Post–CAR T-Cell Monitoring Optimization Improves Access and Safety for Patients With B-Cell Malignancies

CD19-directed CAR T-cell therapy has significantly improved outcomes for patients with relapsed or refractory B-cell malignancies, but the unique toxicities of these treatments—namely cytokine release syndrome (CRS) and immune effector cell–associated neurotoxicity syndrome (ICANS)—require intensive post-infusion monitoring, according to Manali Kamdar, MD. Current recommendations mandate that patients remain within 30 miles of their treating academic center for 4 weeks.

At the 2025 ASCO Annual Meeting, Kamdar, an associate professor of medicine in the Division of Hematology and clinical director of Lymphoma Services at the University of Colorado Anschutz Medical Campus in Aurora, joined OncLive® for an interview to discuss findings from new analyses of lisocabtagene maraleucel (liso-cel; Breyanzi) in patients with B-cell malignancies, reporting on CRS and ICANS timing in 1579 patients treated across clinical trials and the standard-of-care setting to inform safety monitoring requirements.

Liso-cel has received FDA approval in multiple settings, including relapsed/refractory diffuse large B-cell lymphoma (DLBCL), follicular lymphoma (FL), chronic lymphocytic leukemia (CLL), small lymphocytic lymphoma (SLL), and mantle cell lymphoma (MCL). Findings from the CRS and ICANS analysis of this agent incorporated data from five pivotal trials—the phase 1 TRANSCEND NHL 001 trial (NCT02631044), the phase 1/2 TRANSCEND CLL 004 trial (NCT03331198), the phase 3 TRANSFORM trial (NCT03575351), the phase 2 TRANSCEND PILOT 017006 trial (NCT03483103), and the phase 2 TRANSCEND FL trial (NCT04245839)—as well as real-world outcomes captured in the CIBMTR registry.

Across both trial and registry populations, liso-cel demonstrated a predictable safety profile, with most CRS and ICANS effects occurring within 15 days of infusion. In the pooled clinical trial cohort (n = 702), 60% of patients experienced no CRS or neurotoxicity, and among those who did, 96% of events presented within 15 days. Late-onset events were rare, generally low grade, and resolved with treatment. In the CIBMTR registry cohort (n = 877), 53% of patients experienced no CRS or ICANS, and 96% of adverse effects occurred within the first 15 days. Only a small number of patients developed CRS or ICANS beyond day 15, with most effects being grade 1 or 2, though 2 patients experienced grade 3 or higher effects.

“Given the expanded indications of [liso-cel], it is important to figure out [whether] these mandated 4-week [monitoring] requirements [are] a must, [and to] figure out the timing and the management strategies of these unique AEs [with] CAR T-cell therapy,” Kamdar explained in the interview.

OncLive: What was the rationale for examining approaches to optimize post–CAR T-cell monitoring in this study?

Kamdar: CD19-directed CAR T-cell therapy has revolutionized outcomes in [patients with] B-cell malignancies [who] achieve durable remissions. However, irrespective of the CAR T-cell therapy construct, as a function of how [this class of therapy] works, we have to manage unique AEs [associated with] CD19-directed CAR T-cell therapy, namely CRS and ICANS. Usually, these are manageable.

However, as a result of these unique AEs, it’s mandated that the treating site [require] patients [to] remain within 30 miles of the academic treating center for a period of 4 weeks. This [requirement] poses lots of logistical [and] socioeconomic challenges that may impair CAR T- [cell therapy] access.

Liso-cel, one of the CD19-directed CAR T-cell therapy products, [has] shown [efficacy with durable remissions and a manageable safety profile]. It’s now FDA approved in patients with relapsed/refractory DLBCL, relapsed/refractory follicular lymphoma, CLL, [and] SLL, as well as relapsed/refractory MCL. Personalizing the optimization of the post-infusion CAR T-cell therapies [could] hopefully [result in] shorter times where the patients have to remain at the academic center, and thus improve access to care.

What was the design of the study, and how did it integrate data from other pivotal clinical trials and the CIBMTR registry?

This was a comprehensive analysis of 1579 patients [with data] extracted from 5 pivotal [liso-cel] studies, as well as from the CIBMTR registry, which [is] the one real-world dataset where [liso-cel] was explored in relapsed/refractory DLBCL. The 5 pivotal clinical studies [included] patients who received [liso-cel] in relapsed/refractory follicular [lymphoma], MCL, CLL, [and] relapsed/refractory DLBCL.

[In the clinical trials], CRS was defined based on the clinical trial criteria for [liso-cel] across the pivotal studies, [and] the same went for ICANS. On the other hand, in the CIBMTR registry, [CRS and ICANS were defined] based on the Lee criteria and the ASTCT criteria, [respectively].

What were the key findings from this analysis?

Between the 2 datasets, the [patient] characteristics were similar. However, the clinical trial patients were younger and fitter compared with the CIBMTR registry [patients]. [With regard to] refractory disease or the need for bridging therapy, [rates were] equal across the 2 datasets.

Regarding CRS rates, focusing only on clinical trial data, 54% of patients had any-[grade] CRS, and 98% of these events happened within the first 15 days after infusion. Only 7 patients with CRS were identified [as having onset] after the [15-day] infusion window. In the CIBMTR registry, similarly, 50% of patients had any-[grade] CRS, with 97% of patients having CRS within the first 15 days after infusion. Late-onset CRS was rare. [For] the few [patients] who did have late-onset CRS, the grade was low, it was manageable, and patients did not require intensive care unit [ICU]–level care.

Regarding ICANS rates, in the clinical trial dataset, 31% of patients had any-grade ICANS. [The] majority of events, 88%, [occurred] within the first 15 days after infusion. In the CIBMTR registry dataset, 27% of patients had ICANS within the first 15 days after infusion, and 97% of these [events occurred] within the first 15 days after receiving infusion. With regards to late-onset ICANS, [this was again] rare, manageable, and did not require ICU-level care.

Overall, if you combine the 5 pivotal studies and the 1 real-world CIBMTR registry dataset for [liso-cel] across all relapsed/refractory lymphomas that [liso-cel] has [current] approvals for, it is clear that [most CRS and ICANS events] occurred within the first 15 days after [liso-cel] infusion.

This calls for rethinking around the mandated 4-week requirement for patients to be [monitored at] the treating site, and hopefully this will allow personalized [tailoring] of monitoring and [optimization of] patient monitoring requirements after infusion of [liso-cel]. The idea is to improve access and treat patients [with] CAR T-cell therapy across all socioeconomic [and] logistical barriers.

What are the next steps in clinical practice to further optimize monitoring, patient education, and management strategies for CRS and ICANS associated with liso-cel?

This calls for a concerted effort around making sure that these data are out there so the regulatory bodies can review and further optimize the requirement around the 4-week window, and hopefully shorten it to at least 2 and a half weeks. [Doing so would] allow [patients] to return home [following infusion and] make sure the safety [of the therapy] is not compromised.

Reference

Kamdar MK, Shadman M, Ahmed S, et al. Optimizing post–chimeric antigen receptor (CAR) T cell monitoring: evidence across lisocabtagene maraleucel (liso-cel) pivotal clinical trials and real-world experience. J. Clin. Oncol. 2025;43(16_suppl):7026-7026. doi:10.1200/jco.2025.43.16_suppl.7026