Secondary resistance to idelalisib is characterized by upregulation of IGF1R rather than by MAPK/ERK pathway mutations
Eugen Tausch, Viktor Ljungström, Andreas Agathangelidis, Marc Zapatka, Lydia Scarfò, Billy Michael Chelliah Jebaraj, Deyan Y. Yosifov, Annika Müller, Veerendra Munugalavadla, Jeremiah D. Degenhardt, Paolo Ghia, Richard Rosenquist, Stephan Stilgenbauer
Abstract
Letter to Blood| June 2, 2022 Secondary resistance to idelalisib is characterized by upregulation of IGF1R rather than by MAPK/ERK pathway mutations Eugen Tausch, Eugen Tausch Division of Chronic Lymphocytic Leukemia, Department of Internal Medicine III, Ulm University, Ulm, Germany; Search for other works by this author on: This Site PubMed Google Scholar Viktor Ljungström, Viktor Ljungström Department of Immunology, Genetics and Pathology, Science for Life Laboratory, Uppsala University, Uppsala, Sweden; Search for other works by this author on: This Site PubMed Google Scholar Andreas Agathangelidis, Andreas Agathangelidis Università Vita-Salute San Raffaele and Ospedale San Raffaele, Milan, Italy;Department of Biology, School of Science, National and Kapodistrian University of Athens, Athens, Greece; Search for other works by this author on: This Site PubMed Google Scholar Marc Zapatka, Marc Zapatka German Cancer Research Center, Heidelberg, Germany; https://orcid.org/0000-0001-8287-5967 Search for other works by this author on: This Site PubMed Google Scholar Lydia Scarfò, Lydia Scarfò Università Vita-Salute San Raffaele and Ospedale San Raffaele, Milan, Italy; Search for other works by this author on: This Site PubMed Google Scholar Billy Michael Chelliah Jebaraj, Billy Michael Chelliah Jebaraj Division of Chronic Lymphocytic Leukemia, Department of Internal Medicine III, Ulm University, Ulm, Germany; Search for other works by this author on: This Site PubMed Google Scholar Deyan Y. Yosifov, Deyan Y. Yosifov Division of Chronic Lymphocytic Leukemia, Department of Internal Medicine III, Ulm University, Ulm, Germany;German Cancer Research Center, Heidelberg, Germany; https://orcid.org/0000-0002-5473-4398 Search for other works by this author on: This Site PubMed Google Scholar Annika Müller, Annika Müller Division of Chronic Lymphocytic Leukemia, Department of Internal Medicine III, Ulm University, Ulm, Germany; Search for other works by this author on: This Site PubMed Google Scholar Veerendra Munugalavadla, Veerendra Munugalavadla Translational Medicine, Hematology Research and Development, AstraZeneca, South San Francisco, CA; Search for other works by this author on: This Site PubMed Google Scholar Jeremiah D. Degenhardt, Jeremiah D. Degenhardt Research and Development, Maverick Therapeutics, Brisbane, CA; Search for other works by this author on: This Site PubMed Google Scholar Paolo Ghia, Paolo Ghia Università Vita-Salute San Raffaele and Ospedale San Raffaele, Milan, Italy; https://orcid.org/0000-0003-3750-7342 Search for other works by this author on: This Site PubMed Google Scholar Richard Rosenquist, Richard Rosenquist Department of Molecular Medicine and Surgery, Karolinska Institutet, Stockholm, Sweden; andClinical Genetics, Karolinska University Laboratory, Karolinska University Hospital, Stockholm, Sweden Search for other works by this author on: This Site PubMed Google Scholar Stephan Stilgenbauer Stephan Stilgenbauer Division of Chronic Lymphocytic Leukemia, Department of Internal Medicine III, Ulm University, Ulm, Germany; Search for other works by this author on: This Site PubMed Google Scholar Blood (2022) 139 (22): 3340–3344. https://doi.org/10.1182/blood.2021014550 Article history Submitted: October 26, 2021 Accepted: March 11, 2022 First Edition: April 4, 2022 Share Icon Share Facebook Twitter LinkedIn MailTo Tools Icon Tools Request Permissions Cite Icon Cite Search Site Citation Eugen Tausch, Viktor Ljungström, Andreas Agathangelidis, Marc Zapatka, Lydia Scarfò, Billy Michael Chelliah Jebaraj, Deyan Y. Yosifov, Annika Müller, Veerendra Munugalavadla, Jeremiah D. Degenhardt, Paolo Ghia, Richard Rosenquist, Stephan Stilgenbauer; Secondary resistance to idelalisib is characterized by upregulation of IGF1R rather than by MAPK/ERK pathway mutations. Blood 2022; 139 (22): 3340–3344. doi: https://doi.org/10.1182/blood.2021014550 Download citation file: Ris (Zotero) Reference Manager EasyBib Bookends Mendeley Papers EndNote RefWorks BibTex toolbar search Search Dropdown Menu toolbar search search input Search input auto suggest filter your search All ContentAll JournalsBlood Search Subjects: Lymphoid Neoplasia TO THE EDITOR: With great interest we read a recent publication in Blood by Murali et al demonstrating somatic mutations in the MAPK/extracellular signal-regulated kinase (ERK) pathway in 60% of patients with chronic lymphocytic leukemia (CLL) with primary resistance to PI3K inhibitors.1 Different trials have underlined the efficacy of the PI3Kδ inhibitor idelalisib in combination with CD20 antibodies, such as rituximab, and charted a safety profile superior to therapies containing conventional chemotherapeutic drugs.2-4 Furthermore, next-generation PI3K inhibitors, such as copanlisib or umbralisib, promise high efficacy in lymphoid malignancies.5,6 Therefore, the understanding of resistance to PI3K inhibitors remains an important task to investigate. Furthermore, there may be differences between primary resistance with refractoriness at treatment initiation and secondary resistance, which is acquired during several months of treatment after initial response to therapy. To this purpose, we selected patients... REFERENCES 1.Murali I, Kasar S, Naeem A, et al. Activation of the MAPK pathway mediates resistance to PI3K inhibitors in chronic lymphocytic leukemia. Blood. 2021;138(1):44-56.Google ScholarCrossrefSearch ADS PubMed 2.Furman RR, Sharman JP, Coutre SE, et al. Idelalisib and rituximab in relapsed chronic lymphocytic leukemia. N Engl J Med. 2014;370(11):997-1007.Google ScholarCrossrefSearch ADS PubMed 3.Jones JA, Robak T, Brown JR, et al. Efficacy and safety of idelalisib in combination with ofatumumab for previously treated chronic lymphocytic leukaemia: an open-label, randomised phase 3 trial. Lancet Haematol. 2017;4(3):e114-e126.Google ScholarCrossrefSearch ADS PubMed 4.Sharman JP, Coutre SE, Furman RR, et al. 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Haematologica. 2019;104(9):e434-e437.Google ScholarCrossrefSearch ADS PubMed © 2022 by The American Society of Hematology2022 You do not currently have access to this content. Sign in via your Institution