@article{VictoriaDonhauserVelosodeOliveiraSchicketal.2023, author = {Victoria Donhauser, Lara and Veloso de Oliveira, Julia and Schick, Cordula and Manlik, Wenzel and Styblova, Sabrina and Lutzenberger, Sarah and Aigner, Michael and Philipp, Patrick and Robert, Sebastian and Gandorfer, Beate and Hempel, Dirk and Hempel, Louisa and Zehn, Dietmar}, title = {Responses of patients with cancer to mRNA vaccines depend on the time interval between vaccination and last treatment}, series = {Journal for ImmunoTherapy of Cancer}, volume = {11}, journal = {Journal for ImmunoTherapy of Cancer}, number = {9}, doi = {10.1136/jitc-2023-007387}, year = {2023}, abstract = {Background Personalized mRNA vaccines are promising new therapeutic options for patients with cancer. Because mRNA vaccines are not yet approved for first-line therapy, the vaccines are presently applied to individuals that received prior therapies that can have immunocompromising effects. There is a need to address how prior treatments impact mRNA vaccine outcomes. Method Therefore, we analyzed the response to BioNTech/Pfizer's anti-SARS-CoV-2 mRNA vaccine in 237 oncology outpatients, which cover a broad spectrum of hematologic malignancies and solid tumors and a variety of treatments. Patients were stratified by the time interval between the last treatment and first vaccination and by the presence or absence of florid tumors and IgG titers and T cell responses were analyzed 14 days after the second vaccination. Results Regardless of the last treatment time point, our data indicate that vaccination responses in patients with checkpoint inhibition were comparable to healthy controls. In contrast, patients after chemotherapy or cortisone therapy did not develop an immune response until 6 months after the last systemic therapy and patients after Cht-immune checkpoint inhibitor and tyrosine kinase inhibitor therapy only after 12 months. Conclusion Accordingly, our data support that timing of mRNA-based therapy is critical and we suggest that at least a 6-months or 12-months waiting interval should be observed before mRNA vaccination in systemically treated patients.}, language = {en} } @article{HempelPiehlerGandorferetal.2022, author = {Hempel, Louisa and Piehler, Armin and Gandorfer, Beate and De Oliveira, Julia Veloso and Philipp, Patrick and Robert, Sebastian and Axel, Kleespies and Schick, Cordula and Fleischmann, Bastian and Schweneker, Katrin and Milani, Valeria and Schenk, Kristina and Ebner, Florian and Donhauser, Lara and Zehn, Dietmar and Hempel, Dirk}, title = {Clinical impact of SARS-CoV-2 delta variant infection in tumor patients and the impact of vaccination on different cancer treatment regimens.}, series = {Journal of Clinical Oncology}, volume = {40}, journal = {Journal of Clinical Oncology}, number = {16_suppl}, doi = {10.1200/JCO.2022.40.16_suppl.e18750}, pages = {E18750 -- E18750}, year = {2022}, abstract = {Background: Data on SARS-CoV-2 infections in oncological patients in the outpatient settings are scarce. Methods: During the spread of the delta variant between April 2021 and September 2021, a total of 10.677 patients were tested for SARS-CoV-2 infection by RT-qPCR in seven outpatient clinics in Bavaria, Germany. Results: Within the tested patient cohort, 4.960 patients (46.5\%) suffered from a malignant disease (74\% solid tumors and 26\% malignant hematological diseases). This group was compared with 5.717 patients (53.5\%) without a malignant disease (33.1\% with other hematological diseases and 66.9\% patients without a hematological or oncological disease). During the observation period, 119 (2.4\%) patients with malignancies were tested positive (88 patients with solid tumors; 31 patients with malignant hematological diseases) compared to 115 positive patients (2.0\%) in the control group. 32 of 119 positively tested patients (26.9\%) suffering from malignant disease required hospitalization and 9/32 patients (28.1\%) died during the clinical course. Conclusions: These observations are in clear contrast to data from patients we evaluated during the pre-delta variants period between 15 and 26 April 2020 in the same seven outpatient clinics. In this period, a total of 1.227 patients were tested for SARS-CoV-2 by RT-qPCR. 78/1227 patients (6.3\%) were tested positive in RT-qPCR and most showed mild symptoms of infection. None of the SARS-CoV-2 infected patients died. These data were analyzed when no vaccination was available. These data were evaluated during a period where no vaccine was available. Vaccination of patients with malignancies with BiontechPfizer's mRNA vaccines was started in April 2021. The response to the vaccine was tested by an antibody assay (Elecsys Anti-SARS-CoV-2 S-immunoassay, Roche) at the earliest four weeks after the second vaccination. To assess the response, we compared five patient cohorts: Patients who received (i) B cell depleting antibodies, (ii) checkpoint inhibitors (ICI), (iii) chemotherapy, or (iv) tyrosin kinase inhibitors (TKIs), and (v) healthy controls. The patients treated with ICI or TKI showed a comparable vaccination response to the healthy patients, while patients receiving Rituximab/Obinutuzumab showed no significant humoral vaccination response at all. The more severe disease course of patients infected by the SARS-CoV-2 delta variant compared to the initial waves of infections strongly underline the importance of vaccination in cancer patients.}, language = {en} } @article{HempelMolnarGaumannetal.2021, author = {Hempel, Louisa and Molnar, Jakob and Gaumann, Andreas and Robert, Sebastian and Scheiber, Josef and Kleespies, Axel and Riedmann, Kristina and Schreiber, Susanne and Gandorfer, Beate and Piehler, Armin and Hempel, Dirk}, title = {Detection of acquired resistance mutation ALK G1202R after treatment with alectinib and response of lorlatinib}, series = {memo - Magazine of European Medical Oncology}, journal = {memo - Magazine of European Medical Oncology}, year = {2021}, abstract = {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.}, language = {en} } @article{HempelPiehlerPfaffletal.2020, author = {Hempel, Louisa and Piehler, Armin and Pfaffl, Michael W. and Molnar, Jakob and Kirchner, Benedikt and Robert, Sebastian and Veloso, Julia and Gandorfer, Beate and Trepotec, Zeljka and Mederle, Stefanie and Keim, Sabine and Milani, Valeria and Ebner, Florian and Schweneker, Katrin and Fleischmann, Bastian and Kleespies, Axel and Scheiber, Josef and Hempel, Dirk and Zehn, Dietmar}, title = {SARS-CoV-2 infections in cancer outpatients—Most infected patients are asymptomatic carriers without impact on chemotherapy}, series = {Cancer Medicine}, volume = {9}, journal = {Cancer Medicine}, number = {21}, pages = {8020 -- 8028}, year = {2020}, abstract = {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.}, language = {en} } @article{HempelMolnarRobertetal.2021, author = {Hempel, Louisa and Molnar, Jakob and Robert, Sebastian and Veloso, Julia and Trepotec, Zeljka and Englisch, Sofie and Weinzierl, Philip and Schick, Cordula and Milani, Valeria and Schweneker, Katrin and Fleischmann, Bastian and Scheiber, Josef and Gandorfer, Beate and Kleespies, Axel and Hempel, Dirk and Riedmann, Kristina and Piehler, Armin}, title = {Rare SARS-CoV-2 antibody development in cancer patients}, series = {Seminars in Oncology}, volume = {48}, journal = {Seminars in Oncology}, number = {2}, pages = {160 -- 165}, year = {2021}, abstract = {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.}, language = {en} } @article{HempelVelosodeOliveiraGaumannetal.2021, author = {Hempel, Louisa and Veloso de Oliveira, Julia and Gaumann, Andreas and Milani, Valeria and Schweneker, Katrin and Schenck, Kristina and Fleischmann, Bastian and Philipp, Patrick and Mederle, Stefanie and Garg, Arun and Piehler, Armin and Gandorfer, Beate and Schick, Cordula and Kleespies, Axel and Sellmann, Ludger and Bartels, Marius and Goetze, Thorsten O. and Stein, Alexander and Goekkurt, Eray and Pfitzner, Lucia and Robert, Sebastian and Hempel, Dirk}, title = {Landscape of Biomarkers and Actionable Gene Alterations in Adenocarcinoma of GEJ and Stomach - A Real World Data Analysis}, series = {Cancers}, volume = {13}, journal = {Cancers}, number = {17}, pages = {4453}, year = {2021}, abstract = {After several years of negative phase III trials in gastric and esophageal cancer, a significant breakthrough in the treatment of metastatic adenocarcinomas of the gastroesophageal junction (GEJ) and stomach (GC) is now becoming evident with the emerging of precision oncology and implementation of molecular targets in tumor treatment. In addition, new generation studies such as umbrella and basket trials are focused on these molecular targets, which makes an early molecular diagnosis based on IHC/ISH and NGS necessary. The required companion diagnostics of Her2neu overamplification or PD-L1 expression is based on immunohistochemistry (IHC) or additionally in situ hybridization (ISH) in case of an IHC Her2neu score of 2+. However, there are investigator-dependent differences in the assessment of Her2neu amplification and different PD-L1 scoring systems obtained by IHC/ISH. The use of high-throughput technologies such as next-generation sequencing (NGS) holds the potential to standardize the analysis and thus make them more comparable. In the presented study, real-world multigene sequencing data of 72 Caucasian patients diagnosed with metastatic adenocarcinomas of GEJ and stomach were analyzed. In the clinical companion diagnostics, we found ESCAT level I molecular targets in one-third of our patients, which directly determined the therapy. In addition, we found potential targets in 14/72 patients (19.4\%) who potentially qualify for precision therapies in corresponding molecular studies. The study highlights the importance of comprehensive molecular profiling for precision treatment of GEJ/GC and indicates that a biomarker evaluation should be performed for all patients with metastatic adenocarcinomas before the initiation of first-line treatment and during second-line or subsequent treatment.}, language = {en} }