Imatinib‐induced complete and long‐term sustained remission in chemotherapy‐resistant systemic ALK‐positive anaplastic large cell lymphoma
نویسندگان
چکیده
Background: Platelet-derived growth factor receptor (PDGFR) is expressed in nucleophosmin–anaplastic lymphoma kinase (NPM-ALK) positive anaplastic large cell lymphomas (ALCL ALK+). Our previous preclinical research suggested that PDGFR blockade by the Abl/c-Kit/PDGFR inhibitor imatinib could be an effective treatment strategy for ALCL ALK+. A young indicator patient whose cells and who failed three lines (including autologous stem transplantation) achieved complete remission (CR) with imatinib. Methods: We report of 6 relapsed/refractory (r/r) ALK-positive patients, 4 which were treated a prospective clinical trial (EudraCT No.: 2013-003505-26). Median follow-up was 40 months (160 weeks, range 4–428). Patients characterized whole exome sequencing, bisulfite immunological prnofiling. Whole sequencing data integrated compared to 25 additional ALK+ patients (Larose et al. Haematologica, 2021). Results: out CR maintained throughout 3.3–8.9 years. 5-year progression-free survival (PFS) 67%. Lymphoma two non-responding did not express PDGFRA/B. Cytoplasmic co-expression both ALK PDGFRA/B tumor associated response patients. Methylation profiling confirmed differentially activated axis between responders non-responders identified specific protein profile included significant upregulation HGFAC, VEGFa, TNFa. Additionally, exclusive mutational signature genes linked vesicular endocytosis signaling as resistance mechanism pan-kinase inhibitors. EA - Encore Abstract: Regional or national meeting (≤1'000 attendees) Keywords: Aggressive T-cell non-Hodgkin lymphoma, Diagnostic Prognostic Biomarkers, Molecular Targeted Therapies No conflicts interests pertinent abstract.
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ژورنال
عنوان ژورنال: Hematological Oncology
سال: 2023
ISSN: ['1099-1069', '0278-0232']
DOI: https://doi.org/10.1002/hon.3164_372