Real-world evaluation of health care resource utilization, clinical effectiveness, and safety of lisocabtagene maraleucel and axicabtagene ciloleucel administered in the outpatient (OP) setting for R/R large B-cell lymphoma (LBCL)

Abstract Introduction: Use of CD19-directed CAR T cell therapies has transformed treatment of patients with LBCL. OP administration has the potential to improve access, reduce health care resource utilization (HCRU), and lower costs; however, direct real-world data on safety, HCRU, and effectiveness remain limited. This study seeks to address this knowledge gap by evaluating the real-world HCRU and clinical outcomes of lisocabtagene maraleucel (liso-cel) and axicabtagene ciloleucel (axi-cel) in the OP setting for LBCL. Methods: This retrospective study used the US Flatiron Health electronic health record–derived database that included adults (≥18 years) with R/R LBCL who received a first CAR T cell therapy infusion with commercial liso-cel or axi-cel in an OP setting between April 1, 2022, and October 31, 2024. Exclusion criteria included evidence of primary CNS lymphoma and CAR T cell therapy as part of a clinical trial. Primary objectives were to describe CAR T cell therapy–related AEs (cytokine-release syndrome CRS, cytopenia, infections, and immune effector cell-associated neurotoxicity syndrome ICANS), AE management, and HCRU among patients with R/R LBCL treated with liso-cel or axi-cel in an OP setting. Secondary objectives were to describe OS and PFS. Descriptive statistics were used to analyze AEs and HCRU. KM landmark survival analysis was used to estimate OS and PFS. Results: A total of 1278 patients were identified (315 who received liso-cel, 963 who received axi-cel). The analysis included 127 patients treated in the OP setting, of whom, 75 of 315 (23.8%) received liso-cel and 52 of 963 (5.4%) received axi-cel. Baseline and disease characteristics between patients treated with liso-cel and axi-cel were broadly similar. Median (range) age was 67 (26–85) and 66 (24–82) years, the proportion with ECOG PS ≤2 was 70.7% and 69.2%, and the proportion with elevated LDH was 22.7% and 23.1%, respectively. Most patients had DLBCL, not otherwise specified (88.0% and 80.8%, respectively); 32.0% of patients treated with liso-cel and 19.2% of patients treated with axi-cel received treatment in non-NCI–designated community centers. A numerically lower proportion of liso-cel recipients had any-grade CRS (41.3% vs 82.7%), grade ≥3 CRS (0% vs 5.8%), any-grade ICANS (17.3% vs 48.1%), and grade ≥3 ICANS (4.0% vs 13.5%) vs axi-cel. Numerically fewer liso-cel recipients required pharmacologic management of CRS or ICANS. For CRS, tocilizumab and dexamethasone or other steroids, respectively, were used in 18.7% and 8.0% of liso-cel recipients and in 40.4% and 34.6% of axi-cel recipients. For ICANS, tocilizumab and dexamethasone or other steroids, respectively, were used in 2.7% and 6.7% of liso-cel recipients and in 5.8% and 17.3% of axi-cel recipients. At Day 30 after CAR T cell infusion, numerically lower rates of grade ≥3 leukopenia (29.3% vs 40.4%), anemia (13.3% vs 19.2%), and thrombocytopenia (14.7% vs 23.1%) were reported for liso-cel vs axi-cel recipients, whereas rates of neutropenia were similar (32.0% vs 34.6%). The proportions of patients with infections were also similar (24.0% vs 23.1%). Overall, liso-cel recipients experienced numerically lower proportion of hospitalization, shorter stays, and lower proportion of ICU admission. At 3 days after infusion, 21.2% of liso-cel recipients vs 39.6% of axi-cel recipients were hospitalized, with median durations of stay of 9.0 vs 10.0 days, respectively; ICU admissions were 1.5% vs 10.4%, respectively. Similar trends were noted for liso-cel vs axi-cel at 1 month (hospitalization rate: 45.5% vs 62.5%; median duration of stay: 5.0 vs 10.5 days; ICU admissions: 1.5% vs 16.7%) and 3 months after infusion (hospitalization rate: 47.0% vs 64.6%; median duration of stay: 8.0 vs 11.0 days; ICU admissions: 4.5% vs 16.7%). Median follow-up was 10.7 and 12.0 months for liso-cel and axi-cel, respectively. At 12 months after infusion, KM estimates of OS were 81.1% (standard error SE, 5.5%) and 70.9% (SE, 6.9%), and estimates for PFS were 52.3% (SE, 6.8%) and 49.9% (SE, 7.6%), respectively. Conclusions: In this real-world OP cohort, liso-cel appeared to have favorable HCRU and safety and comparable survival outcomes compared with axi-cel. The findings support the feasibility of OP CAR T cell therapy administration as a treatment option for the management of R/R/ LBCL, alleviating the hospital-based burden of patients who receive CAR T cell therapy.