Article
Oncology
Lina Degenfeld-Schonburg, Susanne Gamperl, Gabriele Stefanzl, Anna-Katharina Schruef, Irina Sadovnik, Karin Bauer, Dubravka Smiljkovic, Gregor Eisenwort, Barbara Peter, Georg Greiner, Emir Hadzijusufovic, Juliana Schwaab, Wolfgang R. Sperr, Gregor Hoermann, Sonja Kopanja, Zsolt Szepfalusi, Konrad Hoetzenecker, Peter Jaksch, Andreas Reiter, Michel Arock, Peter Valent
Summary: Systemic mastocytosis (SM) is a complex hematopoietic neoplasm with clinical symptoms caused by organ infiltration by mast cells (MC) and the release of pro-inflammatory mediators. The growth and survival of MC in SM are triggered by various oncogenic mutant forms of the tyrosine kinase KIT, including the prevalent variant D816V. Two novel drugs, avapritinib and nintedanib, were found to effectively inhibit the growth and survival of neoplastic MC expressing different KIT mutant forms, including D816V, V560G, and K509I, making them potential candidates for the treatment of advanced SM.
AMERICAN JOURNAL OF CANCER RESEARCH
(2023)
Article
Biochemistry & Molecular Biology
Daniel J. DeAngelo, Deepti H. Radia, Tracy George, William A. Robinson, Albert T. Quiery, Mark W. Drummond, Prithviraj Bose, Elizabeth O. Hexner, Elliott F. Winton, Hans-Peter Horny, Meera Tugnait, Oleg Schmidt-Kittler, Erica K. Evans, Hui-Min Lin, Brenton G. Mar, Srdan Verstovsek, Michael W. Deininger, Jason Gotlib
Summary: The study evaluated the efficacy and safety of avapritinib in patients with AdvSM. Results showed that avapritinib induced deep and durable responses in patients at the recommended dose, demonstrating good tolerability.
Article
Hematology
Marcelo A. S. Toledo, Malrun Gatz, Stephanie Sontag, Karoline Gleixner, Gregor Eisenwort, Kristina Feldberg, Ahmed E. Hamouda, Frederick Kluge, Riccardo Guareschi, Giulia Rossetti, Antonio S. Sechi, Olli M. J. Dufva, Satu M. Mustjoki, Angela Maurer, Herdit M. Schueler, Roman Goetzke, Till Braunschweig, Anne Kaiser, Jens Panse, Mohamad Jawhar, Andreas Reiter, Frank Hilberg, Peter Ettmayer, Wolfgang Wagner, Steffen Koschmieder, Tim H. Bruemmendorf, Peter Valent, Nicolas Chatain, Martin Zenke
Summary: The KIT D816V mutation is a key therapeutic target for systemic mastocytosis, and nintedanib has been identified as a potential inhibitor for KIT D816V in patient-specific pluripotent stem cells.
Editorial Material
Hematology
Jason Gotlib, Andreas Reiter, Daniel J. DeAngelo
Summary: Avapritinib, a highly selective inhibitor of KIT D816V, has been approved for the treatment of advanced systemic mastocytosis (AdvSM). Clinical trials have shown that avapritinib can induce complete and durable responses in patients with AdvSM, including molecular remission of KIT D816V. However, managing the complex mutational landscape of AdvSM, often accompanied by hematologic neoplasms, poses challenges.
Article
Oncology
Mathias Schneeweiss-Gleixner, Yuksel Filik, Gabriele Stefanzl, Daniela Berger, Irina Sadovnik, Karin Bauer, Dubravka Smiljkovic, Gregor Eisenwort, Nadine Witzeneder, Georg Greiner, Gregor Hoermann, Ana-Iris Schiefer, Juliana Schwaab, Mohamad Jawhar, Andreas Reiter, Wolfgang R. Sperr, Michel Arock, Peter Valent, Karoline V. Gleixner
Summary: CDK4/CDK6 inhibitors show promising potential in suppressing the growth and survival of neoplastic mast cells and overcoming drug resistance. Additionally, they induce apoptosis in stem cells in AdvSM.
Article
Oncology
F. Janku, S. Bauer, K. Shoumariyeh, R. L. Jones, A. Spreafico, J. Jennings, C. Psoinos, J. Meade, R. Ruiz-Soto, P. Chi
Summary: This study demonstrates the efficacy and safety of Ripretinib in patients with KIT-altered metastatic melanoma. The drug shows promising results and may play a meaningful role in treating these patients.
Article
Biochemistry & Molecular Biology
Jose A. Lopez-Mejia, Luis F. Tallabs-Utrilla, Pablo Salazar-Sojo, Jessica C. Mantilla-Ollarves, Manuel A. Sanchez-Carballido, Leticia Rocha-Zavaleta
Summary: This study investigates the expression and effects of c-Kit in triple-negative breast cancer (TNBC) and finds that TNBC cells express functional c-Kit, which shows a strong response to Nilotinib and may be considered as a candidate drug for TNBC treatment.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Oncology
Hollie Pilkington, Sarah Smith, Neil Roskell, Sergio Iannazzo
Summary: This study compares the efficacy of avapritinib and midostaurin for patients with advanced systemic mastocytosis. The results suggest that avapritinib improves survival and treatment response compared to midostaurin.
Article
Hematology
Andreas Reiter, Juliana Schwaab, Daniel J. DeAngelo, Jason Gotlib, Michael W. Deininger, Kristen M. Pettit, Ivan Alvarez-Twose, Alessandro M. Vannucchi, Jens Panse, Uwe Platzbecker, Olivier Hermine, Ingunn Dybedal, Hui-Min Lin, Svetlana N. Rylova, Katrin Ehlert, Sasa Dimitrijevic, Deepti H. Radia
Summary: Avapritinib has shown high efficacy and safety in patients with AdvSM who had received prior systemic therapy, leading to significant clinical responses in the majority of patients with improvements in various growth indicators.
Article
Medicine, General & Internal
Aneta Szudy-Szczyrek, Oliwia Bachanek-Mitura, Tomasz Gromek, Karolina Chromik, Andrzej Mital, Michal Szczyrek, Witold Krupski, Justyna Szumilo, Zuzanna Kandula, Grzegorz Helbig, Marek Hus
Summary: Midostaurin has shown to be beneficial for patients with aggressive systemic mastocytosis (ASM), with most patients experiencing clinical improvement and objective response during the treatment course. Some patients also demonstrated a decrease in serum tryptase level and bone marrow infiltration cells during the treatment process.
JOURNAL OF CLINICAL MEDICINE
(2021)
Article
Oncology
Luna De Sutter, Agnieszka Wozniak, Jasper Verreet, Ulla Vanleeuw, Lore De Cock, Nina Linde, Christine Drechsler, Christina Esdar, Raf Sciot, Patrick Schoffski
Summary: In this study, the efficacy of a novel selective KIT inhibitor, IDRX-42, was tested in 4 GIST xenograft models. The results showed that IDRX-42 could cause tumor volume reduction, decrease mitotic activity, and induce myxoid degeneration in models with KIT exon 13 mutation. These findings indicate that IDRX-42 has significant antitumor activity in GIST.
CLINICAL CANCER RESEARCH
(2023)
Article
Medicine, Research & Experimental
Shuai Ye, Dinara Sharipova, Marya Kozinova, Lilli Klug, Jimson D'Souza, Martin G. Belinsky, Katherine J. Johnson, Margret B. Einarson, Karthik Devarajan, Yan Zhou, Samuel Litwin, Michael C. Heinrich, Ronald DeMatteo, Margaret von Mehren, James S. Duncan, Lori Rink
Summary: The management of Gastrointestinal Stromal Tumors (GISTs) has been greatly influenced by the identification of activating mutations in KIT and PDGFRA and the clinical application of RTK inhibitors. Despite the effectiveness of these inhibitors in most cases, resistance remains a clinical challenge, necessitating the identification of novel targets for refractory GISTs. Global kinome profiling shows promise in uncovering critical signaling networks and essential protein kinases in GISTs.
Editorial Material
Medicine, General & Internal
Caroline Burgard, Florian Rosar, Fadi Khreish, Samer Ezziddin
Summary: We report a case of a 68-year-old patient with systemic mastocytosis who underwent F-18-Fluorodeoxyglucose ([F-18]FDG) positron-emission tomography/computed tomography (PET/CT) before and after 6 months of midostaurin therapy. The post-therapeutic [F-18]FDG PET/CT showed decreased tracer uptake in the known gastrointestinal lesions, consistent with symptom relief and decreased serum tryptase level. Thus, [F-18]FDG PET/CT may be a potential method for monitoring the outcome of midostaurin therapy in systemic mastocytosis.
Article
Clinical Neurology
Bruno Dubois, Jesus Lopez-Arrieta, Stanley Lipschitz, Doskas Triantafyllos, Luiza Spiru, Svitlana Moroz, Olena Venger, Patrick Vermersch, Alain Moussy, Colin D. D. Mansfield, Olivier Hermine, Magda Tsolaki
Summary: The study found that the tyrosine kinase inhibitor masitinib, when administered orally, can be beneficial as an adjunct treatment for mild-to-moderate Alzheimer's disease. It showed significant improvement in cognitive and functional abilities, with side effects consistent with known information. Further research is ongoing to validate these results.
ALZHEIMERS RESEARCH & THERAPY
(2023)
Article
Oncology
Jian Li, Xinhua Zhang, Yanhong Deng, Xin Wu, Zhichao Zheng, Yongjian Zhou, Shirong Cai, Yanqiao Zhang, Jun Zhang, Kaixiong Tao, Yuehong Cui, Hui Cao, Kuntang Shen, Jiren Yu, Ye Zhou, Wenxiao Ren, Chenglin Qu, Wanqi Zhao, Jin Hu, Wei Wang, Jason Yang, Lin Shen
Summary: This study evaluated the safety and antineoplastic activity of Avapritinib in Chinese patients with unresectable/metastatic gastrointestinal stromal tumors. The results showed that Avapritinib had remarkable efficacy in patients with PDGFRA D842V mutations and notable efficacy as fourth- or later-line monotherapy.
Article
Medical Laboratory Technology
Vincent H. J. van der Velden, Frank Preijers, Ulrika Johansson, Theresia M. Westers, Alan Dunlop, Anna Porwit, Marie C. Bene, Peter Valent, Jeroen te Marvelde, Orianne Wagner-Ballon, Uta Oelschlaegel, Leonie Saft, Sharham Kordasti, Robin Ireland, Eline Cremers, Canan Alhan, Carolien Duetz, Willemijn Hobo, Nicolas Chapuis, Michaela Fontenay, Peter Bettelheim, Lisa Eidenshink-Brodersen, Patricia Font, Michael R. Loken, Sergio Matarraz, Kiyoyuki Ogata, Alberto Orfao, Katherina Psarra, Dolores Subira, Denise A. Wells, Matteo G. Della Porta, Kate Burbury, Frauke Bellos, Elisabeth Weiss, Wolfgang Kern, Arjan van de Loosdrecht
Summary: This article reviews the progress of flow cytometry (FCM) in the diagnosis of myelodysplastic syndrome (MDS) in recent years, and provides optimal methods and recommendations for sample processing, antibody panels and fluorochromes, and current hardware technologies. These recommendations will facilitate the appropriate application of FCM assays in the diagnostic workup of MDS patients, but further standardization and harmonization are needed.
CYTOMETRY PART B-CLINICAL CYTOMETRY
(2023)
Article
Medical Laboratory Technology
Theresia M. Westers, Leonie Saft, Vincent H. J. van der Velden, Jeroen G. te Marvelde, Alan Dunlop, Robin Ireland, Peter Valent, Anna Porwit, Marie C. Bene, Arjan A. van de Loosdrecht
Summary: This study described the diagnostic workflow of six cases using multimodal integrated diagnostics and demonstrated the application and added value of flow cytometry in patients with myelodysplastic syndrome.
CYTOMETRY PART B-CLINICAL CYTOMETRY
(2023)
Letter
Allergy
Matthew P. Giannetti, Francesco Olivieri, Grace Godwin, Emma Weller, Jennifer Nicoloro-SantaBarbara, Patrizia Bonadonna, Roberta Zanotti, Giovanna Zanoni, Karin Hartmann, Mariana Castells
Article
Allergy
Dubravka Smiljkovic, Harald Herrmann, Irina Sadovnik, Susanne Gamperl, Daniela Berger, Gabriele Stefanzl, Gregor Eisenwort, Gregor Hoermann, Sonja Kopanja, Yulia Dorofeeva, Margarete Focke-Tejkl, Peter Jaksch, Konrad Hoetzenecker, Zsolt Szepfalusi, Rudolf Valenta, Michel Arock, Peter Valent
Summary: Siglec-6 is identified as a surface antigen specifically expressed on human MC and basophils. Its expression is dynamically regulated and varies depending on cell types and activation factors. Understanding the expression changes of Siglec-6 provides insights into the function of MC and basophils in allergic reactions.
JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY
(2023)
Review
Allergy
Peter Valent, Amy D. Klion, Florence Roufosse, Dagmar Simon, Georgia Metzgeroth, Kristin M. Leiferman, Juliana Schwaab, Joseph H. Butterfield, Wolfgang R. Sperr, Karl Sotlar, Peter Vandenberghe, Gregor Hoermann, Torsten Haferlach, Richard Moriggl, Tracy George, Cem Akin, Bruce S. Bochner, Jason Gotlib, Andreas Reiter, Hans-Peter Horny, Michel Arock, Hans-Uwe Simon, Gerald J. Gleich
Summary: Eosinophilia and eosinophil activation are common in various diseases. They can lead to hypereosinophilia and hypereosinophilic syndrome, which can cause organ damage. The classification and criteria for these conditions have been widely accepted and regarded as standard since 2012. However, new developments in the field have created a need to update these criteria. A recent working conference on eosinophil disorders discussed new markers and concepts, aiming to improve the diagnosis and management of patients with hypereosinophilia and hypereosinophilic syndrome.
Review
Pathology
Peter Valent, Cem Akin, Wolfgang R. Sperr, Hans-Peter Horny, Michel Arock, Dean D. Metcalfe, Stephen J. Galli
Summary: Mastocytosis is a group of heterogeneous neoplasms characterized by an increase and accumulation of clonal mast cells in various organ systems. It can present as cutaneous mastocytosis or systemic mastocytosis, and the latter is further divided into different variants based on histopathological and molecular features, clinical variables, and organ involvement. The oncogenic machinery triggered by mutant forms of KIT plays a key role in MC expansion and disease progression, and genetic background, somatic mutations, and comorbidities also contribute to the course and prognosis. This article provides an update on the genetics, etiology, and pathology of mastocytosis, focusing on diagnostic criteria and new treatment concepts.
ANNUAL REVIEW OF PATHOLOGY-MECHANISMS OF DISEASE
(2023)
Article
Allergy
Johannes Luebke, Juliana Schwaab, Deborah Christen, Hanneke Oude Elberink, Bart Span, Marek Niedoszytko, Aleksandra Gorska, Magdalena Lange, Karoline V. Gleixner, Emir Hadzijusufovic, Oleksii Solomianyi, Irena Angelova-Fischer, Roberta Zanotti, Massimiliano Bonifacio, Patrizia Bonadonna, Khalid Shoumariyeh, Nikolas von Bubnoff, Sabine Mueller, Cecelia Perkins, Chiara Elena, Luca Malcovati, Hans Hagglund, Mattias Mattsson, Roberta Parente, Judit Varkonyi, Anna Belloni Fortina, Francesca Caroppo, Alexander Zink, Knut Brockow, Christine Breynaert, Dominique Bullens, Akif Selim Yavuz, Michael Doubek, Vito Sabato, Tanja Schug, Dietger Niederwieser, Karin Hartmann, Massimo Triggiani, Jason Gotlib, Olivier Hermine, Michel Arock, Hanneke C. Kluin-Nelemans, Jens Panse, Wolfgang R. Sperr, Peter Valent, Andreas Reiter, Mohamad Jawhar
Summary: Organomegaly, including splenomegaly, hepatomegaly, and/or lymphadenopathy, is an important diagnostic and prognostic feature in patients with cutaneous mastocytosis (CM) or systemic mastocytosis (SM). The number of organomegalies is adversely associated with overall survival (OS), and lymphadenopathy is frequently detected in patients with SM, particularly in advanced SM (AdvSM). The presence of lymphadenopathy in AdvSM is associated with inferior outcomes compared to AdvSM patients without lymphadenopathy.
JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY-IN PRACTICE
(2023)
Article
Biochemistry & Molecular Biology
Sai Nivedita Krishnan, Thatchawan Thanasupawat, Leanne Arreza, G. William Wong, Karen Sfanos, Bruce Trock, Michel Arock, Girish Shah, Aleksandra Glogowska, Saeid Ghavami, Sabine Hombach-Klonisch, Thomas Klonisch
Summary: CTRP8 is a novel marker of tryptase+ mast cells in normal human tissues and in the prostate cancer microenvironment. CTRP8 promotes cell motility, matrix invasion, and drug resistance through the interaction with the relaxin receptor RXFP1. Higher numbers of CTRP8+ mast cells are associated with biochemical recurrence in prostate cancer.
BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR BASIS OF DISEASE
(2023)
Article
Dermatology
Hanna Wassmer, Karin Hartmann
Summary: Mastocytosis in children is a rare disease characterized by an abnormal accumulation of tissue mast cells. It mainly presents with typical skin alterations and mast cell mediator symptoms, such as pruritus, flush, and anaphylaxis. Most cases have a benign and self-limiting course, while systemic mastocytosis with extracutaneous involvement is rare. Treatment includes H1 antihistamines and educating children, parents, and caregivers about the disease.
Meeting Abstract
Allergy
Cem Akin, Frank Siebenhaar, Jason Gotlib, Mariana Castells, Stephane Barete, Ivan Alvarez-Twose, Cristina Bulai Livideanu, Vito Sabato, Paul Van Daele, Thanai Pongdee, Brant Ward, Peter Vadas, Prithviraj Bose, Pankit Vachhani, Massimo Triggiani, Patrizia Bonadonna, Karin Hartmann, Stephen Oh, Mar Guilarte, Andrew Kuykendall, Cecilia Arana Yi, Princess Ogbogu, Sigurd Broesby-Olsen, Caroline Gaudy, Matthew Giannetti, Hui-Min Lin, Robyn Scherber, Maria Roche, Marcus Maurer, Hanneke Elberink
JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY
(2023)
Meeting Abstract
Allergy
Mariana Castells, Jason Gotlib, Hanneke Oude Elberink, Frank Siebenhaar, Karin Hartmann, Sigurd Broesby-Olsen, Tracy George, Jens Panse, Ivan Alvarez-Twose, Deepti Radia, Tsewang Tashi, Cristina Bulai Livideanu, Vito Sabato, Paul Van Daele, Sonia Cerquozzi, Ingunn Dybedal, Andreas Reiter, Thanai Pongdee, Stephane Barete, Lawrence Schwartz, Prithviraj Bose, Massimo Triggiani, William Shomali, Matthew Giannetti, Ilda Bidollari, Hui-Min Lin, Robyn Scherber, Maria Roche, Cem Akin, Marcus Maurer
JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY
(2023)
Meeting Abstract
Allergy
Karin Hartmann, Vito Sabato, Jonathan Bernstein, Cristina Bulai Livideanu, Patricia Lugar, Albert Hirdt, Ivan Alvarez-Twose, Aaron Zakharyan, Tiffany Ashton, Gerard Hoehn, Cem Akin
JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY
(2023)
Article
Oncology
Lina Degenfeld-Schonburg, Susanne Gamperl, Gabriele Stefanzl, Anna-Katharina Schruef, Irina Sadovnik, Karin Bauer, Dubravka Smiljkovic, Gregor Eisenwort, Barbara Peter, Georg Greiner, Emir Hadzijusufovic, Juliana Schwaab, Wolfgang R. Sperr, Gregor Hoermann, Sonja Kopanja, Zsolt Szepfalusi, Konrad Hoetzenecker, Peter Jaksch, Andreas Reiter, Michel Arock, Peter Valent
Summary: Systemic mastocytosis (SM) is a complex hematopoietic neoplasm with clinical symptoms caused by organ infiltration by mast cells (MC) and the release of pro-inflammatory mediators. The growth and survival of MC in SM are triggered by various oncogenic mutant forms of the tyrosine kinase KIT, including the prevalent variant D816V. Two novel drugs, avapritinib and nintedanib, were found to effectively inhibit the growth and survival of neoplastic MC expressing different KIT mutant forms, including D816V, V560G, and K509I, making them potential candidates for the treatment of advanced SM.
AMERICAN JOURNAL OF CANCER RESEARCH
(2023)
Article
Oncology
Juliana Schwaab, Hans-Peter Horny, Karin Hartmann
Summary: Systemic mastocytosis (SM) is a clonal stem cell disorder with a wide range of clinical manifestations and a heterogeneous prognosis. This review explores the challenges in diagnosis, prognostic models, and therapeutic options for this rare disease. The elevated serum tryptase levels are a diagnostic criterion of SM and symptomatic therapy may be applied in all patients. Novel KIT inhibitors have significantly improved overall survival and symptoms in advanced phase disease (AdvSM) patients, and allogeneic stem cell transplantation remains the only curative option.
Article
Allergy
Peter Schmid-Grendelmeier, Melinda J. Gooderham, Karin Hartmann, George N. Konstantinou, Marc Fellmann, Christopher Koulias, Claire Clibborn, Pinaki Biswas, Patrick M. Brunner
Summary: This article evaluated the efficacy and safety of abrocitinib in patients with moderate-to-severe atopic dermatitis and allergic comorbidities. The results showed that abrocitinib was effective and safe in managing atopic dermatitis in patients with or without allergic comorbidities.