomised dose-comparison cohort of a phase 1 trial. Lancet 2014; 384(9948): 1109–1117.European Medicines Agency: EMEA/H/C/002213-PSUSA/00009200/201409 – ipilimumab Product information19/06/2015 Yervoy. http://www.ema.europa.eu/docs/en_GB/document_library/ERAP_-_Product information/human002213/WC500109299.pdf (8 November 2015, data last accessed), August 2015.European Medicines Agency: EMEA/H/C/002213-PSUSA/00009200/201409 – ipilimumab Product information19/06/2015 Yervoy. http://www.ema.europa.eu/docs/en_GB/document_library/ERAP_-_Product information/human002213/WC500109299.pdf (8 November 2015, data last accessed), August 2015.Weber J. S., Antonia S. J., Topalian S. L. et al. Safety profile of nivolumab (NIVO) in patients with advanced melanoma (MEL): a pooled analysis. J Clin Oncol 2015; 33 (suppl).Weber J. S., Antonia S. J., Topalian S. L. et al. Safety profile of nivolumab (NIVO) in patients with advanced melanoma (MEL): a pooled analysis. J Clin Oncol 2015; 33 (suppl).Kyi C., Hellmann M. D., Wolchok J. D. Opportunistic infections in patients treated with immunotherapy for cancer. J Immunother Cancer 2014; 2(1):19.Kyi C., Hellmann M. D., Wolchok J. D. Opportunistic infections in patients treated with immunotherapy for cancer. J Immunother Cancer 2014; 2(1):19.Robert C., Long G. V., Brady B. et al. Nivolumab in previously untreated melanoma without BRAF mutation. N Engl J Med 2015 Jan 22; 372(4).Robert C., Long G. V., Brady B. et al. Nivolumab in previously untreated melanoma without BRAF mutation. N Engl J Med 2015 Jan 22; 372(4).Wolchok J. D., Neyns B., Linette G. et al. Ipilimumab monotherapy in patients with pretreated advanced melanoma: a randomised, double-blind, multicentre, phase 2, doseranging study. Lancet Oncol 2010 Feb; 11(2):155e64.Wolchok J. D., Neyns B., Linette G. et al. Ipilimumab monotherapy in patients with pretreated advanced melanoma: a randomised, double-blind, multicentre, phase 2, doseranging study. Lancet Oncol 2010 Feb; 11(2):155e64.Hofmann L., Forschner A., Loquai C. et al. Cutaneous, gastrointestinal, hepatic, endocrine, and renal side-effects of anti-PD-1 therapy. Eur J Cancer. 2016 Jun; 60: 190–209.Hofmann L., Forschner A., Loquai C. et al. Cutaneous, gastrointestinal, hepatic, endocrine, and renal side-effects of anti-PD-1 therapy. Eur J Cancer. 2016 Jun; 60: 190–209.Belum V. R., Benhuri B., Postow M. A. et al. Characterisation and management of dermatologic adverse events to agents targeting the PD-1 receptor. Eur J Cancer. 2016 Jun; 60: 12–25.Belum V. R., Benhuri B., Postow M. A. et al. Characterisation and management of dermatologic adverse events to agents targeting the PD-1 receptor. Eur J Cancer. 2016 Jun; 60: 12–25.Lacouture M. E., Wolchok J. D., Yosipovitch G. et al. Ipilimumab in patients with cancer and the management of dermatologic adverse events. J Am Acad Drematol. 2014; 71:161–9.Lacouture M. E., Wolchok J. D., Yosipovitch G. et al. Ipilimumab in patients with cancer and the management of dermatologic adverse events. J Am Acad Drematol. 2014; 71:161–9.Langer C. J. Emerging immunotherapies in the treatment of non-small cell lung cancer (NSCLC): The role of immune checkpoint inhibitors. Am. J Clin Oncol.Langer C. J. Emerging immunotherapies in the treatment of non-small cell lung cancer (NSCLC): The role of immune checkpoint inhibitors. Am. J Clin Oncol.Zimmer L., Goldinger S. M., Hofmann L. et al. Neurological, respiratory, musculoskeletal, cardiac and ocular side-effects of anti-PD-1 therapy. Eur J Cancer. 2016 Jun;60:210–25. doi: 10.1016/j.ejca.2016.02.024. Epub 2016 Apr 13.Zimmer L., Goldinger S. M., Hofmann L. et al. Neurological, respiratory, musculoskeletal, cardiac and ocular side-effects of anti-PD-1 therapy. Eur J Cancer. 2016 Jun;60:210–25. doi: 10.1016/j.ejca.2016.02.024. Epub 2016 Apr 13.Wilgenhof S., Neyns B. Anti-CTLA-4 antibody Guillain-Barre syndrome in a melanoma patient. Ann. Oncol.2011; 22: 991–993Wilgenhof S., Neyns B. Anti-CTLA-4 antibody Guillain-Barre syndrome in a melanoma patient. Ann. Oncol.2011; 22: 991–993

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