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SummaryThe biology of non-small cell lung cancer (NSCLC) is driven by a complex mutational landscape, and the detection of driver molecular alterations by next-generation sequencing is key for identification of druggable alterations. Thus, broad molecular profiling displays a standard-of-care approach particularly in patients with advanced adenocarcinoma at the time of the initial diagnosis, but also at the time of acquired resistance to tyrosine kinase inhibitors, guiding further treatment choices. Sequencing of plasma-circulating tumor DNA is of increasing importance in NSCLC diagnostics due to the easy accessibility, representing an optimal tool for longitudinal monitoring of the disease course.

SummaryPrimary pulmonary sarcomas (PPS) are rare mesenchymal lung cancers, which do not present clinically or radiological different to lung carcinomas. Definite PPS diagnosis can only be made by histological analysis and detailed staging examinations in order to exclude a secondary pulmonary malignancy such as metastatic soft tissue sarcoma or another solid tumour. Here we present the case of a 66-year-old woman with a pulmonary mass infiltrating the diaphragm and the mediastinal adipose tissue, which was identified as leiomyosarcoma. The patient received curative surgery with complete tumour R0 resection. The prognosis of PPS is defined by tumour size, lymph node status and histological grading. Surgery is the mainstay of therapy and there is no definitive indication for adjuvant therapy for R0-resected and lymph-node-negative patients like in our case. However, multimodal therapy approaches such as (neo)adjuvant chemo- and radiotherapy can contribute to improving locoregional tumour control, which is the most important prognostic factor. With our case report we want to raise awareness for pulmonary sarcomas as a relevant proportion of rare lung cancers which have to be kept in mind during the differential diagnosis. Moreover, we aim to discuss the complex and individual interdisciplinary management.

SummaryA deeper understanding of disease biology and the advent of targeted drugs have implemented chemotherapy-free treatment options in chronic lymphocytic leukemia (CLL). With consistently superior outcome data and good tolerability, the Bruton’s kinase inhibitor ibrutinib as well as the B‑cell lymphoma 2 inhibitor venetoclax +/− CD20 antibody have recently been licensed for first-line treatment independently of TP53 status and are currently recommended as therapy of choice in most patient subgroups according to international management guidelines. Survival curves, however, have not reached a plateau and relapse due to acquired resistance or drug intolerance remain major hurdles in CLL treatment. Clinical trials currently focus on the most promising combinations and sequences of highly effective targeted drugs aimed at avoiding drug resistance by further enhancing eradication of minimal residual disease and optimizing drug tolerability. This brief review provides an update on the recently presented clinical trial data in first-line CLL at ASH 2019 and discusses clinically relevant obstacles to overcome.

SummaryChimeric antigen receptor T cells (CAR-T cells) are a novel form of cellular immunotherapy for patients with hematologic and oncologic malignancies. Known side effects of these approved cellular immunotherapies are cytokine release syndrome, immune-cell associated neurotoxicity syndrome, cytopenias, infections and long-lasting B cell aplasia. Safe administration of CAR-T cell therapy requires thorough patient selection and patient care in qualified CAR-T cell centers.

SummaryThe treatment options for newly diagnosed and relapsed/refractory acute myeloid leukemia (AML) have substantially improved over the last 5 years. However, even though novel targeted agents (e.g. venetoclax, IDH1/2 and novel FLT-3 inhibitors; cytosolic isocitrate dehydrogenase 1/2 and fms-like tyrosine kinase 3 inhibitor) and improved chemotherapeutics (e.g. CPX-351; liposomale Daunorubicin/Cytarabine) are entering clinics, physicians are still confronted with high relapse and treatment failure rates. Thus, novel new strategies are required to improve AML therapy. Application of genetically engineered T cells (i.e. chimeric antigen receptor T cells, CAR-T cells) has proven to be highly effective in B cell-derived neoplasia and early data suggest also a high potential in the treatment of AML. This short review highlights the current approaches but also limitations of CAR-T cell therapy in AML precluding their current routine clinical use. Among a plethora of problems to be overcome, a critical issue will be to find relatively selective actionable targets in AML.

Chronic myeloid leukaemia (CML) is a paradigmatic disease, as knowledge on the molecular pathology of CML has driven the development of targeted drugs, which finally led to a substantial improvement of the patients' prognosis. However, despite very potent drugs, such as Imatinib, Nilotinib and Dasatinib for first- and second-line therapy are available, there is still place for improvement. Especially, selection of highly resistant T315I mutated clones represents a relevant clinical problem. The highlight of the 52nd Annual Meeting of the American Society (ASH) in 2010 for CML patients was data marking a profound step forward for patients developing a T315I mutation by providing safety and first efficacy results from a clinical trial testing Ponatinib, a TKI targeting T315I-mutated CML. These very early results from a small patient cohort provide a rationale basis for prospective testing of the drug in T315I-mutated CML and will help to further complement the "TKI cocktail" now available for CML patients.

Lenalidomide (Revlimid®, also known as CC-5013) and pomalidomide (CC-4047) are IMiDs and chemical derivatives of thalidomide. Lenalidomide was introduced in 2004 and is currently approved for treatment of multiple myeloma and 5q-myelodysplastic syndromes (MDS). In addition, IMiDs are currently tested in a wide variety of haematological as well as solid tumours. IMiDs have three main anti-tumour properties, i.e. a direct anti-tumour effect, an inhibitory/modulatory effect on the tumour stroma/microenvironment supporting growth and survival of tumour cells including anti-angiogenic properties as well as a very potent immunomodulatory effect. The latter includes activation of T, NK and NKT cells as well as modulation of the function of mononuclear cells (DC and monocytes). However, the exact anti-cancer mechanisms of IMiDs in vivo remain elusive so far. This brief review will focus on the current concepts explaining the anti-cancer effects of IMiDs.