Abstracts Clinical Lymphoma, Myeloma & Leukemia September 2023 S320 T-lymphocyte and differentiated T-lymphocyte subgroups, as well as functional T-lymphocyte markers such as HLA-DR and PD-1. Keywords: CLL, T-lymphocytes CLL-081 Impact of Multi‑Hit vs Single‑Hit TP53 Mutations in Chronic Lymphocytic Leukemia Steven Hwang MD, Yucai Wang MD, PhD, Kari Rabe MS, Marquise Williams-Watley BS, Paul Hampel MD, Saad Kenderian MB, ChB, Eli Muchtar MD, Amber Koehler PA-C, MS, Amy Behnken APRN, CNP, MS, Neil Kay MD, Sameer Parikh MBBS, Rong He MD, Wei Ding MBBS, PhD Mayo Clinic, Rochester, USA Context: The impact of single-hit vs multi-hit TP53 alterations on treatment outcomes in chronic lymphocytic leukemia (CLL) are understudied. Objective: To compare outcomes between multi-hit vs single-hit TP53 mutation status in CLL patients treated at Mayo Clinic. Methods: Patients with CLL and a TP53 mutation between June 2014-April 2021 were identified. Multi-hit TP53 was defined as presence of multiple TP53 mutations or both TP53 mutation(s) and del17p. Event-free survival (EFS) and overall survival (OS) were calculated from start of treatment post-TP53 mutation detection. Results: Of 145 patients identified, 90 had multi-hit and 55 had single-hit TP53 disruption. Patients with multi-hit and single-hit TP53 disruption had a median EFS of 26.3 months (95% CI 16.6not evaluable [NE]) and 26.4 (95% CI 8.4-NE, P=0.76), respectively, at a median follow-up time of 26.3 months. Patients with multi-hit TP53 disruption had a median OS of 61.8 months (95% CI 47.1NE). Median OS was not reached (95% CI 40.3-NE, P=0.87) in the single-hit cohort. Of 145 patients, 82 had received treatment prior to time of TP53 mutation identification (44 Bruton’s tyrosine kinase inhibitor [BTKi], 38 chemoimmunotherapy [CIT] only). For 44 patients previously treated with BTKi, the median EFS and OS from subsequent treatment initiation (n=28) was 4.6 months (95% CI 2.9-23.7) and 46.0 months (95% CI 13.2-NE), respectively. Patients with single-hit (n=9) and multi-hit (n=19) TP53 alterations had a median EFS of 8.4 months (95% CI 4.2-NE) and 4.6 months (95% CI 2.7-NE, P=0.76), respectively, and a median OS of NE (95% CI 8.4-NE) and 46.0 months (95% CI 13.1-NE, P=0.81), respectively. For 38 patients previously treated with CIT only, the median EFS and OS from subsequent treatment initiation (n=28) was 26.3 months (95% CI 13.5-NE) and 40.6 months (95% CI 27.5-NE), respectively. Patients with single-hit (n=11) and multi-hit (n=17) TP53 alterations had a median EFS of 29.8 months (95% CI 5.4-NE) and 26.3 months (95% CI 16.1-NE, P=0.69), respectively, and a median OS of 40.3 months (95% CI 29.8-NE) and 53.7 months (95% CI 25.6-NE, P=0.52), respectively. Conclusions: Treatment outcomes did not differ significantly between patients with multi-hit versus single-hit TP53 alterations, regardless of prior treatment exposure. Keywords: CLL, TP53 CLL-094 Lisocabtagene Maraleucel (liso‑cel) in R/R Chronic Lymphocytic Leukemia (CLL)/Small Lymphocytic Lymphoma (SLL): Primary Analysis of the Phase 1/2, Single‑Arm, Multicenter TRANSCEND CLL 004 Study Tanya Siddiqi MD1, David G. Maloney MD, PhD2, Saad S. Kenderian MB, ChB3, Danielle M. Brander MD4, Kathleen Dorritie MD5, Jacob Soumerai MD6, Peter A. Riedell MD7, Nirav N. Shah MD8, Rajneesh Nath MD9, Bita Fakhri MPH, MD10, Deborah M. Stephens DO11, Shuo Ma MD, PhD12, Tatyana Feldman MD13, Scott R. Solomon MD14, Stephen J. Schuster MD15, Serena K. Perna MD16, Sherilyn A. Tuazon MD17, San-San Ou MS17, Eniko Papp PhD17, Yizhe Chen PhD16, William Wierda MD, PhD18 1City of Hope National Medical Center, Duarte, USA. 2Fred Hutchinson Cancer Research Center, Seattle, USA. 3Mayo Clinic, Rochester, USA. 4Duke University Health System, Durham, USA. 5UPMC Hillman Cancer Center, University of Pittsburgh, Pittsburgh, USA. 6Center for Lymphoma, Massachusetts General Hospital Cancer Center, Boston, USA. 7The David and Etta Jonas Center for Cellular Therapy, University of Chicago, Chicago, USA. 8Medical College of Wisconsin, Milwaukee, USA. 9Banner MD Anderson Cancer Center, Gilbert, USA. 10University of California San Francisco, San Francisco, USA. 11Huntsman Cancer Institute, University of Utah, Salt Lake City, USA. 12Robert H. Lurie Comprehensive Cancer Center of Northwestern University, Chicago, USA. 13John Theurer Cancer Center at Hackensack Meridian Health, HMH School of Medicine, Hackensack, USA. 14Northside Hospital Cancer Institute, Atlanta, USA. 15University of Pennsylvania, Abramson Cancer Center, Philadelphia, USA. 16Bristol Myers Squibb, Princeton, USA. 17Bristol Myers Squibb, Seattle, USA. 18The University of Texas MD Anderson Cancer Center, Houston, USA Background: We report the primary analysis of TRANSCEND CLL 004 (NCT03331198) evaluating liso-cel in patients with R/R CLL/SLL. Methods: Patients must have received ≥2 prior lines of therapy, including a Bruton tyrosine kinase inhibitor (BTKi). Eligible patients received liso-cel at a target dose level (DL) of either 50 or 100 (DL2) × 106 CAR+ T cells. Primary endpoint was CR and CR with incomplete marrow recovery (CRi) rate by independent review committee per 2018 international workshop on CLL criteria in the prespecified subset of efficacy-evaluable patients with disease progression on BTKi and venetoclax failure (primary efficacy analysis set [PEAS]) at DL2 (null hypothesis [H0]:≤5%). Key secondary endpoints were ORR (H0:≤40%) and rate of undetectable minimal residual disease (uMRD; 10-4) in blood (H0:≤5%). Results: Of 137 leukapheresed patients, 117 received liso-cel (safety set), 96 (DL2=87) were efficacy evaluable, and 53 (DL2=49) were in the PEAS. In the safety set, median age was 65 years, 83% had high-risk features, and median lines of prior therapy was 5 (all had prior BTKi). Median on-study follow-up was 21.1 months. In the PEAS at DL2, CR/CRi rate was met at 18.4% (95% CI, 8.8-32.0; 1-sided P=0.0006). ORR was 42.9% (95% CI, 28.8-
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