Abdallah, Nadine

7543 Background: Delayed neurotoxicity (DNT) after ciltacabtagene autoleucel (cilta-cel) is associated with severe morbidity and mortality occurring in 10-15% of patients. A high post-infusion peak absolute lymphocyte count (ALCpeak ≥3x10 9 /L; ALC hi ) is correlated with an increased risk of DNT (25-30%). We previously examined prophylactic dexamethasone (PPX DEX) administered for 3 days when ALC hi was reached and found no reduction in ALC expansion, DNT incidence or severity. Here, we report the use of prophylactic cyclophosphamide (PPX CTX) on ALC kinetics and DNT. Methods: We conducted a retrospective analysis of patients (pts) treated with cilta-cel at Mayo Clinic (09-12/2025; n =60). Pts with ALC hi received CTX 500 mg IV/PO once (n = 22). Outcomes and ALC kinetics including ALCpeak, ALC D28 (ALC D28 ), and area under the curve D1-D28 (ALC AUC ) were compared with PPX DEX cohort (12/2024-08/2025; n =50) and a historical cohort without PPX (04/2022-11/2024; n =116). Results: Pre-lymphodepletion (LD) demographics were similar across historical ALC hi , PPX DEX, and PPX CTX groups. Pre-LD CRP was higher in the historical ALC hi cohort; however, baseline ferritin, CRS, and ICANS, and disease burden did not differ significantly between groups. There were no statistically significant differences in time to ALCpeak or ALC kinetics among the 3 cohorts. Among pts with ALC < 3×10⁹/L treated during the PPX CTX study period, 2 developed cranial nerve palsy (IEC-CNP; 2/38, 5%). Both presented with unilateral facial nerve palsy and were treated with corticosteroids. One pt resolved symptoms by one month, while the second had persistent symptoms at 2 weeks and remains on follow-up. Among ALC hi patients in the PPX CTX cohort, DNT occurred in 4/22 pts (18%), including 1 case of IEC-CNP (5%) and 3 with parkinsonism (IEC-PKS, 14%). Within the PPX CTX cohort, baseline characteristics and post-infusion CRS or laboratory parameters did not differ between patients with and without DNT. Among patients who developed DNT, ALC kinetics were similar across PPX CTX, PPX DEX, and historical cohorts. PPX CTX was well tolerated, with 2 cases of grade 1 nausea reported. The incidence of DNT did not differ significantly between the PPX DEX (14/61, 23%) and PPX CTX (4/22, 18%) cohorts. However, DNT presentations in the PPX CTX cohort appeared milder and were responsive to treatment. Two of three patients (67%) presented with mild symptoms (one with dynamic dysphasia; second with flat affect) that responded to DEX. A third patient presented with typical parkinsonian features (hypomimia, bradykinesia, rigidity) and demonstrated clinical improvement following high-dose CTX. Conclusions: PPX CTX was well tolerated. While it did not significantly impact ALC expansion kinetics or DNT rates, first few cases of IEC-PKS suggest that the presentation may be milder and amenable to less toxic treatment. Larger cohorts are needed to refine optimal prophylactic strategies.

1633 Background: CAR-T cell therapy has transformed outcomes of hematologic malignancies and is poised to expand into solid malignancies. However, broader use of CAR-T remains constrained by the need for timely cytokine release syndrome (CRS) detection. Current episodic monitoring may miss early physiologic changes. Wearable digital health technologies (DHTs), offering continuous monitoring and real-time alerts, could enable earlier CRS detection, further support outpatient delivery, and expand access to CAR-T and potentially other immunotherapies associated with CRS. Methods: This single-center observational study (NCT05018208) enrolled patients receiving FDA-approved CAR-T products in the outpatient setting at Mayo Clinic, Rochester MN. Management of post-CAR-T complications (e.g. CRS) followed the institution’s standard of care. Patients were monitored from day -5 to day +30 post infusion with intermittent remote patient monitoring (SoC) and an arm-worn wearable device for continuous monitoring (DHT). Patients were included in this analysis if DHT data were available for ≥ 5h of data/day or ≥ 2h of data/night on ≥2 days or nights for baseline and ≥1 day or night within 72h prior to CRS, or at least 2h within 4h of CRS onset, or if DHT was available for ≥7 days/nights post infusion with no CRS event. CRS detection time by DHT was defined as the onset of pyrexia or threshold-based deviation from an individual’s baseline pulse distributions. Results: 32 patients were included in this report (median age 64 years, gender 12 F/20 M, diagnoses 18 MM/14 NHL). 25 patients experienced a CRS event, with maximum CRS grades ranging from 1-3 (16 G1, 8 G2, 1 G3). 24/25 patients with CRS required tocilizumab/steroid. Median CRS onset time was 3.4 days (range 0.4-18.4). 12/32 patients had sufficient DHT data (7 CRS, 5 no CRS) for analysis. 5 patients with CRS had a DHT detection time in advance of the SoC by a median of 13h (range 2.8 - 69.2). The DHT prediction of CRS by baseline HR change was earlier than the first episodic fever by a median of 14.5h (range 13-77.5). The remaining 2/7 patients who did not have CRS detected by the DHT had missing DHT data for more than 45h before a treated CRS event. DHT detected CRS in 2/5 patients without CRS according to SoC. One patient had fever caught with intermittent monitoring. The other was treated for neutropenia fever with suspicion of CRS and/or infection. Conclusions: These results offer evidence that continuous DHT can identify CRS events earlier than intermittent monitoring (SoC). Despite limitations related to compliance with wearable device use and data missingness, and variability in clinical management of CRS, we highlight the usability of DHT and its potential for future studies with optimized strategies to address these limitations. Clinical trial information: NCT05018208 .