Side Effect Management of Immunotherapies

.: PREFACE
ÖN SÖZ
PREFACE
Prof. Dr. Mehmet Ali Nahit ŞENDUR
Ankara Yıldırım Beyazıt Üniversitesi Tıp Fakültesi, Tıbbi Onkoloji BD, Ankara, Türkiye
Article Language: TR
İlk olarak 2011 yılında kanser tedavisi olarak kullanılmaya başlanan 'immün kontrol noktası inhibitörleri (ICI)', kanser hastalarının tedavisinde yeni bir çağ açmışlardır. Bağışıklık sisteminin, kanser hücrelerine etkili bir şekilde saldırmasını sağlayan ICI'nın keşfi ile Japon bilim insanı Tasuku Honjo ve Amerikalı bilim insanı James P. Allison 2018 Nobel Fizyoloji veya Tıp Ödülü'ne layık görüldüler. Bu ajanlar ileri evre veya metastatik malign melanom, küçük hücreli dışı akciğer kanseri (KHDAK), baş ve boyun skuamöz kanserleri, ürotelyal karsinom, gastrik adenokarsinom, özofagus kanseri, DNA oranı bozukluğu olan (MSI-High) olan kanser hastaları, klasik Hodgkin lenfoma, hepatoselüler karsinom ve renal hücreli karsinom gibi birçok solid ve hematolojik kanserlerin tedavisinde kullanıma girmiştir. Kullanım endikasyonları hızla genişlemeye devam etmektedir. Hatta son yıllarda erken evre malign melanom, KHDAK ve renal hücreli kanserin adjuvan tedavisinde de etkinlikleri gösterilmeye başlanmıştır. Yeni ICI ajanlarının ve bunların kombinasyonlarının çalışmaları da devam etmektedir.

İmmün kontrol noktası inhibitörlerinin uzun süreli klinik faydalarına rağmen, ICI kullanımı, sitotoksik kemoterapi gibi diğer sistemik tedavilerden farklı olan etki mekanizması nedeniyle bir dizi yan etki ile ilişkilidir. Yan etkiler birçok organı etkileyebilir ve en yaygın olarak deride görülmekle birlikte gastrointestinal sistem, akciğer, tiroid, adrenal, hipofiz, kas-iskelet sistemi, böbrek, sinir, hematolojik, kardiyovasküler ve oküler sistemlerde de görülmektedir.

Son yıllarda iyice hız kazanan klinik araştırmalar sayesinde genişlemesi beklenen immünoterapi spektrumunda, yan etkileri henüz oluşmadan öngörebilmek ve oluşan yan etkileri daha iyi yönetebilmek için daha ileri risk sınıflandırma modelleri geliştirecek ve toksisiteye yol açan patofizyolojik mekanizmaları da iyi bilmek gerekmektedir. Ek olarak bu yan etkilere erken ve zamanında müdahale etmek hayati önem arz etmektedir. Bu nedenle immünoterapi ilişkili yan etkileri ve tedavisini dermatoloji, hepatoloji, gastroenteroloji, nöroloji, endokrinoloji ve kardiyoloji bölümleri ile beraber multidisipliner bir ekiple yönetmek gerekmektedir.

İmmün kontrol noktası inhibitörlerinin kullanımının sürekli genişlemesi ve dinamik gelişmelerin sürekli ve güncel olması nedeniyle bu kitapta immünoterapi ilişkili yan etkiler ve yönetimi, detaylı bir şekilde multidispliner bir ekip anlayışıyla ele alınmıştır.

Saygı ve sevgilerimle.

Prof. Dr. Mehmet Ali Nahit ŞENDUR
Editör
'Immune check point inhibitors (ICI)', which were first used as cancer treatment in 2011, opened a new era in the treatment of cancer patients. Japanese scientist Tasuku Honjo and American scientist James P. Allison were awarded the 2018 Nobel Prize in Physiology or Medicine for the discovery of ICI, which enable the immune system to effectively attack cancer cells. These agents are approved for advanced or metastatic malignant melanoma, non-small cell lung cancer (NSCLC), head and neck squamous cancers, urothelial carcinoma, gastric adenocarcinoma, esophageal cancer, cancer patients with abnormal DNA ratio (MSI-High), classical Hodgkin lymphoma, hepatocellular carcinoma, renal cell carcinoma and have been used in the treatment of many solid and hematological cancers. Indications for use continue to expand rapidly. In recent years, their efficacy have also been demonstrated in the adjuvant treatment of early-stage malignant melanoma, NSCLC and renal cell cancer. Studies of new ICI agents and their combinations are also ongoing.

Despite the long-term clinical benefits of immune checkpoint inhibitors, the use of ICI is associated with a number of side effects due to its mechanism of action that differs from other systemic therapies such as cytotoxic chemotherapy. Side effects can affect many organ system. Although the most common adverse events are dermatological adverse events, immune-related adverse events are also seen in the gastrointestinal system, lung, thyroid, adrenal, pituitary, musculoskeletal, kidney, nervous, hematological, cardiovascular and ocular systems.

In the immunotherapy spectrum, which is expected to expand thanks to clinical studies that have accelerated in recent years, it is necessary to develop more advanced risk classification models and to know the pathophysiological mechanisms that lead to toxicity in order to predict side effects before they occur and to better manage the occurring side effects. In addition, early and timely intervention to these side effects is vital. For this reason, it is necessary to manage immunotherapy-related side effects and treatment with a multidisciplinary team together with dermatology, hepatology, gastroenterology, neurology, endocrinology and cardiology departments. Due to the continuous expansion of the use of immune checkpoint inhibitors and the continuous and up-to-date dynamic developments, this book of immunotherapy-related side effects and their management has been discussed in detail by a multidisciplinary team.

With my love and respect.

Prof. Dr. Mehmet Ali Nahit ŞENDUR
Editor

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