Abstracts Clinical Lymphoma, Myeloma & Leukemia September 2023 S458 achieving EFS24 in patients with MCL. Design: Multicohort study using Mayo/Iowa MER cohort, BC Cancer cohort, and Swedish Lymphoma Register. Two treatment eras were defined for each cohort based on local treatment pattern changes. Main Outcome Measures: Overall survival (OS) compared with age- and sex-matched general population and COD. Results: In the MER cohort, patients treated in Era M1 (2002-2009; n=110) and M2 (2010-2015; n=127) both had inferior OS compared with the general US population. A lower standardized mortality rate (SMR) (2.43 vs 3.95) in Era M2 suggested a narrower gap in OS vs the general population. Lymphoma was the leading COD in both eras. In Era M1, patients achieving EFS24 still had inferior OS compared with the general population (SMR=2.81); lymphoma remained the leading COD. However, in Era M2, patients achieving EFS24 had similar OS compared with the general population (SMR=1.35); lymphoma was no longer the leading COD. In the BC cohort, patients treated in Era B2 (6/2013-2019; n=188) vs Era B1 (2003-5/2013; n= 250) had a narrower gap in OS compared with the British Columbia population (SMR 4.53 vs 6.69). Lymphoma was the leading COD in both eras. For patients achieving EFS24, the gap in OS was narrower in Era B2 vs B1 (SMR 3.56 vs 4.99). After achieving EFS24, lymphoma was the leading COD for patients in Era B1 but not in Era B2. Similar results were seen in the Swedish cohort. The gap in OS compared with the general Swedish population was narrower in Era S2 (20132018; n=439) vs S1 (2006-2012; n=442), both after frontline chemotherapy (SMR 4.8 vs 5.4) and after achieving EFS24 (SMR 2.6 vs 3.4). After achieving EFS24, lymphoma was the leading COD for patients in Era S1 but not in Era S2. Conclusions: In the more recent era, OS after achieving EFS24 improved and moved closer to expected background survival, and lymphoma-related mortality was no longer the leading COD. Keywords: mantle cell lymphoma, event-free survival at 24 months (EFS24), overall survival, cause of death MCL-096 Lisocabtagene Maraleucel (Liso‑Cel) in R/R MCL: Primary Analysis Results From the MCL Cohort of the Single‑Arm, Multicenter, Phase I Seamless Design TRANSCEND NHL 001 Study M. Lia Palomba MD1, Tanya Siddiqi MD, MBBS2, Leo I. Gordon MD3, Manali Kamdar MD, MBBS4, Matthew Lunning DO5, Alexandre V. Hirayama MD6, Jeremy S. Abramson MD, MMSc7, Jon Arnason MD8, Nilanjan Ghosh MD, PhD9, Amitkumar Mehta MD10, Charalambos Andreadis MD, MS11, Scott R. Solomon MD12, Ana Kostic MD13, Christine Dehner BSc13, Ricardo Espinola MD14, Lily Peng MS13, Ken Ogasawara PhD, MPH15, Amy Chattin PhD13, Michael Wang MD16 1Memorial Sloan Kettering Cancer Center, New York, USA. 2City of Hope National Medical Center, Duarte, USA. 3Northwestern University, Feinberg School of Medicine, Robert H. Lurie Comprehensive Cancer Center, Chicago, USA. 4University of Colorado Cancer Center, Aurora, USA. 5University of Nebraska Medical Center, Omaha, USA. 6Fred Hutchinson Cancer Center, Seattle, USA. 7Massachusetts General Hospital Cancer Center, Harvard Medical School, Boston, USA. 8Beth Israel Deaconess Medical Center, Boston, USA. 9Levine Cancer Institute, Atrium Health, Charlotte, USA. 10University of Alabama at Birmingham, Birmingham, USA. 11University of California, San Francisco, San Francisco, USA. 12Northside Hospital Cancer Institute, Atlanta, USA. 13Bristol Myers Squibb, Seattle, USA. 14Bristol Myers Squibb, San Diego, USA. 15Bristol Myers Squibb, Princeton, USA. 16The University of Texas MD Anderson Cancer Center, Houston, USA Introduction: We report primary analysis results from patients with R/R MCL who received liso-cel in TRANSCEND NHL 001 (NCT02631044). Methods: Eligible patients had PET-positive R/R MCL after ≥2 lines of prior therapy, including BTKi, alkylating agent, and CD20-targeted agent. Patients received liso-cel at a target dose level of 50 (DL1) or 100×106 CAR+ T cells (DL2) after lymphodepleting chemotherapy (LDC). Primary endpoints were treatment-emergent AEs (TEAE) and ORR per IRC (Lugano criteria); secondary endpoints included CRR (key), DOR, PFS, and OS. Primary and key secondary efficacy hypothesis testing was hierarchical and based on the primary analysis set (PAS) of patients with PET-positive disease per IRC at baseline (DL2). Safety set included all patients (DL1+DL2). Efficacy set included all patients (DL1+DL2) with PET-positive disease per IRC at baseline. Results: Of 104 leukapheresed patients, 88 received liso-cel (DL1, n=6; DL2, n=82). Median (range) age was 68.5 years (36-86) and prior lines of therapy was 3 (1-11). Patient/disease characteristics included refractory disease (69%), BTKi refractory (53%), Ki67 ≥30% (75%), blastoid morphology (31%), and TP53 mutations (23%). Median (range) on-study follow-up was 16.1 months (0.4-60.5). Primary and key secondary endpoints were met based on the PAS (n=74; ORR, 86.5% [95% CI, 76.5-93.3], P<0.0001; CRR, 74.3% [62.8-83.8], P<0.0001). In the efficacy set (n=83), ORR was 83.1% (73.3-90.5), CRR was 72.3% (61.4-81.6), median (95% CI) DOR was 15.7 months (6.2-24.0) and PFS was 15.3 months (6.6-24.9). Six patients in ongoing CR died due to COVID-19; censoring for COVID-19 deaths resulted in median (95% CI) DOR, 17.5 months (7.6-24.0) and PFS, 17.8 months (7.6-24.9). In the safety set (n=88), 86% had grade ≥3 TEAEs, primarily cytopenias. Anygrade cytokine release syndrome (CRS) incidence was 61% (grade 3/4, 1%; no grade 5) and neurological events (NE) was 31% (grade 3/4, 9%; no grade 5). Incidence of grade ≥3 infections was 15%; prolonged cytopenia was 40%. Four grade 5 TEAEs occurred (3 related to liso-cel and/or LDC). Conclusions: Liso-cel demonstrated high response rates that were durable and was well tolerated, with low incidence of grade ≥3 CRS, NE, and infections in R/R MCL. Keywords: MCL, mantle cell lymphoma, lisocabtagene maraleucel, relapsed or refractory, CAR T-cell therapy, Phase I MCL-153 Ibrutinib Therapy in Relapsed/ Refractory Primary Central Nervous System Lymphomas Serkan Güven MD
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