Real-World Comparison of Lisocabtagene Maraleucel (Liso-Cel) and Axicabtagene Ciloleucel (Axi-Cel): Efficacy & Toxicity

• Published in: Transplantation and cellular therapy Vol. 30; no. 2; p. S192
• Main Authors: Portuguese, Andrew J., Albittar, Aya, Huang, Jennifer J., Liang, Emily C., Wuliji, Natalie, Taheri, Mahnoosh, Hirayama, Alexandre V, Kimble, Erik L., Iovino, Lorenzo, Poh, Christina, Gopal, Ajay K, Shadman, Mazyar, Till, Brian G, Kiem, Hans-Peter, Milano, Filippo, Chapuis, Aude G., Otegbeye, Folashade, Cassaday, Ryan D., Maloney, David G., Gauthier, Jordan
• Format: Journal Article
• Language: English
• Published: Elsevier Inc 01.02.2024
• DOI: 10.1016/j.jtct.2023.12.249
• ISSN: 2666-6367

CD19 CAR-T therapy has revolutionized the management of high risk & relapsed/refractory (R/R) large B-cell lymphoma (LBCL) but remains limited by significant toxicities. In the absence of head-to-head randomized clinical trial data, we evaluated the impact of CAR-T product type on the outcomes of LBCL patients (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 & 6/2023 were included. Best response was determined within 3 months of CAR-T infusion by PET-CT imaging (Lugano 2014 criteria). CRS & ICANS were graded using ASTCT criteria. Pts with measurable disease before &/or after CAR-T infusion were deemed response evaluable. Of 129 total pts, 37% (n=48) & 63% (n=81) received liso-cel & axi-cel, respectively. Seven pts received out-of-specification liso-cel. Liso-cel recipients were older (median 67 vs 62 years, p=.003). Other baseline characteristics were similar (Table). The 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). In response-evaluable pts (liso-cel, n=41; axi-cel, n=79), we observed comparable efficacy with liso-cel vs axi-cel: ORR, 80% vs 77% (p=.7); CR, 56% vs 52% (p=.9). After a median follow-up of 18.2 months, we observed comparable 1-year outcomes with liso-cel vs axi-cel: DOR, 53% vs 60% (p=.6); PFS, 44% vs 46% (p=.82; Fig 1); & OS, 70% vs 60% (p=.4; Fig 2). Liso-cel was associated with lower rates of any grade CRS & ICANS compared to axi-cel: CRS, 62% vs 88% (p=.001); ICANS, 32% vs 56% (p=.010). For liso-cel vs axi-cel, grade 3-4 toxicity (CRS, 23% vs 19% [p=.2]; ICANS, 23% vs 19% [p=.5]) & infectious complications (bacteremia, 6% vs 9% [p=.7]; CMV viremia, 13% vs 6.2% [p=.3]) were similar. Post-infusion cytopenias were less severe after liso-cel: median ANC, 0.32 vs 0.04 x 10³/µL (p<.001); Plt, 69 vs 35 x 10³/µL (p=.003); & Hgb, 8.9 vs 8.2 g/dL (p<.001). Fewer pts had severe neutropenia after liso-cel: 72% vs 93% (p=0.002). In multivariable analysis including pre-LD LDH & ALC, largest lesion diameter, age & HCT-CI score, we could not detect an independent impact of the product type on CR (p=.4; Fig 3), PFS (p>.9), or OS (p=.11). However, axi-cel was independently associated with higher odds of any grade CRS (aOR 4.56, 95% CI 1.65-13.5, p=.004) & ICANS (aOR 3.44, 95% CI 1.42-8.85, p=.008). Our analysis of CD19 CAR-T therapy for R/R LBCL showed similar rates of durable responses following liso-cel & axi-cel in the non-trial setting. Pts who received liso-cel were older, with otherwise comparable baseline characteristics. Liso-cel led to less toxicity & shorter inpt duration, but its vein-to-vein time was longer. We conclude that liso-cel is an appropriate alternative to axi-cel in older and/or frail pts.