memo - Magazine of European Medical Oncology

2018 memo - Magazine of European Medical Oncology

doi: 10.1007/s12254-018-0425-x

Webersinke, Gerald

2018 memo - Magazine of European Medical Oncology

doi: 10.1007/s12254-018-0399-8

Fuereder, Thorsten

2018 memo - Magazine of European Medical Oncology

doi: 10.1007/s12254-018-0412-2

Heintel, Daniel

2018 memo - Magazine of European Medical Oncology

doi: 10.1007/s12254-018-0417-x

Vockenhuber, Michael; Wiesinger, Kurt; Gruber, Christine

2018 memo - Magazine of European Medical Oncology

doi: 10.1007/s12254-018-0400-6

Proliferation or reduction of one or more cell lines in the peripheral blood count, occurrence of cells not normally found in the peripheral blood (e.g., blast cells, red precursors), suspicious laboratory findings (e.g., paraproteins, free light chains), lymphadenopathy of unclear origin, or other clinical signs (e.g., fever, B‑symptoms, bone pain) are indicators of hematologic disease.

Burger, Sabine; Zojer, Niklas; Ludwig, Heinz

2018 memo - Magazine of European Medical Oncology

doi: 10.1007/s12254-018-0407-z

At the 2017 American Society of Hematology Meeting promising data were presented reflecting the impressing advances of clinical research in multiple myeloma. In fit patients eligible for autologous stem cell transplantation new induction regimens showed high response and minimal residual disease negativity rates. Again the important role of autologous stem cell transplantation was pointed out especially for patients with high risk cytogenetics. In the relapsed setting intensified combination therapies are related with improvement of PFS (progression free survival) and even OS (overall survival). Concerning maintenance therapy significant benefits in all standard, high and ultra-high risk groups of patients could be demonstrated. New developements like Selinexor, Filanesib and CAR (chimeric antigen receptor) T cells showed impressing results in a heavily pretreated population.

Geissler, Klaus

2018 memo - Magazine of European Medical Oncology

doi: 10.1007/s12254-018-0406-0

Despite remarkable achievements in the management of chronic myeloid leukemia (CML), there remain a number of challenges in the field. At the American Society of Hematology (ASH) Meeting 2017 several presentations addressed current problems around the topics CML stem cells, progression of CML into blast crisis (BC), and personalized treatment.

Pfeilstöcker, Michael

2018 memo - Magazine of European Medical Oncology

doi: 10.1007/s12254-018-0410-4

Nösslinger, Thomas

2018 memo - Magazine of European Medical Oncology

doi: 10.1007/s12254-018-0398-9

At the last ASH (American Society of Hematology) meeting a new prognostic tool for follicular lymphoma (FL), based on the patient cohort of the PRIMA trial (PRIMA-PI, Primary Rituximab and Maintenance-Prognostic Index), was presented. The 10-year update of the PRIMA trial confirms the continuous advantage in progression-free survival of rituximab maintenance after R‑CHOP induction without new safety signals. Similarly rituximab maintenance is beneficial in FL after first-line chemoimmunotherapy with rituximab–bendamustine. Currently checkpoint inhibitors are under investigation in different treatment lines of FL. The earlier ibrutinib is administered in relapsed mantle cell lymphoma, the more effective the long-term efficacy is. New, more selective inhibitors of the Bruton’s tyrosine kinase (BTK) may be an option for patients in whom ibrutinib may be contraindicated.

Wanner, David; Steurer, Michael

2018 memo - Magazine of European Medical Oncology

doi: 10.1007/s12254-018-0414-0pmid: 29983825

At ASH (American Society of Hematology) 2017 three out of a plethora of trials showed remarkable and promising results. The combinations of venetoclax with rituximab and ibrutinib with venetoclax convinced with striking efficacy together with a manageable safety profile in relapsed/refractory setting as well as in first line therapy of high-risk disease. These two combinations are potential new standard treatment options in chronic lymphocytic leukemia.

Fuchs, David; Fridrik, Michael

2018 memo - Magazine of European Medical Oncology

doi: 10.1007/s12254-018-0413-1

Combined-modality treatment with chemo-immunotherapy and radiotherapy produces excellent outcomes in early-stage, non-bulky diffuse large B‑cell lymphoma, and reducing toxicity of therapy is a major concern, especially in elderly patients. In a recent trial, elderly patients with non-bulky (<7.5 cm) in complete metabolic remission after four courses of therapy (rituximab, cyclophosphamide, doxorubicine, vincristine, prednisone [R‑CHOP-14] based) were spared additional chemotherapy and went on to receive four cycles of rituximab only, while all other patients continued on chemo-immunotherapy. The 2‑year overall survival was 98%, which matches historical controls. In another analysis from the same trial, elderly patients with bulky disease in positrone emission tomography (PET) based CR (complete remission) after six cycles of chemo-immunotherapy were spared radiotherapy, while PET-positive patients were irradiated. This approach resulted in a significant reduction (42%) of radiotherapy compared to historical controls without compromising efficacy. Radiotherapy could also be omitted in patients of any age with limited stage, non-bulky disease in another trial, with a 5-year event-free survival of 89% and an overall survival of 92%. Another burning issue is enhancing efficacy in relapsed and refractory diffuse large B‑cell lymphoma. Arguably the most exciting approach in this area is chimeric-antigen-receptor T‑cell therapy. Recent trials have shown nearly 10-fold increases in complete responses compared to historical controls, and most importantly, a high percentage (40%) of durable remissions after one year of follow-up. As in other advances in immunotherapy, toxicity is a major concern. Cytokine release syndrome occurs frequently (1–18% grade 3–4) and management is complex, sometimes requiring admission to intensive care and often including the interleukin-6 receptor antibody tocilizumab.

Tiefenbacher, Andreas; Pirker, Robert

2018 memo - Magazine of European Medical Oncology

doi: 10.1007/s12254-018-0408-ypmid: 29983826

Patients with advanced non-small cell lung cancer receive first-line therapy with chemotherapy, targeted therapies in case of tumors with driver mutations, and more recently also immune checkpoint inhibitors. Important controversies include the role of targeted therapies in combination with chemotherapy, optimal sequencing of treatments, treatment guidance by means of predictive biomarkers, and value-based judgements of treatments.

Wohlfarth, Philipp; Worel, Nina; Hopfinger, Georg

2018 memo - Magazine of European Medical Oncology

doi: 10.1007/s12254-018-0409-xpmid: 29983827

Chimeric antigen receptor (CAR) T cells are genetically engineered autologous cells that express an activating receptor targeted towards one or more tumoral antigens. After ex vivo production and re-infusion, they are able to proliferate in the host and to recognize and kill tumor cells. Together with checkpoint inhibition, this new therapy is already being celebrated as a major medical breakthrough in recent years, due to the substantial benefit observed in clinical trials with patients with chemotherapy-refractory B‑cell malignancies. These results have led to the recent approval of two CAR T‑cell products by the Food and Drug Administration (FDA) in the United States. The list of targetable antigens and possible indications is continuously being expanded, as are the modifications to the CAR structure and the final cell products currently under investigation. In some patients, CAR T‑cell therapy may lead to substantial toxicity including the cytokine release syndrome (CRS). In summary, CAR T‑cell therapy has already provided clinical benefit to patients with B‑cell malignancies unresponsive to conventional treatment. Yet, the therapy is still in an early stage of development, and the many opportunities for improvement in its various aspects as well as its future role in relation to conventional therapy will set the pace in the field of hematology for the next years or even decades.

Mauti, Laetitia; Finazzi, Tobias; Früh, Martin; Pless, Miklos; Zippelius, Alfred; Rothschild, Sacha

2018 memo - Magazine of European Medical Oncology

doi: 10.1007/s12254-018-0411-3

Lung cancer is the leading cause of cancer-associated death worldwide. Traditionally, lung cancer is classified into non-small cell lung cancer (NSCLC) and small cell lung cancer (SCLC). While the prognosis of metastatic SCLC has remained dismal, the outcome of advanced NSCLC has improved over the last decades mainly by the improved molecular characterization of the disease and the introduction of targeted therapies in well-defined subpopulations. However, even in localized or locally advanced lung cancer many patients eventually have a relapse and will die of their disease. Therefore, novel treatment approaches are urgently needed. Lung cancer is generally characterized by high frequencies of genetic and epigenetic alterations resulting in tumor-associated antigens which are potential targets of cytotoxic T cells. Immune checkpoint inhibitors (ICIs) have shown to re-activate and improve this specific T cell response. Several clinical trials have demonstrated meaningful response rates, sustained clinical benefit with encouraging survival rates and good tolerability in advanced NSCLC and have established ICIs as a new standard of care in different indications. This article summarizes the current evidence for ICIs in early and advanced NSCLC as well as in SCLC. Furthermore, current data and ongoing clinical trials on combination therapies are discussed as well as challenges of immunotherapy in lung cancer patients.

Rudzki, Jakob

2018 memo - Magazine of European Medical Oncology

doi: 10.1007/s12254-018-0416-ypmid: 29983828

IO treatments (immuno-oncology treatments) have become reality and are now daily practice or, in some cases, a daily challenge. New recommendations are being made with the prime purpose of increasing alertness and awareness as well as emphasizing standard operating strategies to deal with immune-related adverse events (ir-AEs) in patients treated with immune checkpoint inhibitors (ICI). This brief review refers to systemic reviews, guidelines and meta-analyses, randomized controlled trials and case series published from 2000 to the present. Existing recommendations for optimal management of toxicities vary according to organ systems affected and grading. Grade 1 toxicities (exception to the rule: neurologic, hematologic, cardiac manifestation) require close monitoring. Grade 2 toxicities prompt immediate treatment interruption combined with corticosteroid administration (prednisone or methylprednisolone 0.5–1 mg/kg/day) until the symptoms revert to grade 1 or less. ir-AEs up to grade 3 or 4 justify suspension of treatment together with increased dosage of prednisone or methylprednisolone (1–2 mg/kg/day) combined with close monitoring to continuously adapt the current immunosuppressive strategy. In some cases, a different additional immunosuppressive agent has to be evaluated. Only when all symptoms have disappeared and immunosuppressive treatment produces a response can all immunosuppressive agents be tapered. Endocrinopathies are the exception to the rule and are mostly controllable by hormone replacement, at least in low-grade manifestation. This short review focuses on the main aspects that help manage immune-related side-effects and elucidates all the additional aspects surrounding and contributing to successful treatment and management of cancer patients.

Beer, Lucian; Hochmair, Maximilian; Prosch, Helmut

2018 memo - Magazine of European Medical Oncology

doi: 10.1007/s12254-018-0389-xpmid: 29983829

Immunotherapies comprise of a class of cancer therapies that are increasingly used for treatment of several cancer entities. Active immunotherapies encompassing immune checkpoint inhibitors are the most widespread class of immunotherapies, with indications for melanoma, non-small lung cancer, renal cell carcinoma, urothelial carcinoma, head and neck squamous cell carcinoma, and Hodgkin’s lymphoma. Immune checkpoint inhibitors have demonstrated unique response patterns that are not adequately captured by traditional response criteria such das the Response Evaluation Criteria in Solid Tumors (RECIST) and World Health Organization criteria. Consequently, adaptions of these criteria have been released such as the immune-related RECIST and immune RECIST, which account for the specialities of immunotherapies. Immunotherapies can cause a distinct set of adverse events such as pneumonitis, colitis, and hypophysitis. In addition, atypical treatment response patterns termed pseudoprogression have been observed. Thereby, new or enlarging lesions appear after treatment start and mimic tumor progression, which is followed by an eventual decrease in total tumor burden. In this review article we will describe pitfalls in the radiological response assessment of immunotherapies, focusing on pseudoprogression and imaging appearances of common immune-related adverse events.

Berbec, Nicoleta; Stanculeanu, Dana; Badelita, Nicoleta; Vasilica, Mariana; Popovici, Dorel; Colita, Andrei; Neacsu, Cristina; Iordan, Alexandru

2018 memo - Magazine of European Medical Oncology

doi: 10.1007/s12254-018-0390-4pmid: 29983830

Bagheropur, Soheila; Ehsanpour, Ali; Birgani, Maryam; Saki, Najmaldin

2018 memo - Magazine of European Medical Oncology

doi: 10.1007/s12254-018-0397-x

Philadelphia chromosome-negative myeloproliferative neoplasms (MPNs), including polycythemia vera (PV), essential thrombocythemia (ET), and primary myelofibrosis (PMF), are characterized by mutations in genes, such as JAK2V617F, JAK2 exon12 gene and MPL. With respect to MPN-associated subclasses, each of these disorders has a different allele burden during disease treatment. Up to now, several studies have been conducted on the relationship between allele burden with specific MPN-associated phenotypic features, prognosis and disease progression. It seems that finding such a correlation would be a great contribution to faster diagnosis and effective treatment. The goal of this review is to investigate the relationship between JAK2V617 allele burden with different MPN subtypes and their different phenotypes. Allele burden is closely associated with MPN phenotype and can partially indicate the prognosis, progression and even the likelihood of disease transformation.

De haes, Inke; Valcke, Yvan; Deschepper, Koen; Beerens, Elisabeth; Goeminne, Pieter

2018 memo - Magazine of European Medical Oncology

doi: 10.1007/s12254-018-0404-2