[Combined Regimens in Immunotherapy]. / Kombinované rezimy v imunoterapii.

The advent of immunotherapy has changed our concept of how to manage metastatic disease. With the exception of relatively rare tumors, the treatment of metastatic cancer is still considered as palliative, and in systemic treatment immunotherapy is often selected, considering better tolerance. Immunotherapy opens the perspective of a long-term, possibly durable, response, and, in contrast to other approaches to targeted therapy, is active across a spectrum of tumors. Combined regimens that increase the efficacy, given the context, are thus of importance. The most promising results are currently obtained using a combination of ipilimumab and nivolumab for the treatment of metastatic malignant melanoma and metastatic renal cell carcinoma. Toxicity of the treatment can be managed by supportive care, and combination immunotherapy is gradually becoming established as a standard option in the management of these two neoplastic disorders. Moreover, additional trials using a combination of ipilimumab and nivolumab to treat other tumors are underway as well as studies of other combinations, including those that employ antibodies acting on immune checkpoints in combination with other targeted agents or cytotoxic chemotherapy. Other options include combinations with surgical therapy, i.e., adjuvant or neoadjuvant administration of immunotherapy or with radiotherapy based on the abscopal effect of radiation. Thus, although the results of combination immunotherapy are very promising, this strategy is still in its infancy. Thus, only the next generation of clinical trials will be able to determine to what extent these combined regimens can meet the high expectations of medical oncologists and the general public.Key words: immunotherapy - ipilimumab - nivolumab - pembrolizumab The authors declare they have no potential conflicts of interest concerning drugs, products, or services used in the study. The authors declare they have no potential conflicts of interest concerning drugs, products, or services used in the study. The Editorial Board declares that the manuscript met the ICMJE recommendation for biomedical papers.Submitted: 27. 9. 2017Accepted: 3. 10. 2017.

Immunotherapy-Associated Myocarditis.

The influence of checkpoint inhibitors on the balance between activation and inhibition of T-lymphocytes is strong. The development of checkpoint inhibitors has led to treatments for many malignancies but has also facilitated auto-immune disease. These immunotherapeutic agents could exacerbate already present autoimmune disease or could cause new complications in patients with no prior history of autoimmunity. Monoclonal antibodies targeting immune check points, namely anti-CTLA4 or anti-PD-1/PD-L1, are generally well tolerated; however, treatment with these drugs is associated with a variety of adverse events, such as cardiotoxicity, among others. The main mechanism of cardiac damage is lymphocytic myocarditis, which can consequently cause many symptoms of cardiovascular disease - from asymptomatic elevation of cardiac markers, heart failure, and arrhythmias to cardiogenic shock. Other adverse events include pericardium damage or Tako-tsubo cardiomyopathy. The author declares she has no potential conflicts of interest concerning drugs, products, or services used in the study. The Editorial Board declares that the manuscript met the ICMJE recommendation for biomedical papers.