Abstracts Clinical Lymphoma, Myeloma & Leukemia September 2023 S424 Esraa Jamal MSc1, Ayesha Ali MSc9, Amy A. Kirkwood MSc10, Sabine Pomplun MD8, Teresa Marafioti PhD8, Maria Calaminici PhD1, Paul Greaves MB, BS11, Sridhar Chaganti PhD6, Pam McKay MB ChB5, Jeffery Smith MBChB12, Toby A. Eyre MBChB4, Nicolas Martinez-Calle PhD3, Kate Cwynarski PhD2, Christopher P. Fox PhD13, Jessica Okosun PhD1 1Centre for Haemato-Oncology, Barts Cancer Institute, Queen Mary University of London, London, United Kingdom. 2Department of Clinical Haematology, University College London Hospital, London, United Kingdom. 3Nottingham University Hospitals NHS Trust, Nottingham, United Kingdom. 4Oxford University Hospitals NHS Foundation Trust, Churchill Cancer Centre, Oxford, United Kingdom. 5Beatson West of Scotland Cancer Centre, Glasgow, United Kingdom. 6Centre for Clinical Haematology, University Hospital Birmingham NHS Foundation Trust, Birmingham, United Kingdom. 7Department of Haemato-Oncology, St Bartholomew’s Hospital, Barts Health NHS Trust, London, United Kingdom. 8Department of Histopathology, University College London Hospital, London, United Kingdom. 9Cancer Research UK Clinical Trials Unit, University of Birmingham, Birmingham, United Kingdom. 10Cancer Research UK and UCL Cancer Trial Centre, Cancer Institute, University College London, London, United Kingdom. 11Department of Haematology, Barking Havering and Redbridge University Hospital NHS Trust, London, United Kingdom. 12Clatterbridge Cancer Centre, Liverpool University Hospitals, Liverpool, United Kingdom. 13School of Medicine, University of Nottingham, Nottingham, United Kingdom Context: Primary central nervous system lymphoma (PCNSL) is a rare B-cell lymphoma with an aggressive course. Although double expressor (DE) status (co-expression of both MYC and BCL2) is a well-established marker of aggressive disease in systemic de novo diffuse large B cell lymphoma (DLBCL), its prognostic impact in PCNSL has been understudied. Objective: To evaluate the prognostic value of DE status in a retrospective cohort of treated PCNSL patients. Design: We performed a retrospective analysis on histologically-confirmed PCNSL patients diagnosed consecutively between 1st May 2015 and 31st May 2020. Treatment with a highdose methotrexate-based chemotherapy regimen was a mandatory inclusion criterion. BCL2 and MYC immunohistochemistry (IHC) data were collated from local diagnostic histology reports, and DE status was defined as per WHO criteria (MYC: surface expression > 40%; BCL2: >50% of cells). Measured outcomes included progression-free (PFS) and overall survival (OS). Results: Data for 242 patients were analyzed. The median age was 65 years (IQR, 5671), and 64% of patients had an ECOG performance status (PS) of 0-1. One hundred and seventy-four (72%) patients received MATRix chemotherapy. DE status was evaluable in 169/242 (69%) patients. DE status was absent due to missing IHC expression data (BCL2: n=28; MYC: n=44) or IHC not reported in line with WHO criteria (BCL2: n=45; MYC: n=7). In the DE-evaluable cohort (n=169), 40% of patients had DE-PCNSL. At a median followup of 1.7 years, 34% of patients relapsed and 45% died. DE status was associated with significantly shorter PFS (median 0.86 years vs 2.77 years; HR 1.61 (1.07 – 2.41); P=.021). This association was maintained in a multivariable analysis modeling age, baseline PS, treatment received, ASCT consolidation status, and DE status (HR 1.75 (1.15 – 2.66); P<.01). There was no significant interaction between induction treatment and DE status (P=.66) indicating that patients with DE have inferior outcomes regardless of induction treatment received. Conclusions: In this large, retrospective cohort of PCNSL patients, double expression of MYC and BCL2 was associated with inferior PFS, even in intensively treated patients. Correlative analyses, including genomic profiling and spatial transcriptomics of DE and non-DE PCNSL tumors, are ongoing to delineate the biological mechanisms underpinning this association. Keywords: PCNSL, primary CNS Lymphoma, double expressor, MYC, BCL2 ABCL-187 Phase 2 Response‑Adapted Study of Ibrutinib With Temozolomide, Etoposide, Liposomal Doxorubicin, Dexamethasone, Rituximab (TEDDI‑R) for Secondary CNS Lymphoma Jillian Simard MD1, James D Phelan PhD1, Christopher Melani MD1, Rahul Lakhotia MBBS1, Stefania Pittaluga MD, PhD2, Jagan R Muppidi MD, PhD1, Michail S Lionakis MD, ScD3, Cody Peer PhD4, Amynah Pradhan NP1, Matthias Holdhoff MD, PhD5, Lode J Swinnen MBChB, MD6, Kieron Dunleavy MD7, Catherine Lai MD, MPH8, Sami Ibrahimi MD9, Michael Glantz MD, PhD10, John A Butman MD, PhD11, Kim Johnson RN1, Seth M Steinberg PhD12, William D Figg PharmD4, Elaine S Jaffe MD2, Louis M Staudt MD, PhD1, Wyndham H Wilson MD, PhD1, Mark Roschewski MD1 1Lymphoid Malignancies Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA. 2Laboratory of Pathology, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA. 3Laboratory of Clinical Immunology and Microbiology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA. 4Clinical Pharmacology Program, Office of the Clinical Director, Center for Cancer Research, National Cancer Institute, Bethesda, MD, USA. 5Department of Neuro-Oncology, The Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins, Baltimore, MD, USA. 6Department of Oncology, The Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins, Baltimore, MD, USA. 7Lombardi Comprehensive Cancer Center, Georgetown University, Washington, DC, USA. 8Abramson Cancer Center, University of Pennsylvania, Philadelphia, PA, USA. 9Stephenson Cancer Center, University of Oklahoma, Oklahoma City, OK, USA. 10Department of Neurosurgery, Penn State College of Medicine, Hershey Medical Center, Hershey, PA, USA. 11Radiology and Imaging Sciences, Clinical Center, National Institutes of Health, Bethesda, MD, USA. 12Biostatistics and Data Management Section, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA Background: TEDDI-R treatment achieves durable remissions in refractory primary central nervous system lymphoma (PCNSL). However, the molecular profile of SCNSL tumors with BCR
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