Chhabra, S

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.

7508 Background: Data on response to BCMA-targeted therapies among BCMA-exposed pts with RRMM are limited. Outcomes after sequential/subsequent anti-BCMA bispecific T-cell engagers (Bs-TCE) are vital to evaluate. Etentamig is a next-generation differentiated BCMA x CD3 Bs-TCE composed of a bivalent BCMA-binding domain with a high-avidity, low-affinity CD3-binding domain potentially reducing cytokine release syndrome (CRS), and a silenced Fc tail for extended half-life and convenient monthly (Q4W) dosing. Phase 1 results of etentamig in RRMM showed robust efficacy and potential best-in-class safety. Methods: Arm B of the open-label, Phase 1b MOVISO study (NCT05650632) evaluated etentamig in pts with RRMM with ≥2 prior lines of therapy (PLT), including triple-class and prior BCMA exposure (antibody-drug conjugate [ADC] >30 days or CAR-T >6 months [mo] after last exposure). Primary safety endpoints were CRS and immune effector cell-associated neurotoxicity syndrome (ICANS); efficacy endpoints included objective response rate (ORR; IMWG 2016), duration of response (DoR), and progression-free survival (PFS). Pts received etentamig (60 mg IV; no step-up dosing [SUD]) on Cycle 1 Day 1 and Q4W thereafter. Results: At cutoff (June 11, 2025), 41 prior BCMA-exposed pts (CAR-T, n=24; ADC, n=17) had been treated; 24 (57%) were male, 38 (93%) were White, median (mdn) (range) age was 68 (43–89) years, 37 (88%) had ECOG PS ≤1, and 34 (81%) were triple-class refractory. Mdn (range) PLT was 6 (3–15). For 21 (51%) pts, the last PLT was BCMA directed; 23 (56%) had previously responded to anti-BCMA therapy (17/24 [71%] for CAR-T and 6/17 [35%] for ADC). Mdn (range) time from last prior CAR-T or ADC to first dose of etentamig was 15 (1–30) and 4 (1–45) mo, respectively. Mdn (range) follow-up was 5.5 (0.2–17.1) mo. Despite no SUD, CRS and ICANS were reported in 24 (57%) and 3 (7%) pts, respectively; all G1/2 events, except 1 G3 ICANS. G3/4 neutropenia and infections were reported in 15 (36%) and 17 (41%) pts, respectively. Efficacy outcomes are detailed in the Table (NE, not estimable). For pts whose last PLT was BCMA directed, MRD negativity (clonoSEQ, 10 –5 ) was seen in 2/3 (67%) evaluable pts, along with robust peak activation and proliferation of CD8+ T cells. Conclusions: Pts treated with etentamig achieved durable responses; rates were higher in pts who received CAR-T as last line. No new safety signals were observed; only low-grade CRS was seen despite no SUD. Clinical trial information: NCT05650632 . All prior BCMA (N=41) Prior BCMA CAR-T (N=24) ORR, n/n (%) [95% CI] Overall 17/36 (47) [30–65] 11/22 (50) [28–72] BCMA-directed last PLT 11/19 (58) [34–80] 7/11 (64) [31–89] Mdn DoR, mo [95% CI], No. of pts Overall 13 [7–NE], N=17 13 [7–NE], N=11 BCMA-directed last PLT 13 [7–NE], N=11 13 [7–NE], N=7 Mdn PFS, mo [95% CI], No. of pts Overall 3.4 [3–11], N=41 8.3 [2–NE], N=24 BCMA-directed last PLT 9.4 [2–NE], N=21 9.4 [2–NE], N=12