Optimizing post–chimeric antigen receptor (CAR) T cell monitoring: Evidence across lisocabtagene maraleucel (liso-cel) pivotal clinical trials and real-world experience.

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.