Optimizing post–chimeric antigen receptor (CAR) T cell monitoring: Evidence across lisocabtagene maraleucel (liso-cel) pivotal clinical trials and real-world experience.
Year: 2025
Type: conference-abstract
Abstract: 7026 Background: CAR T cell therapies have shown remarkable efficacy in B-cell NHL. Here, we report CRS and ICANS timing in 1579 patients (pt) treated with liso-cel in clinical trials across indications or in the standard of care (SOC) setting to inform safety monitoring requirements. Methods: Data from pivotal trials (TRANSCEND NHL 001, TRANSCEND CLL 004, TRANSFORM, PILOT, TRANSCEND FL) included pts treated with liso-cel for R/R LBCL, CLL/SLL, MCL, and FL; data from the Center for International Blood and Marrow Transplant Research (CIBMTR) Registry included pts who received commercial liso-cel for R/R LBCL and had ≥ 1 assessment after infusion. Outcomes were incidence, onset, grade (gr), and duration of CRS and ICANS from pivotal trials and the CIBMTR Registry. Results: Of 702 pts treated with liso-cel in 5 clinical trials, 46% had no CRS, 54% had any-gr CRS (gr ≥ 3 at onset, 1%); 98% of events had onset ≤ 2 wk after infusion and median duration was 5 d (Table). Of 7 pts with CRS onset > Day 15 (gr 1, n = 5; gr 2, n = 2), all resolved. Most (69%) pts had no ICANS, 31% had any-gr ICANS (gr ≥ 3 at onset, 5%); 88% of events had onset ≤ 2 wk after infusion and median duration was 7 d (Table). Of 27 pts with ICANS onset > Day 15 (gr 1, n = 20; gr 2, n = 6; gr 3, n = 1), all resolved except 1 pt with gr 2 leukoencephalopathy. Of 877 liso-cel–treated pts from the CIBMTR Registry, 51% had no CRS, 49% had any-gr CRS (gr ≥ 3, 3%); 97% of events had onset ≤ 2 wk after infusion and median duration was 4 d (Table). Of 15 pts with CRS onset > Day 15 (gr 1, n = 9; gr 2, n = 2; gr 3, n = 1; unknown, n = 3), 13 resolved (missing, n = 2). Most (73%) pts had no ICANS, 27% had any-gr ICANS (gr ≥ 3, 7%). Of 150 pts with reported onset date, 95% had onset ≤ 2 wk after infusion and median duration was 5.5 d. Of 8 pts with ICANS onset > Day 15 (gr 1, n = 5; gr 2, n = 1; gr 4, n = 2), 5 resolved (missing, n = 3). Further characterization/management of CRS/ICANS events will be presented. Conclusions: Data from the liso-cel pivotal clinical trials and SOC setting from the CIBMTR Registry demonstrated that most CRS/ICANS events occurred ≤ 2 wk after infusion and were not severe. For the few pts who experienced onset of CRS/ICANS after Day 15, most events were low grade and resolved. Clinical trial information: NCT02631044 , NCT03331198 , NCT03483103 , NCT03575351 , NCT04245839 . CRS and ICANS in liso-cel–treated pts. Pivotal clinical trials (N = 702) CIBMTR Registry (N = 877) CRS ICANS CRS ICANS Any gr, n (%) 381 (54) 220 (31) 430 (49) a 234 a,b (27) Gr 3/4/5, c n (%) 4 (0.6)/3 (0.4)/0 29 (4)/3 (0.4)/0 4 (0.5)/13 (1)/7 d (0.8) 43 (5)/17 (2)/5 (0.6) Median (range) time to onset, d 5 (1–63) 8 (1–63) 4 (IQR, 3–6) 6 (IQR, 4–9) Median (range) duration from onset, d 5 (1–37) 7 (1–119) 4 (IQR, 2–6) 5.5 (IQR, 2–11) Onset > Day 15, n/N (%) 7/381 (2) 27/220 (12) 15/430 (3) 8/150 (5) a Gr was to be determined for 3 pts; b A total of 150/234 had a reported onset date; c Gr at onset for clinical trials; maximum gr during reporting period for CIBMTR; d Three pts had PD and 1 had ICANS reported as primary cause of death.
Source: Journal of Clinical Oncology
Authors: Manali Kirtikumar Kamdar, Mazyar Shadman, Sairah Ahmed, Jeremy S. Abramson, Miguel-Angel Perales, Nausheen Ahmed, Sayeef Mirza, Iris Isufi, Matthew J. Frigault, Jennifer Leigh Crombie, David Bernard Miklos, Alberto Vasconcelos, Alessandro Crotta, David Bernasconi, Debasmita Roy, Eric W. Bleickardt, Marcelo C. Pasquini, Bradley Hunter, Matthew Alexander Lunning
Institutions: University of Colorado Cancer Center, University of Washington, Fred Hutch Cancer Center, The University of Texas MD Anderson Cancer Center, Harvard University, Massachusetts General Hospital, Memorial Sloan Kettering Cancer Center, University of Kansas Medical Center, Moffitt Cancer Center, Yale University, Dana-Farber Cancer Institute, Stanford University, Bristol-Myers Squibb (Switzerland), Bristol-Myers Squibb (United States), Medical College of Wisconsin, Intermountain Healthcare, LDS Hospital, University of Nebraska Medical Center
Language: English
Topic: CAR-T cell therapy research
Subfield: Oncology
Field: Medicine
Domain: Health Sciences
Open Access status: bronze
OpenAlex ID: W4410820928