TY - JOUR A1 - Hempel, Louisa A1 - Molnar, Jakob A1 - Gaumann, Andreas A1 - Robert, Sebastian A1 - Scheiber, Josef A1 - Kleespies, Axel A1 - Riedmann, Kristina A1 - Schreiber, Susanne A1 - Gandorfer, Beate A1 - Piehler, Armin A1 - Hempel, Dirk T1 - Detection of acquired resistance mutation ALK G1202R after treatment with alectinib and response of lorlatinib BT - A case report JF - memo - Magazine of European Medical Oncology N2 - In the era of personalized medicine, the identification of driver mutations has paved the way towards targeted therapy. With the identification of anaplastic lymphoma kinase (ALK) as an oncogenic driver mutation, ALK rearrangements became druggable by tyrosine kinase inhibitors and, thus, have improved the prognosis for patients. Nevertheless, these approaches are limited by resistances occurring within the first or second year of administering ALK inhibitors. Among the different ALK resistant mutations, G1202R is the most common mutation, located in the kinase domain of the ALK protein resulting in resistance to treatment with the first- and second-generation kinase inhibitors (e.g., crizotinib, ceritinib, brigatenib and alectinib). Conflicting reports exist regarding the efficacy of lorlatinib, a next generation ALK inhibitor. The aim of this study is to access the potential impact of lorlatinib as a second-line treatment for a metastatic progressive NSCLC disease harboring genomic alteration of ALK G1202R, an AKLi-resistant mutation. The case of a patient with advanced lung cancer and the mentioned mutation is described. KW - NSCLC KW - Next-generation ALK inhibitor KW - Resistance mechanisms KW - Next-generation sequencing KW - Molecular diagnostics Y1 - 2021 UR - https://doi.org/10.1007/s12254-021-00724-2 ER - TY - JOUR A1 - Hempel, Louisa A1 - Molnar, Jakob A1 - Robert, Sebastian A1 - Veloso, Julia A1 - Trepotec, Zeljka A1 - Englisch, Sofie A1 - Weinzierl, Philip A1 - Schick, Cordula A1 - Milani, Valeria A1 - Schweneker, Katrin A1 - Fleischmann, Bastian A1 - Scheiber, Josef A1 - Gandorfer, Beate A1 - Kleespies, Axel A1 - Hempel, Dirk A1 - Riedmann, Kristina A1 - Piehler, Armin T1 - Rare SARS-CoV-2 antibody development in cancer patients JF - Seminars in Oncology N2 - SARS-CoV-2 antibody development and immunity will be crucial for the further course of the pandemic. Until now, it has been assumed that patients who are infected with SARS-CoV-2 will develop antibodies as has been the case with other coronaviruses, like MERS-CoV and SARS-CoV. In the present study, we analyzed the development of antibodies in 77 patients with an oncologic diagnosis 26 days after positive RT-qPCR testing for SARS-CoV2. RT-qPCR and anti-SARS-CoV2-antibody methods from BGI (MGIEasy Magnetic Beads Virus DNA/RNA Extraction Kit) and Roche (Elecsys Anti-SARS-CoV-2 immunoassay) were used, respectively, according to the manufacturers’ specifications. Surprisingly, antibody development was detected in only 6 of 77 individuals with a confirmed history of COVID-19. Despite multiple testing, the remaining patients did not show measurable antibody concentrations in subsequent tests. These results undermine the previous hypothesis that SARS-CoV2 infections are regularly associated with antibody development and cast doubt on the provided immunity to COVID-19. Understanding the adaptive and humoral response to SARS-CoV2 will play a key role in vaccine development and gaining further knowledge on the pathogenesis. KW - SARS-CoV2 antibody development KW - COVID-19 KW - Cancer KW - Immunity Y1 - 2021 UR - https://doi.org/10.1053/j.seminoncol.2020.12.003 VL - 48 IS - 2 SP - 160 EP - 165 ER - TY - JOUR A1 - Hempel, Louisa A1 - Piehler, Armin A1 - Pfaffl, Michael W. A1 - Molnar, Jakob A1 - Kirchner, Benedikt A1 - Robert, Sebastian A1 - Veloso, Julia A1 - Gandorfer, Beate A1 - Trepotec, Zeljka A1 - Mederle, Stefanie A1 - Keim, Sabine A1 - Milani, Valeria A1 - Ebner, Florian A1 - Schweneker, Katrin A1 - Fleischmann, Bastian A1 - Kleespies, Axel A1 - Scheiber, Josef A1 - Hempel, Dirk A1 - Zehn, Dietmar T1 - SARS-CoV-2 infections in cancer outpatients—Most infected patients are asymptomatic carriers without impact on chemotherapy JF - Cancer Medicine N2 - Oncologic patients are regarded as the population most at risk of developing a severe course of COVID-19 due to the fact that malignant diseases and chemotherapy often weaken the immune system. In the face of the ongoing SARS-CoV-2 pandemic, how particular patients deal with this infection remains an important question. In the period between the 15 and 26 April 2020, a total of 1227 patients were tested in one of seven oncologic outpatient clinics for SARS-CoV-2, regardless of symptoms, employing RT-qPCR. Of 1227 patients, 78 (6.4%) were tested positive of SARS-CoV-2. Only one of the patients who tested positive developed a severe form of COVID-19 with pneumonia (CURB-65 score of 2), and two patients showed mild symptoms. Fourteen of 75 asymptomatic but positively tested patients received chemotherapy or chemo-immunotherapy according to their regular therapy algorithm (±4 weeks of SARS-CoV-2 test), and 48 of 78 (61.5%) positive-tested patients received glucocorticoids as co-medication. None of the asymptomatic infected patients showed unexpected complications due to the SARS-CoV-2 infection during the cancer treatment. These data clearly contrast the view that patients with an oncologic disease are particularly vulnerable to SARS-CoV-2 and suggest that compromising therapies could be continued or started despite the ongoing pandemic. Moreover the relatively low appearance of symptoms due to COVID-19 among patients on chemotherapy and other immunosuppressive co-medication like glucocorticoids indicate that suppressing the response capacity of the immune system reduces disease severity. KW - COVID-19 Y1 - 2021 UR - https://doi.org/10.1002/cam4.3435 VL - 9 IS - 21 SP - 8020 EP - 8028 ER -