Clinical Lymphoma, Myeloma & Leukemia, Vol.21, Suppl.1 - September 2021

Clinical Lymphoma, Myeloma & Leukemia September 2021 S315 Abstracts cases. Autoimmune hemolytic anemia was diagnosed in 9 (32.1%) stage B patients. Partial responses were achieved for 4-6 months after chlorambucil chemotherapy. 16 (19.5%) patients were followed up to fatal outcomes within 3-19 years, including 5 (31.3%) due to the CLL progression and 5 (31.2%) due to secondary tumors. The overall one-, 3- and 5-year survival was 98.0%, 91.2% and 77 .3%, respectively. The one-, 3- and 5-year survival in stage A patients was equal to 100%, 100% and 95. 7 %; in stage B, 96.4%, 84.8% and 55.4%, correspondingly. Co n clusio n s: CLL was diagnosed commonly in males, aged 60- 7 9 years and in stage A. The survival rates depended on a clinical stage and accounted 98.0% at one year and 77 .3% at 5 years. Keywords: chronic lymphocytic leukemia, low-risk, chemotherapy, survival CLL-032 Approach Strategies in the Diagnosis and Evolution of Chronic Lymphocytic Leukemia Aurelian Udristioiu* Titu Maiorescu University of Bucharest, Faculty of Medicine, Romania Co n text: CLL is a neoplasm of mature B-cells that is typically manifested within the peripheral blood. The risk of progression to overt CLL for low-count MBL, however, is unknown, and, to date, no cases of low-count MBL progressing to CLL have been reported. Objecti v e: It was discovered in the last few years that the production of some percentage of mutant p-53 proteins, with the increased stability in type B lymphocytes, leads to the carcinogenesis process. The aim of this study was to apply the sandwich enzyme-linked immunosorbent assay (sandwich ELISA), as screening method in discovery early stagy of CLL with isoform p-53 protein, resisted in the oncologic conventional treatment. D esig n : The monoclonal antibody PAb 240 recognizes an epitope that is structurally hidden in the wild-type conformation of p-53 and becomes exposed by denaturing the p-53 protein or the mutant conformations of p-53, where point mutations in the P-53 gene alter the terminal structure of the p-53 protein. Setti n g: In the context of a heterogeneous malignant disease, such as CLL-B, this simple and inexpensive ELISA method, such as employed in this study, proves useful for identifying patients to be considered as candidates for personalized therapeutic strategies, based on the mutation of the TP- 53 gene and the presence of p-53 isoform protein. Co n clusio n s: The presented research has an impact on the clinical management of patients and requires adequate therapeutic adaptation in a personalized medicine. Personalized treatments will be applied by combining diagnostic tools, immunohistochemistry (IHC), polymerase chain reaction (PCR), single-chain peptide microarray (SSPMa), next-generation sequencing (NGS), knowledge databases and therapeutic drugs. Keywords: chronic lymphocytic leukemia, isoform p-53 protein, ELISA method, P-53 gene CLL-039 Pirtobrutinib (LOXO-305), a Next- Generation, Highly Selective, Non- Covalent BTK Inhibitor in Previously Treated CLL/SLL: Results from the Phase 1/2 BRUIN Study Catherine C. Coombs 1 *, John M. Pagel 2 , Nirav N. Shah 3 , Nicole Lamanna 4 , Ewa Lech-Maranda 5 , Toby A. Eyre 6 , Jennifer A. Woyach 7 , William G Wierda 8 , Chan Y. Cheah 9 , Lindsey Roeker 10 , Manish R. Patel 11 , Bita Fakhri 12 , Minal A. Barve 13 , Constantine S. Tam 14 , David J. Lewis 15 , James N. Gerson 16 , Alvaro Alencar 17 , Justin Taylor 17 , Omar Abdel-Wahab 10 , Paolo Ghia 18 , Stephen J. Schuster 16 , Jessica Chen 19 , Binoj Nair 20 , Donald E. Tsai 20 , Nora C. Ku 20 , Matthew S. Davids 21 , Jennifer R. Brown 21 , Wojciech Jurczak 22 , Anthony R. Mato 10 1 University of North Carolina at Chapel Hill, Chapel Hill, NC, USA, 2 Swedish Cancer Institute, Seattle, WA, USA, 3 Medical College of Wisconsin, Milwaukee, WI, USA, 4 Herbert Irving Comprehensive Cancer Center, Columbia University, New York, NY, USA, 5 Institute of Hematology and Transfusion Medicine, Warsaw, Poland, 6 Oxford University Hospitals NHS Foundation Trust, Churchill Cancer Center, Oxford, UK, 7 The Ohio State University Comprehensive Cancer Center, Columbus, OH, USA, 8 MD Anderson Cancer Center, Houston, TX, USA, 9 Linear Clinical Research and Sir Charles Gairdner Hospital, Perth, Australia, 10 Memorial Sloan Kettering Cancer Center, New York, NY, USA, 11 Florida Cancer Specialists/Sarah Cannon Research Institute, FL, USA, 12 University of California San Francisco, San Francisco, CA, USA, 13 Mary Crowley Cancer Research, Dallas, TX, USA, 14 Peter MacCallum Cancer Center, Royal Melbourne Hospital, and University of Melbourne, Australia, 15 Plymouth Hospitals NHS Trust - Derriford Hospital, Plymouth, England, 16 Lymphoma Program, Abramson Cancer Center, University of Pennsylvania, Philadelphia, PA, USA, 17 University of Miami Miller School of Medicine, Miami, FL, USA, 18 Università Vita-Salute San Raffaele and IRCCS Ospedale San Raffaele, Milan, Italy, 19 Eli Lilly and Company, 20 Loxo Oncology, Inc, a wholly owned subsidiary of Eli Lilly and Co., 21 Dana-Farber Cancer Institute and Harvard Medical School, Boston, MA, USA, 22 Maria Sklodowska-Curie National Institute of Oncology, Warsaw, Poland Co n text: Despite the marked efficacy of covalent BTK inhibitors (BTKi) in CLL/SLL, the development of resistance and discontinuation for adverse events can lead to treatment failure. Low oral bioavailability or short half-life of these agents can lead to suboptimal BTK target coverage and ultimately result in acquired resistance in some patients (pts). Pirtobrutinib (LOXO-305) is a highly selective, non-covalent BTKi that inhibits both WT and C481-mutated BTK with equal, low nM potency. Objecti v e: To evaluate pirtobrutinib safety and efficacy in pts with CLL/ SLL. D esig n : BRUIN is an ongoing multi-center phase 1/2 trial (NCT03 7 40529). Enrollment was initiated 21 March 2019. Setti n g: Global: community hospitals, and academic medical centers. Patie n ts: As of 2 7 September 2020, 323 previously treated

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