INSIGHT: A baseline laboratory profile independently predicts outcomes and demonstrates superiority of lisocabtagene maraleucel (liso-cel) over standard of care (SOC) in second-line (2L) large B-cell lymphoma (LBCL) regardless of baseline profile
Year: 2025
Type: conference-abstract
Abstract: Introduction: CD19-directed CAR T cell therapies have transformed the treatment of patients with R/R LBCL, but the field is still defining those patients most likely to experience durable efficacy and have a low-risk safety profile. Here, we present INSIGHT, a framework based on unsupervised clustering routine clinical laboratory tests at screening that identifies 2 patient profiles: PRIME and STANDARD. These profiles provide a data-driven context for understanding projected efficacy and safety outcomes for patients receiving liso-cel, empowering more tailored treatment decisions for patients with LBCL. Methods: INSIGHT clinical profiles, PRIME and STANDARD, were defined by unsupervised consensus k-means clustering of common clinical laboratory test results at screening (complete blood count with differential, LDH, metabolic panel/electrolytes, and liver and kidney function markers) from clinical trial data in adults with LBCL treated with CAR T cell therapy or immunochemotherapy; cohorts included TRANSCEND NHL 001 (3L+, NCT02631044), TRANSFORM (2L HSCT eligible, NCT03575351), PILOT (2L HSCT ineligible, NCT03483103), and ROBUST (1L, NCT02285062) (n = 1024; liso-cel, n = 384; immunochemotherapy, n = 640). Progression-free survival (PFS) was compared using Kaplan–Meier analysis, log-rank testing, and multivariable Cox models that included sum of the product of perpendicular diameters (SPD) to confirm independence from radiographic tumor burden. Incidences of CRS werecompared using a chi-square test. Results: Across all treatment lines and modalities, PRIME patients (n = 715) had superior PFS compared to STANDARD patients (n = 309) (hazard ratio [HR], 0.62; P< 10⁻⁴), independent of SPD (HR, 0.57; P< 0.001). PRIME patients receiving liso-cel also had lower incidence of CRS versus STANDARD patients (grade ≥ 2: 11% versus 22%, P = 0.01; grade ≥ 3: 1% versus 3%, P = 0.39). Furthermore, the proportion of PRIME patients increased from 58% in 3L+ to 77% in 2L LBCL. In TRANSFORM (2L LBCL), INSIGHT profiles stratified PFS within the SOC arm (HR, 0.33; P = 0.002) but not the liso-cel arm (HR, 0.77; P = 0.51), reflecting the broad benefit of liso-cel in 2L LBCL. Indeed, STANDARD patients treated with liso-cel had longer median PFS compared with PRIME patients treated with SOC (14.8 versus 6.5 months). From screening to infusion, 77% of STANDARD patients transitioned to PRIME profiles; this subgroup achieved similar median PFS compared to patients who were PRIME throughout (P = 0.27), suggesting a window for pre-infusion optimization. Conclusions: INSIGHT's stratification of patients with LBCL across treatment lines and modalities suggests these profiles capture prognostic information. By using readily available laboratory tests at screening, it provides an opportunity to fine-tune patient management before CAR T cell therapy infusion. PRIME patients had a high likelihood of achieving durable response and a lower risk of having grade ≥ 2 CRS, making them potentially ideal candidates for outpatient CAR T cell therapy administration and monitoring. Importantly, both PRIME and STANDARD patients derived greater benefit from liso-cel than from SOC in 2L, underscoring the advantage of early CAR T cell therapy intervention. Integration of INSIGHT into clinical practice could improve access to CD19-directed CAR T cell therapy and optimize the overall clinical management of patients with LBCL.
Source: Blood
Authors: Sahar Ansari, Manali Kamdar, Eniko Papp, Mazyar Shadman, Jeremy Abramson, Begüm D. Topçuoglu, Pei Yang, Lara Stepan, Pradipta Ray, Amanda Przespolewski, Krishna R. Juluri, Eric Bleickardt, Debasmita Roy, Alessandro Crotta, Timothy B. Campbell, Julie A. Rytlewski, Abood Okal, Ethan Thompson, Leanne Peiser
Language: English
Topic: CAR-T cell therapy research
Subfield: Oncology
Field: Medicine
Domain: Health Sciences
Open Access status: bronze
OpenAlex ID: W7108458089