Abstracts Clinical Lymphoma, Myeloma & Leukemia September 2023 S328 controlled trials are required to support that new-generation BTKis for their safety and tolerability. Keywords: CLL, Bruton tyrosine kinase inhibitor, acalabrutinib, zanubrutinib CLL-528 Frequency of NOTCH1 Mutation and Its Correlation With Clinical‑Haematological Features and Treatment Response in Chronic Lymphocytic Leukemia in Sudanese Patients Jameel Saif M.Sc1,2, Sahar G. Elbager PhD2, Fady M.M. Abushaqra M.Sc2, Ebrahem Al-Mehraby M.Sc2, Zainab Shumo M.Sc3, Hanan Mohamed PhD3, Basmat Ekhotam Bsc4, Nahla Hameed M.Sc3, Douaa Sayed MD5 1Amin Nasher Higher Institute for Health Sciences, Aden, Yemen. 2Department of Haematology, Faculty of Medical Laboratory Sciences, University of Medical Sciences and Technology, Khartoum, Sudan. 3Molecular Biology Department, National Public Health Laboratory, Khartoum, Sudan. 4Influenza and Genome Department, Khartoum, Sudan. 5Clinical Pathology Department, Faculty of Medicine, Sues University, Sues, Egypt Background: Chronic lymphocytic leukemia (CLL) is a malignant disease that mostly affects the elderly. The clinical course and presentation are extremely variable, ranging from asymptomatic to active disease that can cause progressive complications. CLL has shown extraordinary variety in genomic and molecular characteristics. NOTCH1 has emerged as the most frequently altered gene in CLL at the time of diagnosis; mutation is linked to poor outcomes and makes treating CLL more challenging. Objective: To determine the frequency of NOTCH1 c.7544-7545 delCT among Sudanese patients with CLL and its correlation with clinical-haematological features and treatment response. Patients and Methods: This was a cross-sectional study conducted in the haematology unit at Khartoum Oncology Hospital, Sudan, from March through December 2022, including 29 CLL patients diagnosed according to the International Workshop on Chronic Lymphocytic Leukemia (IWCLL). NOTCH1 c.7544-7545 delCT mutation was screened for using allele-specific polymerase chain reaction (AS-PCR). Results: The overall mean (SD) age was 59.13 (12.13) years (range, 30–82 years). NOTCH1 c.7544‑7545 delCT mutation was detected in 4 patients (13.8%). The frequency of NOTCH1 mutation was not significantly associated with age or sex (P>0.05 for both). The most frequent clinical finding among patients with the NOTCH1 mutation was lymphadenopathy (100%), followed by splenomegaly (50%) and hepatomegaly (25%). Anaemia and thrombocytopenia were present in 100% and 50% of patients, respectively. The frequency of NOTCH1 mutation was not significantly associated with clinical or haematological features. There was no significant association between clinical stage and NOTCH1 mutations (P=0.861) or treatment response rate (P=0.525) Conclusion: The current study shows that the frequency of NOTCH1 c.7544-7545 delCT mutations is 13.8% in Sudanese CLL patients. The frequency of NOTCH1 mutation does not correlate with age, sex, clinical-haematological features, or treatment response. This needs to be confirmed by further studies. Keywords: CLL, chronic lymphocytic leukemia, NOTCH1, clinical manifestations, hematologic features, response to therapy CLL-542 High Rates of Undetectable Minimal Residual Disease Remissions With Time‑Limited Bendamustine, Rituximab, and Venetoclax (BR‑VR) in Untreated Chronic Lymphocytic Leukemia (CLL) — an Updated Analysis Andrew Lipsky MD1, Brian Hill MD, PhD2, Allison Winter MD2, Joseph Jurcic MD1, Todd Rosenblat MD, MS1, Nicole Lamanna MD1 1Herbert Irving Comprehensive Cancer Center, Columbia University Medical Center, New York, USA. 2Taussig Cancer Center Department of Hematology and Medical Oncology, Taussig Cancer Institute, Cleveland, USA Context: Despite the efficacy of venetoclax (VEN) in frontline CLL, optimal combination regimens and duration of treatment remain unclear. Objective: Our study assesses the efficacy and safety of bendamustine/rituximab induction followed by VEN/rituximab (BR-VR) consolidation for a fixed one-year duration in treatmentnaive CLL patients. We hypothesized this strategy would increase undetectable minimal residual disease (uMRD) rate and reduce tumor lysis syndrome (TLS) risk. Design/Methods: In this phase 2, single-arm, open-label study (NCT03609593), patients ≥18 years requiring therapy received 3 cycles of BR, followed by dose-escalated VEN and 6 cycles of VR, then 5 cycles of VEN alone. The primary endpoint was objective response rate (ORR), with secondary endpoints including uMRD rate, time to uMRD, and adverse events (AEs). Results: As of May 2023, 42 patients were accrued; 24 with ≥15 months follow-up completed therapy. Baseline demographics: median age 61.5 yrs (range 38-84). Prognostic studies: unmutated IGHV in 16 (66%) pts, TP53 aberrant 1 (5%) pt. The ORR was 100% (79% CR/CRi, 21% PR [due to small residual nodes]). After initial BR induction, 18% achieved CR/CRi and 82% achieved PR. At 16 months, uMRD (<0.01%) in peripheral blood (PB) and bone marrow (BM) was 78% and 70.5%, respectively. MRD was intermediate (0.01% - <1.0%) in 23% (4 patients) in BM. Median time to uMRD was 10 mo. (range 2-15) in PB and 12 mo. (range 3.6-15) in BM. The most common treatment-emergent AEs during BR induction were (any grade/grade ≥3) anemia in 13/3 (46%/10%) pts, nausea in 7/0 (25%/0%), neutropenia in 10/6 (36%/21%), and rash in 10/1 (36%/4%). Emergent AEs during VEN treatment included neutropenia in 17/11 (60%/39%), diarrhea in 16/0 (57%/0%) pts, leukopenia in 14/9 (50%/32%), and nausea in 10/0 (36%/0%). TLS risk was substantially reduced after BR lead-in. Of 5 H-risk pts at baseline, 1 remained H-risk after BR; of 12 M-risk pts, only 3 remained M-risk, with the remainder at L-risk. Conclusion: The BR-VR regimen in treatment-naive CLL patients is safe, well-tolerated, and yields high PB and BM uMRD rates across all prognostic risk groups. The strategy substantially reduces TLS risk. Keywords: CLL, MRD, BR, venetoclax, time-limited therapy
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