Mivavotinib for Relapsed/Refractory B-cell Lymphoma (Updated)



February 1, 2023

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  • Oncotarget published this research paper in Volume 14, entitled, “Spleen tyrosine kinase/FMS-like tyrosine kinase-3 inhibition in relapsed/refractory B-cell lymphoma, including diffuse large B-cell lymphoma: updated data with mivavotinib (TAK-659/CB-659)" by the researchers from the Division of Hematology and Oncology, Northwestern University Feinberg School of Medicine and the Robert H. Lurie Comprehensive Cancer Center, Chicago, IL; Department of Haematology, NIHR/UCLH Clinical Research Facility, University College London Hospitals NHS Foundation Trust, London, UK; Drug Development, Sarah Cannon Research Institute/Tennessee Oncology, Nashville, TN; Dipartimento di Oncologia ed Ematologia, Ospedale Papa Giovanni XXIII, Bergamo, Italy; Division of Hematology and Oncology, Cancer Therapy and Research Center at University of Texas Health Science Center, San Antonio, TX; Drug Development Unit, Florida Cancer Specialists/Sarah Cannon Research Institute, Sarasota, FL; Department of Medicine, Royal Marsden Hospital, Sutton, Surrey, UK; NIHR Clinical Research Facility, The Christie NHS Foundation Trust and University of Manchester, Manchester Academic Health Science Centre, Manchester, UK; Hematology, Hospital Universitario HM Sanchinarro, Madrid, Spain; IRCCS Azienda Ospedaliero-Universitaria di Bologna, Istituto di Ematologia “Seràgnoli”, Bologna, Italy; Dipartimento di Medicina Specialistica, Diagnostica e Sperimentale, Università di Bologna, Bologna, Italy; Department of Hematology and Oncology, Houston Methodist Cancer Center, Houston, TX; Oncology Clinical Science, Takeda Development Center Americas, Inc. (TDCA), Lexington, MA; Servei d’Hematologia, Vall d’Hebron Hospital Universitari, Experimental Hematology, Vall d’Hebron Institute of Oncology (VHIO), Vall d’Hebron Barcelona Hospital Campus, Barcelona, Spain; Departament de Medicina, Universitat Autònoma de Barcelona, Bellaterra, Spain; Current affiliation: Division of Hematology and Oncology, Banner MD Anderson Cancer Center, Gilbert, AZ. DOI - https://doi.org/10.18632/oncotarget.28352 Correspondence to - Leo I. Gordon - l-gordon@northwestern.edu Abstract We report an updated analysis from a phase I study of the spleen tyrosine kinase (SYK) and FMS-like tyrosine kinase 3 inhibitor mivavotinib, presenting data for the overall cohort of lymphoma patients, and the subgroup of patients with diffuse large B-cell lymphoma (DLBCL; including an expanded cohort not included in the initial report). Patients with relapsed/refractory lymphoma for which no standard treatment was available received mivavotinib 60–120 mg once daily in 28-day cycles until disease progression/unacceptable toxicity. A total of 124 patients with lymphoma, including 89 with DLBCL, were enrolled. Overall response rates (ORR) in response-evaluable patients were 45% (43/95) and 38% (26/69), respectively. Median duration of response was 28.1 months overall and not reached in DLBCL responders. In subgroups with DLBCL of germinal center B-cell (GCB) and non-GCB origin, ORR was 28% (11/40) and 58% (7/12), respectively. Median progression free survival was 2.0 and 1.6 months in the lymphoma and DLBCL cohorts, respectively. Grade ≥3 treatment-emergent adverse events occurred in 96% of all lymphoma patients, many of which were limited to asymptomatic laboratory abnormalities; the most common were increased amylase (29%), neutropenia (27%), and hypophosphatemia (26%). These findings support SYK as a potential therapeutic target for the treatment of patients with B-cell lymphomas, including DLBCL. Trial registration: ClinicalTrials.gov number: NCT02000934. Sign up for free Altmetric alerts about this article - https://oncotarget.altmetric.com/details/email_updates?id=10.18632%2Foncotarget.28352 Keywords - Non-Hodgkin’s lymphoma, DLBCL, relapsed/refractory, SYK inhibitor, TAK-659 About Oncotarget Oncotarget is a primarily oncology-focused, peer-reviewed, open access journal. Papers are published continuously within yearly volumes in their final and complete form, and then quickly released to Pubmed. On September 15, 2022, Oncotarget was accepted again for indexing by MEDLINE. Oncotarget is now indexed by Medline/PubMed and PMC/PubMed. To learn more about Oncotarget, please visit https://www.oncotarget.com and connect with us: SoundCloud - https://soundcloud.com/oncotarget Facebook - https://www.facebook.com/Oncotarget/ Twitter - https://twitter.com/oncotarget Instagram - https://www.instagram.com/oncotargetjrnl/ YouTube - https://www.youtube.com/OncotargetYouTube LinkedIn - https://www.linkedin.com/company/oncotarget Pinterest - https://www.pinterest.com/oncotarget/ Reddit - https://www.reddit.com/user/Oncotarget/ Media Contact MEDIA@IMPACTJOURNALS.COM 18009220957

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