{"id":333852,"date":"2020-07-11T02:00:00","date_gmt":"2020-07-11T00:00:00","guid":{"rendered":"https:\/\/medizinonline.com\/the-latest-developments-in-the-field-of-immunotherapy\/"},"modified":"2020-07-11T02:00:00","modified_gmt":"2020-07-11T00:00:00","slug":"the-latest-developments-in-the-field-of-immunotherapy","status":"publish","type":"post","link":"https:\/\/medizinonline.com\/en\/the-latest-developments-in-the-field-of-immunotherapy\/","title":{"rendered":"The latest developments in the field of immunotherapy"},"content":{"rendered":"

The market approval of checkpoint inhibitors has sustainably improved the options for melanoma treatment. Impressive survival rates have been achieved in long-term studies. Although there are still many open questions, such as the management of side effects, modern immunotherapeutics are among the hopeful candidates for the treatment of black skin cancer.<\/strong><\/p>\n

<\/p>\n

Especially in the treatment of non-resectable metastatic melanoma, immunotherapy now plays an important role alongside targeted therapy (BRAF and MEK inhibitors, among others) [1]. The spectrum of approved immunotherapeutics is continuously expanding. In Switzerland, the following checkpoint inhibitors are currently approved for melanoma treatment [2,3]: Ipiliumumab (Yervoy\u00ae<\/sup>), which belongs to CTLA-4, and the PD1 inhibitors nivolumab (Opdivo\u00ae<\/sup>) and pembrolizumab (Keytruda\u00ae<\/sup>). By counteracting the deactivation of the immune system, checkpoint inhibitors allow immune cells to attack the tumor again.<\/p>\n

High 5-year survival rates in long-term study<\/h2>\n

The results of the CheckMate 067 randomized trial in patients with metastatic melanoma are promising [4]. Study participants were assigned to the following three treatment arms: Combination nivolumab plus ipilimumab or nivolumab treatment alone or ipilimumab monotherapy. In the past, these checkpoint inhibitors resulted in impressive remission rates and long-lasting remission. In this study, this trend was confirmed after 5 years in the cohort receiving the combination of nivolumab plus ipilimumab: A 5-year survival of 52% was achieved. This proportion was 44% in the nivolumab condition and 26% under ipilimumab. Progression-free in the nivolumab\/ipilimumab cohort was 36% of patients after 5 years. The success of these therapies is somewhat overshadowed by their relatively high toxicity – in this study, for example, just over half of the patients in the nivolumab\/ ipilimumab condition also experienced grade 3 and 4 adverse events [4].<\/p>\n

The efficacy of ipilimumab was demonstrated years ago in a study involving nearly 700 patients with advanced black skin cancer [5]. Although the therapeutic results were promising, the proportion of those who did not respond to treatment was about 25% [5]. In particular, there are high hopes for the newer checkpoint inhibitors that target the surface molecule PD-1. Inhibition of the PD-1 pathway also promotes cancer cell targeting but appears to have slightly less dangerous side effects than CTLA-4, and a 2012 study with the PD-1 inhibitor nivolumab was encouraging [6]. About a quarter of patients with advanced skin cancer responded to treatment.<\/p>\n

 <\/p>\n

\"\"<\/p>\n

 <\/p>\n

Management of side effects is a challenge<\/h2>\n

The expansion of indications has been accompanied by an increase in patients with immunotherapy-associated adverse events (“IRAE”) [7]. These are different from chemotherapy-related side effects. Thus, alopecia, vomiting, blood count changes, and infections are rare, but various autoimmune phenomena may occur [7]. Therefore, oncologic patients who exhibit new symptoms of this type should be contacted by their treating oncologist. If necessary, immunotherapy should be paused , and in case of severe and unexpected side effects, a report should be made to the pharmacovigilance center [7]. The severity of IRAE and associated implications for the further course of therapy is assessed using the Common Terminology Criteria for Adverse Events (CTCAE), which classifies IRAE into mild (grades 1-2), moderate (grades 3) and heavy (grade 4) Provides for side effects [8\u201310]. IRAE can lead to various skin lesions resembling classic dermatologic disease patterns (e.g., vasculitis, pemphigus, Stevens-Johnson syndrome) and cause an exacerbation of preexisting autoimmune skin disease. In exacerbations of psoriasis, the problem is that therapy with the anti-interleukin-17 antibody secukinumab, although effective, is probably associated with loss of tumor response [11].<\/p>\n

 <\/p>\n

Literature:<\/p>\n

    \n
  1. Olah J: Update on immunotherapy in metastatic melanoma. Prof. Dr. Judit Olah, Review and Updates, Melanoma, EADV Congress, Madrid, Oct. 11, 2019.<\/li>\n
  2. Swissmedic, www.swissmedic.ch<\/li>\n
  3. Swiss Drug Compendium, https:\/\/compendium.ch<\/li>\n
  4. Larkin JMG, et al: 5-year survival outcomes of the CheckMate 067 phase III trial of nivolumab plus ipilimumab (NIVO1IPI) combination therapy in advanced melanoma, Annals of Oncology 2019; 30: Supplement 5, www.annalsofoncology.org<\/li>\n
  5. Hodi FS, et al: Improved survival with ipilimumab in patients with metastatic melanoma. N Engl J Med 2010; 363(8): 711-723.<\/li>\n
  6. Topalian SL, et al: Safety, activity, and immune correlates of anti-PD-1 antibody in cancer. N Engl J Med 2012; 366(26): 2443-2454.<\/li>\n
  7. Gautschi O, et al: Update 2019: side effects of oncological immunotherapies, Swiss Med Forum 2019; 19(0910): 159-163.<\/li>\n
  8. Haanen JBAG; ESMO Guidelines Committee. Management of toxicities from immunotherapy: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up. Ann Oncol 2017; 28(Suppl4): iv119-iv142.<\/li>\n
  9. Brahmer JR, et al; National Comprehensive Cancer Network. Management of Immune-Related Adverse Events in Patients Treated With Immune Checkpoint Inhibitor Therapy: American Society of Clinical Oncology Clinical Practice Guideline. J Clin Oncol 2018; 36(17): 1714-1768.<\/li>\n
  10. Postow MA, Sidlow R, Hellmann MD: Immune-Related Adverse Events Associated with Immune Checkpoint Blockade. N Engl J Med 2018; 378(2): 158-168.<\/li>\n
  11. Esfahani K, Miller WH Jr: Reversal of Autoimmune Toxicity and Loss of Tumor Response by Interleukin-17 Blockade. N Engl J Med 2017; 376(20): 1989-1991.<\/li>\n<\/ol>\n

     <\/p>\n

    DERMATOLOGY PRACTICE 2020; 30(2): 32<\/em><\/p>\n","protected":false},"excerpt":{"rendered":"

    The market approval of checkpoint inhibitors has sustainably improved the options for melanoma treatment. Impressive survival rates have been achieved in long-term studies. Although there are still many open questions,…<\/p>\n","protected":false},"author":7,"featured_media":96306,"comment_status":"closed","ping_status":"","sticky":false,"template":"","format":"standard","meta":{"_acf_changed":false,"pmpro_default_level":"","cat_1_feature_home_top":false,"cat_2_editor_pick":false,"csco_eyebrow_text":"Melanocytic tumors","footnotes":""},"category":[11340,11508,11370,11548,11503],"tags":[24752,12348,12340],"powerkit_post_featured":[],"class_list":["post-333852","post","type-post","status-publish","format-standard","has-post-thumbnail","category-dermatology-and-venereology","category-education","category-oncology","category-rx-en","category-studies","tag-keytruda-en","tag-melanoma-en","tag-skin-cancer","pmpro-has-access"],"acf":[],"publishpress_future_action":{"enabled":false,"date":"2026-06-30 11:26:56","action":"change-status","newStatus":"draft","terms":[],"taxonomy":"category","extraData":[]},"publishpress_future_workflow_manual_trigger":{"enabledWorkflows":[]},"wpml_current_locale":"en_US","wpml_translations":{"fr_FR":{"locale":"fr_FR","id":333860,"slug":"les-derniers-developpements-dans-le-domaine-de-limmunotherapie","post_title":"Les derniers d\u00e9veloppements dans le domaine de l'immunoth\u00e9rapie","href":"https:\/\/medizinonline.com\/fr\/les-derniers-developpements-dans-le-domaine-de-limmunotherapie\/"},"it_IT":{"locale":"it_IT","id":333869,"slug":"gli-ultimi-sviluppi-nel-campo-dellimmunoterapia","post_title":"Gli ultimi sviluppi nel campo dell'immunoterapia","href":"https:\/\/medizinonline.com\/it\/gli-ultimi-sviluppi-nel-campo-dellimmunoterapia\/"},"pt_PT":{"locale":"pt_PT","id":333877,"slug":"os-ultimos-desenvolvimentos-no-dominio-da-imunoterapia","post_title":"Os \u00faltimos desenvolvimentos no dom\u00ednio da imunoterapia","href":"https:\/\/medizinonline.com\/pt-pt\/os-ultimos-desenvolvimentos-no-dominio-da-imunoterapia\/"},"es_ES":{"locale":"es_ES","id":333879,"slug":"los-ultimos-avances-en-el-campo-de-la-inmunoterapia","post_title":"Los \u00faltimos avances en el campo de la inmunoterapia","href":"https:\/\/medizinonline.com\/es\/los-ultimos-avances-en-el-campo-de-la-inmunoterapia\/"}},"_links":{"self":[{"href":"https:\/\/medizinonline.com\/en\/wp-json\/wp\/v2\/posts\/333852","targetHints":{"allow":["GET"]}}],"collection":[{"href":"https:\/\/medizinonline.com\/en\/wp-json\/wp\/v2\/posts"}],"about":[{"href":"https:\/\/medizinonline.com\/en\/wp-json\/wp\/v2\/types\/post"}],"author":[{"embeddable":true,"href":"https:\/\/medizinonline.com\/en\/wp-json\/wp\/v2\/users\/7"}],"replies":[{"embeddable":true,"href":"https:\/\/medizinonline.com\/en\/wp-json\/wp\/v2\/comments?post=333852"}],"version-history":[{"count":0,"href":"https:\/\/medizinonline.com\/en\/wp-json\/wp\/v2\/posts\/333852\/revisions"}],"wp:featuredmedia":[{"embeddable":true,"href":"https:\/\/medizinonline.com\/en\/wp-json\/wp\/v2\/media\/96306"}],"wp:attachment":[{"href":"https:\/\/medizinonline.com\/en\/wp-json\/wp\/v2\/media?parent=333852"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"https:\/\/medizinonline.com\/en\/wp-json\/wp\/v2\/category?post=333852"},{"taxonomy":"post_tag","embeddable":true,"href":"https:\/\/medizinonline.com\/en\/wp-json\/wp\/v2\/tags?post=333852"},{"taxonomy":"powerkit_post_featured","embeddable":true,"href":"https:\/\/medizinonline.com\/en\/wp-json\/wp\/v2\/powerkit_post_featured?post=333852"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}