Wang, Yucai

7062 Background: MCL is a rare and aggressive subtype of B-cell non-Hodgkin lymphoma that remains incurable. Bruton tyrosine kinase (BTK) inhibitors are an established standard of care for R/R MCL. However, comparative effectiveness data for different BTK inhibitors for R/R MCL are limited. This study evaluated the real-world effectiveness of zanu and acala in US patients with R/R MCL based on overall survival (OS) and time to next treatment (TTNT). Methods: A retrospective cohort study was conducted using Komodo health administrative claims data. Eligible patients were adults (aged ≥18 years) with ≥2 MCL diagnoses and continuous enrollment or activities within 1 year prior to and 3 months following the index date. Patients were required to initiate monotherapy with zanu (index period: November 2019 to August 2025) or acala (index period: October 2017 to August 2025) as a second-line or later (2L+) treatment, with index date defined as the first observed claim for zanu or acala. Patients with evidence of clinical trial participation, end stage renal disease or prior stem cell transplant were excluded. Outcomes included OS (time from index date to all-cause mortality) and TTNT (time from index date to subsequent therapy with an allowable gap of 120 days). If an outcome was not observed, patients were censored at the date of last activity or enrollment end date. Survival analyses were conducted using Kaplan-Meier estimates and Cox proportional hazards models. Inverse probability of treatment weighting (IPTW) was adjusted for age, sex, US region, treatment initiation year and Charlson Comorbidity Index (CCI). Results: In total, 2219 patients (zanu, n=931; acala, n=1288) were eligible and included in the study. The mean age was higher in the zanu (72.3 years; SD, 9.4) vs acala cohort (71.4 years; SD, 9.7). Most patients were male (zanu, 71%; acala, 75%), non-Hispanic white (zanu, 73%; acala, 74%), and the mean CCI was 3.5 (SD, 3.2) and 3.6 (SD, 3.1) in the zanu and acala cohorts, respectively. Median follow-up was 14.8 and 18.2 months in zanu and acala cohorts, respectively. Median TTNT was 26.7 months for zanu and 20.8 months for acala. Median OS was not reached for zanu and was 60.6 months for acala. In the unadjusted model, zanu had a longer TTNT (HR, 0.86; 95% CI, 0.76-0.97; P =.012) and OS (HR, 0.74; 95% CI, 0.62-0.88; P <.001). After IPTW adjustment, TTNT and OS favored zanu treatment (TTNT: IPTW-adjusted HR, 0.86; 95% CI, 0.76-0.98; P =.025; OS: IPTW-adjusted HR, 0.81; 95% CI, 0.68-0.98; P =.03). Conclusions: In this real-world analysis of US health claims data, zanu monotherapy demonstrated significantly longer TTNT and improved OS compared with acala in patients receiving 2L+ therapy for MCL. These findings support zanu as an effective BTK inhibitor for R/R MCL.

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 .