Cellular and T cell engager Immunotherapy

Category: Cellular and T cell engager Immunotherapy

Optimizing Post–Chimeric Antigen Receptor (CAR) T-Cell Monitoring: Evidence Across Idecabtagene Vicleucel (ide-cel) Pivotal Clinical Trials and Real-World Experience

(PA-078) Optimizing Post–Chimeric Antigen Receptor (CAR) T-Cell Monitoring: Evidence Across Idecabtagene Vicleucel (ide-cel) Pivotal Clinical Trials and Real-World Experience

Wednesday, September 17, 2025

Surbhi Sidana, MD

Associate Professor
Stanford University School of Medicine

Introduction:
CAR T-cell therapies, including B-cell maturation antigen–directed ide-cel, have shown remarkable efficacy in relapsed and refractory multiple myeloma (RRMM), though toxicities can occur. Here, we report incidence and timing of cytokine release syndrome (CRS) and neurotoxicity (NT) from clinical trials and real-world experience (RWE) of ide-cel to inform post-infusion safety monitoring requirements.

Methods:   Safety data were analyzed from patients (pts) with RRMM treated with ide-cel in 2 pivotal clinical trials and 1 RW registry. Pooled data from the phase 2 KarMMa (NCT03361748) and phase 3 KarMMa-3 (NCT03651128) trials comprised 349 pts who received ide-cel. RW data comprised 998 pts from the Center for International Blood and Marrow Transplant Research (CIBMTR) registry who had ≥1 assessment after infusion of commercial ide-cel. Safety analyses included incidence, grade (G), onset and duration of CRS and NT after ide-cel infusion.

Results:   Pt characteristics were similar in the clinical trials and registry (median age, 62 y and 66 y; males, 62% and 58%; median prior regimens, 4.0 and 6.0; high-risk cytogenetic abnormalities, 37% and 23% [though 47% not tested/unknown for CIBMTR]).

Clinical trials: CRS occurred in 89% of pts (310/349; G3 at onset, 5.2%; no G4/5). Of those with CRS, 98% (304/310) had first onset ≤1 wk (median, 1 d) after infusion; median time to resolution from onset was 4 d. Of 1.9% (6/310) with CRS onset >1 wk (median, 13 d) after infusion, median time to resolution was 6.5 d. Investigator identified (ii) NT occurred in 40% of pts (139/349; G3 at onset, 1.1%; no G4/5). Of those with iiNT, 81% (112/139) had first onset ≤1 wk (median, 2 d) after infusion; median time to resolution from onset was 3 d. Of 19% (27/139) with iiNT onset >1 wk (median, 24 d) after infusion, median time to resolution was 7 d.

Registry: CRS occurred in 84% of pts (834/998; G≥3 in those with G reported, 3.4%). Of pts with CRS and time to onset data, 96.6% (804/832) had first onset ≤1 wk (median, 2 d) after infusion; median time to resolution was 3 d. Of 3% (28/832) with CRS onset >1 wk (median, 48 d) after infusion, median time to resolution was 2 d. Immune effector cell associated neurotoxicity syndrome (ICANS) occurred in 31% of pts (313/998; G≥3 in those with G reported, 5.7%). Of those with ICANS and time to onset data, 82.7% (201/243) had first onset ≤1 wk (median, 2 d) after infusion; median time to resolution was 4 d. Of 17% (42/243) with ICANS onset >1 wk (median, 16.5 d) after infusion, median time to resolution was 4 d.

Conclusions:

Safety data from 1347 pts across ide-cel pivotal clinical trials and RWE demonstrate most cases of CRS and NT are low grade (G1/2) and occur within 1 wk of ide-cel infusion (median 1-2 d). For the pts with event onset >1 wk post-infusion, median time to resolution from onset was ≤7 d. These findings highlight the manageable safety profile of ide-cel, supporting a flexible monitoring period after 1-wk post–ide-cel infusion for patients with RRMM.