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2131 Lisocabtagene Maraleucel Versus Axicabtagene Ciloleucel: Efficacy and Toxicity in a Real-World Setting

Program: Oral and Poster Abstracts
Session: 705. Cellular Immunotherapies: Late Phase and Commercially Available Therapies: Poster I
Hematology Disease Topics & Pathways:
Research, Clinical Practice (Health Services and Quality), Lymphomas, non-Hodgkin lymphoma, Clinical Research, Diseases, real-world evidence, Lymphoid Malignancies, Adverse Events
Saturday, December 9, 2023, 5:30 PM-7:30 PM

Andrew J Portuguese, MD1, Aya Albittar, MD1*, Emily C Liang, MD1, Jennifer J. Huang, MD, PhD1, Alexandre V Hirayama, MD1*, Erik L Kimble, MD1, Lorenzo Iovino, MD, PhD1, Christina Poh, MD1, Ajay K Gopal, MD1,2, Mazyar Shadman, MD, MPH3, Brian G Till1, Hans-Peter Kiem1, Filippo Milano, MD4, Aude G Chapuis, MD1, Folashade Otegbeye, MBChB, MPH1, Ryan D Cassaday, MD1, David G Maloney, MD, PhD1 and Jordan Gauthier, MD, MSc3

1Fred Hutchinson Cancer Center, Seattle, WA
2Division of Hematology and Oncology, University of Washington, Seattle, WA
3Clinical Research Division, Fred Hutchinson Cancer Center, Seattle, WA
4Translational Science and Therapeutics Division, Fred Hutchinson Cancer Center, Seattle, WA

CD19 CAR-T therapy has revolutionized the management of high-risk and relapsed/refractory (R/R) large B-cell lymphoma (LBCL) but remains limited by significant toxicities leading to morbidity/mortality and high resource utilization. Single-arm studies have suggested differences in efficacy and toxicity across FDA-approved CD19 CAR-T products. A matching-adjusted indirect treatment comparison showed comparable efficacy and more favorable safety with lisocabtagene maraleucel (liso-cel) compared to axicabtagene ciloleucel (axi-cel), but was limited to clinical trial patients (pts) and suffered from an absence of patient-level data (Maloney, J Hematol Oncol, 2021). In the absence of randomized clinical trial data, adjusted comparative analyses using pt-level data are critically needed to guide product choice. Therefore, we retrospectively evaluated the impact of CAR-T product type on the outcomes of 129 LBCL pts receiving liso-cel or axi-cel per standard of care.

All LBCL pts treated at our center with liso-cel or axi-cel outside of a clinical trial between 1/2018 and 5/2023 were included. Best response was determined within 3 months of CAR-T infusion by PET-CT imaging per Lugano 2014 criteria. Cytokine release syndrome (CRS) and immune-effector cell-associated neurotoxicity syndrome (ICANS) were graded using ASTCT criteria.

Of 129 total pts, 37% (n=48) and 63% (n=81) received liso-cel and axi-cel, respectively. Seven pts received out-of-specification liso-cel on an expanded access protocol. Pts who received liso-cel were older (median 67 vs 62 years, p=.003). Other baseline characteristics, including male sex (liso-cel vs axi-cel: 63% vs 69%, p=.4), HCT-CI score (1.0 vs 1.0, p=.6), pre-lymphodepletion (LD) LDH (178 vs 214 U/L, p=.14) and ALC (0.65 vs 0.60 x 10³/µL, p=.3), largest lesion diameter (3.1 vs 3.0 cm, p=.4), and extranodal disease (56% vs 56%, p>.9) were similar. The vein-to-vein time (time from leukapheresis to CAR-T infusion) was longer for liso-cel: median, 35 vs 27 days (p<.001). After liso-cel, the total inpt duration was shorter (median, 5 vs 14 days, p<.001) and fewer pts had ≥2 admissions (8.3% vs 22%, p=0.043). In pts with measurable disease prior to LD (n=113), we observed comparable efficacy with liso-cel vs axi-cel: ORR, 82% vs 77% (p=.5); CR, 56% vs 51% (p=.8). After a median follow-up of 17.7 months, we observed comparable 1-year outcomes with liso-cel vs axi-cel: duration of response (DOR), 56% vs 61% (p=.7); progression-free survival (PFS), 47% vs 47% (p=.99; Figure); and overall survival (OS), 69% vs 60% (p=.39).

In pts evaluable for toxicity assessment (n=129), liso-cel was associated with lower rates of CRS and ICANS compared to axi-cel: any grade CRS, 62% vs 88% (p=.001); ICANS any grade, 32% vs 56% (p=.010); days with fever, median 2 vs 5 days (p<.001). Grade 3-4 CRS, 2.1% vs 9.9% (p=.2) or grade 3-4 ICANS, 23% vs 19% (p=0.5) were similar. We measured lower peak serum inflammatory markers after liso-cel: CRP, 58 vs 114 mg/L (p<.001); ferritin, 622 vs 1,315 ng/mL (p=0.007); IL-6, 55 vs 204 pg/mL (p=.010); and D-dimer, 1.4 vs 2.4 mg/L (p=.017). The incidence of infectious complications after liso-cel vs axi-cel was as follows: bacteremia: 6% vs 9% (p=.7); CMV viremia: 13% vs 6.2% (p=.3). Post-infusion median nadir cytopenias were less severe after liso-cel: ANC, 0.32 vs 0.04 x 10³/µL (p<.001); Plt, 69 vs 35 x 10³/µL (p=.003); and Hgb, 8.9 vs 8.2 g/dL (p<.001). Fewer pts developed severe neutropenia after liso-cel: 72% vs 93% (p=0.002).

In multivariable analysis including pre-LD LDH and ALC, largest lesion diameter, age and HCT-CI score, we could not confirm an independent impact of the product type on CR, PFS, or OS (Table). However, axi-cel remained independently associated with a higher odds of any grade CRS (adjusted OR [aOR] 4.56, 95% CI 1.65-13.5, p=.004) and any grade ICANS (aOR 3.44, 95% CI 1.42-8.85, p=.008).

Our analysis of CD19 CAR-T therapy for R/R LBCL in the non-trial setting showed similar rates of durable responses following liso-cel and axi-cel. Pts who received liso-cel were older, with otherwise comparable baseline characteristics. Although liso-cel was associated with less toxicity, its vein-to-vein time was longer. In multivariable analyses, pre-LD LDH and largest lesion diameter were the only factors independently associated with response outcomes. We conclude that liso-cel is a robust alternative to other CD19 CAR-T products in older and frailer LBCL pts.

Disclosures: Hirayama: Nektar Therapeutics: Honoraria, Research Funding; Juno Therapeutics, a Bristol Myers Squibb Company: Research Funding; Bristol Myers Squibb: Honoraria, Research Funding; Novartis: Honoraria. Kimble: Juno/BMS: Research Funding. Iovino: Mustang Bio: Current equity holder in publicly-traded company. Poh: Incyte: Research Funding; Seattle Genetics: Consultancy; BeiGene: Consultancy; Acrotech: Consultancy. Gopal: Compliment Corporation: Current holder of stock options in a privately-held company; Incyte, Kite, Morphosys/Incyte, ADCT, Acrotech, Merck, Karyopharm, Servier, Beigene, Cellectar, Janssen, SeaGen, Epizyme, I-Mab bio, Gilead, Genentech, Lilly, Caribou, Fresenius-Kabi: Consultancy; Merck, I-Mab bio, IgM Bio, Takeda, Gilead, Astra-Zeneca, Agios, Janssen, BMS, SeaGen, Teva, Genmab: Research Funding. Shadman: Bristol Myers Squibb: Consultancy, Research Funding; Regeneron: Consultancy; ADC therapeutics: Consultancy; MorphoSys/Incyte: Consultancy, Research Funding; Vincerx: Research Funding; Mustang Bio: Consultancy, Research Funding; Fate Therapeutics: Consultancy; Genentech: Consultancy, Research Funding; AstraZeneca: Consultancy, Research Funding; BeiGene: Consultancy, Research Funding; TG Therapeutics: Research Funding; Janssen: Consultancy; MEI Pharma: Consultancy; Kite, a Gilead Company: Consultancy; AbbVie: Consultancy, Research Funding; Pharmacyclics: Consultancy, Research Funding; Eli Lilly: Consultancy; Genmab: Consultancy, Research Funding. Till: Mustang Bio: Consultancy, Patents & Royalties, Research Funding; BMS/Juno Therapeutics: Research Funding; Proteios Technology: Consultancy, Current holder of stock options in a privately-held company. Kiem: Rocket Pharmaceuticals: Consultancy; Ensoma: Consultancy; Homology Medicines: Consultancy; V.O.R. Biopharma: Consultancy; Magenta Therapeutics: Consultancy; CSL Behring: Consultancy. Milano: ExCellThera Inc.: Research Funding. Chapuis: Juno Therapeutics: Research Funding. Cassaday: Merck: Research Funding; Incyte: Research Funding; Kite/Gilead: Consultancy, Honoraria, Research Funding; Amgen: Consultancy, Honoraria, Research Funding; Pfizer: Consultancy, Honoraria, Research Funding; Servier: Research Funding; Vanda Pharmaceuticals: Research Funding; Jazz: Consultancy, Honoraria; Autolus: Membership on an entity's Board of Directors or advisory committees; PeproMene Bio: Membership on an entity's Board of Directors or advisory committees; Seagen: Other: Spouse was employed by and owned stock in Seagen within the last 24 months.. Maloney: Legend Biotech: Consultancy, Honoraria, Research Funding; A2 Biotherapeutics: Consultancy, Current holder of stock options in a privately-held company, Honoraria, Other: Member of the Scientific Advisory Board; Incyte: Consultancy, Honoraria; MorphoSys: Consultancy, Honoraria; Janssen: Consultancy, Honoraria; Kite, a Gilead Sciences: Consultancy, Honoraria, Research Funding; Juno Therapeutics: Consultancy, Honoraria, Patents & Royalties: Rights to royalties from Fred Hutch for patents licensed to Juno Therapeutics/BMS, Research Funding; Genentech: Consultancy, Honoraria, Other: Chair and Member of the Lymphoma Steering Committee; Amgen: Consultancy, Honoraria; Mustang Bio: Consultancy, Honoraria; Celgene: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Participation on a Data Safety Monitory Board , Research Funding; Gilead Sciences: Consultancy, Honoraria, Other: Member, Scientific Review Committee, Research Scholars Program in Hematologic Malignancies; Bristol Myers Squibb: Consultancy, Honoraria, Other: Member of the JCAR017 EAP-001 Safety Review Committee and Member, CLL Strategic Council, Member of the JCAR017-BCM-03 Scientific Steering Committee under BMS, Research Funding; Navan Technologies: Consultancy, Honoraria, Other: Member of the Scientific Advisory Board; Novartis: Consultancy, Honoraria; Pharmacyclics: Consultancy, Honoraria; Umoja: Consultancy, Honoraria; Bioline Rx: Consultancy, Membership on an entity's Board of Directors or advisory committees, Other: Participation on a Data Safety Monitory Board ; Fred Hutch: Other: rights to royalties for patents licensed to Juno; Navan Technologies: Current holder of stock options in a privately-held company; Chimeric Therapeutics: Other: Member of the Scientific Advisory Board; ImmPACT Bio: Other: Member, Clinical Advisory Board, CD19/CD20 bi-specific CAR-T Cell Therapy Program; Interius: Other: Member, Clinical Advisory Board; Lyell Immunopharma: Other: Member, CAR T Steering Committee. Gauthier: Kite Pharma: Consultancy, Honoraria; MorphoSys: Consultancy, Research Funding; Angiocrine Bioscience: Research Funding; Century Therapeutics: Other: Independent data review committee; Janssen: Consultancy, Honoraria; Legend Biotech: Consultancy, Honoraria; Celgene (a Bristol Myers Squibb company): Research Funding; Juno Therapeutics (a Bristol Myers Squibb company): Research Funding; Sobi: Consultancy, Honoraria, Research Funding.

*signifies non-member of ASH