Der Internist
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Tumor cells always exhibit differences to normal cells. These differences can be recognized by the immune system, enabling the destruction of tumor cells by T cells, as was impressively demonstrated by the success of immune checkpoint inhibition, e.g., in malignant melanoma. ⋯ Nevertheless, all of the efforts made in this respect during the past 30 years have been virtually futile. With current knowledge and technology there is new hope.
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The clinical implementation of immunotherapy has broadened the therapeutic options for recurrent and/or metastatic head and neck squamous cell carcinoma (HNSCC). Until 2016, the only molecularly targeted therapy was epidermal growth factor receptor (EGFR) blockade. However, immune checkpoint inhibition has recently become part of first-line treatment in recurrent and/or metastatic HNSCC. ⋯ For recurrent and/or metastatic HNSCC, the occurrence of systemic effects upon radiochemoimmunotherapy in the clinic is on the rise. Hence, the identification of biomarkers for abscopal effects of radiotherapy and unexpected synergisms between chemotherapy and immunotherapy as well as for pseudoprogression is gaining in importance.
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The term "sickle cell disease" covers a group of genetic blood disorders caused by sickle hemoglobin (HbS) alone or in combination with other variants of the β‑globin locus. Sickle cell disease occurs frequently in sub-Saharan Africa, but is also common in Turkey, Greece, Sicily, the Middle East, India, and the Americas. Polymerization of deoxygenated sickle hemoglobin leads to decreased deformability of red blood cells. ⋯ Complications can vary between the different genotypes and it is important to be aware of the special features of the disease. Hydroxycarbamide has been shown to reduce the morbidity and mortality of patients with sickle cell disease. New drugs and novel treatment approaches such as gene therapy are currently being tested.
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Checkpoint blockade contributes to the immunosuppressive microenvironment in classical Hodgkin lymphoma (cHL) and in particular the interaction of Hodgkin cells and macrophages with T‑cells and natural killer cells via programmed cell death 1 (PD-1) and programmed cell death 1 ligand 1 (PD-L1). ⋯ In 60-70% of patients with chemotherapy-refractory cHL, PD‑1 blockade results in responses. Overall survival is excellent and a small number of patients achieve persistent response. Thus, the use of anti-PD‑1 monoclonal antibodies has become an important treatment approach in relapsed cHL in line with the label. The results of first-line therapy are still preliminary; initial phase II studies using nivolumab in combination with doxorubicin (=adriamycin), vinblastin and dacarbazin (AVD) in early unfavorable or advanced stages showed response rates of up to 90%. Thus, implementing immunomodulatory approaches using PD 1‑blockade have resulted in a significant reduction of chemotherapy. This might represent a paradigm shift in the therapy of cHL.
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Although cutaneous melanoma accounts for only about 4% of all skin cancers (including nonmelanocytic skin cancer), it is responsible for 80% of all deaths caused by skin cancer. The introduction of immune checkpoint inhibitors led to a significant improvement in long-term survival of patients in an advanced stage regardless of BRAF mutation status. In addition to targeted therapy for patients with BRAF-mutated melanoma, immunotherapies are the therapies of choice in advanced stages and, since 2018, also in the adjuvant setting. The effectiveness of combination therapies and sequences of targeted and immunotherapies are currently being tested.