Blue, Brandon

7532 Background: BsAbs are highly effective, off-the-shelf T-cell engagers recently approved for relapsed/refractory multiple myeloma (MM) but remain underutilized in real-world settings. In partnership with the Florida Society of Clinical Oncology (FLASCO), a statewide initiative was launched to expand BsAb access through peer-led regional discussions focused on operational barriers, care transitions, and therapy management strategies. This study assessed the real-world impact of these interventions on BsAb utilization in FL. Methods: Multidisciplinary discussion forums were held in 4 FL metropolitan areas (Jan-Apr 2024). We conducted single and controlled interrupted time series (ITS) analyses using IQVIA eLAAD claims data (Apr 2023 - Sep 2025) including adult patients with a diagnosis of MM, evidence of claim activity, and provider state information. Fifth line or later (5L+) status was estimated as 3.3% of MM prevalence (Nikolaou et al.) BsAb utilization (% of MM 5L+ patients receiving a BsAb) was evaluated using segmented regression to estimate pre- and post-intervention trends, excluding the intervention period. We reported BsAb utilization by comparing FL with all other states, between community versus academic settings, and assessing the number of sites administering BsAb. Results: Before the intervention, BsAb utilization among MM 5L+ patients in FL rose from 8.2% (Apr 2023) to 11.2% (Dec 2023) (0.3 pp/mo; p=0.23), compared with a rise from 6.7% to 16.3% (1.3 pp/mo; p<0.0001) across all other states over the same time period. Post-intervention, BsAb utilization in FL increased from 22.8% (May 2024) to 35.9% (Sep 2025), reflecting a 7.0% immediate increase and 0.8 pp/mo sustained growth, exceeding the post-intervention trend observed across all other states (23.5% to 30.3%; 0.5 pp/mo). Overall, although pre-intervention BsAb utilization in FL was lower than all other states, FL demonstrated a 1.2 pp/month higher post-intervention utilization trend (p<0.001; Table). Post-intervention, FL community sites showed a 0.13 pp/mo higher BsAb utilization trend than academic sites, and the number of community sites administrating BsAb increased from 5 to 9, with no change among academic sites. Conclusions: This study suggests that the FLASCO-led, collaborative model increased BsAb utilization in FL community oncology sites and offers a framework for broader community adoption across other states. Parameter estimates from ITS model(s). FL (%) p-value Other US States (%) p-value Difference CITS:FL - Other US States (%) p-value Intercept (Apr 2023) 8.6 <.0001 7.7 <.0001 0.9 0.52 Monthly change pre-intervention 0.3 0.23 1.3 <.0001 -0.9 0.002 (Apr - Dec 2023) Immediate change post-intervention 7 0.01 0.2 0.87 6.8 0.01 (May 2024) Monthly change post-intervention 0.8 <.0001 0.5 <.0001 1.2 0.0003 (May 2024 – Sep 2025)

Abstract Introduction AL amyloidosis is a rare disorder caused by amyloid fibrils produced by clonal plasma cells, leading to serious organ dysfunction. Cardiac involvement is a major risk factor for poor survival. CD38-binding Daratumumab (D) targets plasma cells and, with bortezomib, cyclophosphamide and dexamethasone (VCd) is the only approved regimen for newly diagnosed AL amyloidosis. The ANDROMEDA phase 3 study showed significant improvements in hematologic responses, major organ deterioration progression free survival and overall survival, compared with VCd alone. The AQUARIUS study (NCT05250973) evaluated cardiac safety of different D-VCd schedules and potential cardiac toxicity mitigation strategies. Methods This multicenter, open-label, phase 2 study enrolled 151 newly diagnosed AL amyloidosis patients at 37 sites in 10 countries. Patients enrolled in either Cohort 1 (n=120, cardiac involvement [Mayo 2004 stage II/IIIA], randomized 2:1 to receive D + immediate VCd or D + deferred VCd) or Cohort 2 (n=31, racial or ethnic minorities with ≥1 any organ involvement, treated with D + immediate VCd). Immediate VCd began on Cycle 1, deferred VCd on Cycle 4. The primary safety endpoint was the incidence of cardiac treatment emergent adverse events (TEAEs). Cardiac assessments included HS TroponinT, NT-proBNP, echocardiogram (ECHO), ECG, NYHA, and the 6-minute walk test (6MWT). Clinical cardiac signs and symptoms (S&S) were assessed at baseline and monthly. Selected, clinically relevant grade ≥3 and/or serious cardiac TEAEs were defined as Major Cardiac TEAE and were assessed by an independent adjudication committee for causality. Patients were followed for 12 treatment cycles or 12 months from first dose (if treatment discontinued prior to 12 cycles). Results 142 patients from both cohorts had cardiac involvement and received at least one dose of D + immediate VCd (n=103) or D + deferred VCd (n=39). Baseline characteristics were balanced between the two groups, including Mayo 2004 stage (IIIa: immediate VCd, 35.0%; deferred VCd, 35.9%; II: immediate VCd, 62.1%; deferred VCd, 53.8%). Treatment duration (median: 10.4 months) and proportion completing ≥10 cycles (79% vs 85%) were similar. Serious cardiac TEAEs occurred at similar rates across groups (immediate VCd, 7.8%; deferred VCd, 7.7%). The most common serious cardiac TEAE (MedDRA term) was cardiac failure (immediate VCd, 5.8%; deferred VCd, 2.6%). Two deaths occurred within 60 days of first study treatment, both were in the immediate VCd group, cardiac-related and unrelated to treatment. The immediate VCd group had fewer cardiac TEAEs overall (48.5% vs 61.5%) but experienced them more frequently during Cycles 1-3 than deferred VCd (35.9% vs 28.2%). This trend reversed for Cycles 4-6 (immediate VCd, 17.7%; deferred VCd, 28.9%). Cardiac TEAEs were low for both groups for Cycles 7-9 (immediate VCd, 9.3%; deferred VCd, 12.1%) and Cycles 10-12 (immediate VCd, 7.4%; deferred VCd, 12.1%). Levels of NT-proBNP, HS troponin T, the 6MWT, and overall cardiac S&S improved similarly for both treatment groups. Rate of cardiac TEAEs of any grade was similar for Mayo stage III patients in the two groups (immediate VCd, 73.0%; deferred VCd, 68.8%) whereas for Mayo stage II patients the incidence was higher in the deferred group (35.9% vs 57.1%). Twenty patients (Immediate VCd, 13; deferred VCd, 7) experienced 30 Major Cardiac TEAEs (selected grade ≥3 and/or serious). Adjudicators attributed 28 events primarily to amyloid cardiomyopathy and 2 events primarily to treatment. These 20 patients had higher baseline Mayo stage (IIIa: 70% vs 29.5%) than the remaining patients (n=122), higher baseline median NT-proBNP (4862 ng/L vs 1723 ng/L) and overall S&S score (7.5 vs 4.0). Several ECHO measures were worse at baseline in these 20 patients (notably, median GLS: -8.8% vs -13.7% and E prime lateral: 4.4 cm/s vs 6.1 cm/s) as was 6MWT (median distance: 319 m vs 363 m). Complete Response (CR) rates were similar in both groups: immediate VCd, 62.1%; deferred VCd, 59.0%. Median time to CR was 64 days for the immediate VCd group and 113 days for the deferred VCd group. Conclusion The D-VCd regimen (immediate or deferred) had a manageable safety profile consistent with previous studies. Cardiac TEAEs were similar between regimens, and their emergence correlated with the start of VCd. Major cardiac events were associated with underlying disease and baseline risk factors that are quantifiable and monitorable.

Abstract Introduction: Teclistamab is the first FDA approved BCMA-directed bispecific antibody for the treatment of relapsed and refractory multiple myeloma (RRMM). With BCMA-targeting CAR-T therapies, cytokine release syndrome (CRS) is a risk factor for cardiotoxicity. Teclistamab was associated with fatal cardiovascular adverse events (CVAEs) in a recent US pharmacovigilance database analysis, but this analysis was limited by reporting bias. Therefore, the aim of our study is to conduct a multicenter study to define the real-world incidence of CVAEs in RRMM patients treated with teclistamab. Method We performed a retrospective multi-center cohort study of patients receiving teclistamab at 5 medical centers. Baseline oncologic and cardiovascular characteristics (including vital sign and echocardiographic data) were collected. Baseline cardiovascular disease (CVD) was defined as presence of coronary artery disease, congestive heart failure, severe or symptomatic valvular heart disease, or stroke at baseline. CVAE was collected and categorized based on CTCAE v5.0 by each institution. Major adverse cardiovascular event (MACE) was a composite outcome with any of the following: congestive heart failure, asymptomatic cardiomyopathy (interval LVEF drop &gt;10% to resultant LVEF less than 50%), coronary artery disease requiring intervention, stroke or cardiovascular death. Arrhythmia was a composite outcome with any of the following: atrial tachyarrhythmia, ventricular tachyarrhythmia or bradyarrhythmia. Median follow-up was calculated through reverse Kaplan-Meier method. Multivariable Cox regression analysis was used to define the relation between MACE and survival. Cause of death was categorized as myeloma-related death or non-myeloma-related deaths (i.e. CRS, infection or cardiovascular death). Cause-specific Cox regression was performed to define relationship between MACE and cause of death. Results In a cohort of 219 patients treated with teclistamab with median follow-up of 20.1 months, 7.3% (N=16) developed MACE, 7.3% (N=16) developed arrhythmia and 12.8% (N=28) developing any MACE or arrhythmia. MACE occurred at a median of 4.5 days (IQR 2.25-15.75 days) after teclistamab step-up. The incidence of MACE was 16.4% in patients with baseline CVD versus 2.7% in those without baseline CVD (p&lt;0.001). Patients who developed MACE had inferior ECOG performance status (PS) (PS &gt;=2: 62.5% vs. 27.7%; p=0.008). Additionally, baseline hemoglobin level (9 vs 10g/dL; p=0.072) was numerically lower in MACE, compared to no MACE. There was no difference in age, sex, bone marrow (BM) plasma cell burden, ferritin, C-reactive protein or LDH levels between MACE vs. no MACE group. Patients who developed MACE had lower baseline diastolic blood pressure (67.7 vs 73.8mmHg; p=0.041) and numerically lower LVEF (51.4 vs 59.3%; p=0.059; baseline echocardiogram performed in 86% of all cohort). Patients who developed MACE had similar incidences of CRS (Grade &gt;=2: 25.0 vs 16.7%; p=0.620) and immune effector cell-associated neurotoxicity (ICANS) grade 2 or higher (12.5 vs 7.5%; p=0.812). In multivariable Cox regression analysis, MACE was independently associated with inferior overall survival (HR 2.72; 95% CI 1.41-5.25; p=0.003), after adjusting for baseline CVD, age, high BM burden, extramedullary disease, and plasma cell leukemia. In cause-specific multivariable Cox regression analysis, MACE was independently associated with non-myeloma-related death (HR: 10.77 95% CI 4.39- 26.41; p&lt;0.001) but not with myeloma-related death (1.54; 95% CI 0.64- 3.70; p=0.336). Conclusion In conclusion, in this large, real-world multicenter study, we observed that MACE occurred in over 7% of patients following teclistamab for RRMM, typically within 2 weeks of initiation. MACE was significantly associated with increased non-myeloma-related mortality. In contrast to CAR-T therapy, CRS or ICANS were not associated with MACE, whereas majority of patients who developed MACE had ECOG PS &gt;=2 or baseline cardiovascular disease. More studies are necessary to define mechanisms and strategies to reduce these MACE and improve survival. Patients with baseline cardiovascular disease or poor performance status may benefit from cardiovascular optimization before and during teclistamab therapy.

Background: Teclistamab (Tec) received regulatory approval for the treatment of relapsed refractory multiple myeloma (RRMM) based on the MajesTEC-1 study. The risk of CRS and ICANS with Tec is well established with a manufacturer's recommendation of inpatient observation for 48-hours for CRS/ICANS monitoring after the initial 3 step up doses. There are limited real-world data on the characteristics of and risk factors for CRS and ICANS with Tec. Such data could inform management of Tec patients (pts), including patient selection for inpatient or outpatient step-up dosing. Methods: RRMM pts treated with standard-of-care Tec across 13 U.S. academic institutions were included in this analysis. The follow-up data cutoff was 30 April 2024. CRS and ICANS classification was based on the American Society for Transplantation and Cellular Therapy consensus grading criteria. Multivariable logistic regression models were fitted to estimate the effects of covariates on CRS and ICANS events, with a particular focus on grade ≥2 CRS, any-grade ICANS, and the combination of CRS grade ≥2 and/or any-grade ICANS. Results: 385 pts were included in the analysis, with a median of 6 lines of prior therapy. Median age was 68 years (range 31-92), 88 patients (25% of pts with available data) had ECOG ≥2, and 301 pts (78%) would have been ineligible for MajesTEC-1. 48 (33%) of 145 evaluable pts with a baseline bone marrow (BM) prior to Tec had &gt;50% BM plasma cells, 139 pts (36%) had extramedullary disease (EMD) (either paraskeletal or true-EMD) and 5 pts (1%) had plasma cell leukemia prior to start of Tec. 224 pts (59%) received Tec with an accelerated step-up dosing regimen, defined as having at least one step-up dose interval of ≥ 2 days. 220 pts (57%) developed any-grade CRS [Grade 1: 46% (N=179), grade 2: 10% (N=37), grade 3: 0.8% (N=3), grade 4: 0.3% (N=1)]. Median time to CRS from start of Tec was 3 days (range, 0-15). Fifty-four pts (14%) developed any-grade ICANS [Grade 1: 7% (N=26), Grade 2: 5% (N=18), grade 3: 3% (N=10), grade 4: none]. There were no grade 5 CRS or ICANS events. Median time to onset of ICANS from start of Tec was 4 days (range, 0-25). There was one case of hemophagocytic lymphohistiocytosis in the entire cohort. 38% of pts received tocilizumab and 17% of pts received corticosteroids. In univariate analysis (UVA), baseline platelet &lt;50, triple-class refractory, penta-refractory status, and EMD prior to start of Tec were associated with increased risk for CRS grade ≥2 (p-values &lt;0.1) and incorporated in MVA. Baseline platelet &lt;50, age &gt;60, ECOG ≥2, Hgb &lt;8 g/dL, BM plasma cells &gt;50%, and ferritin or CRP in the upper quartile were associated with increased risk for any-grade ICANS in UVA (p-values &lt;0.1). Baseline platelet &lt;50, ECOG ≥2, Hgb &lt;8 g/dL, BM plasma cells &gt;50%, ferritin or CRP in the upper quartile, and prior BCMA exposure were associated with increased risk of CRS grade ≥2 and/or any-grade ICANS in UVA (p-values &lt;0.1). Accelerated step-up dosing, renal impairment (CrCl &lt; 30 mL/min) and baseline LDH in the upper quartile were not associated with an increased risk of either CRS or ICANS in UVA. Baseline BM plasma cells &gt;50% was excluded from multivariable analysis (MVA) due to high number of missing data, since most pts (62%) did not undergo BM biopsy prior to start of Tec. In MVA, risk factors for CRS grade ≥2 included baseline platelet &lt;50 at the start of Tec treatment (OR: 2.35, 95% CI 1.08-5.08; p=0.03) and penta-refractory disease (OR: 2.48, 95% CI 1.13-5.45; p=0.02). Risk factors for any-grade ICANS included platelet &lt;50 (OR: 4.18, 95% CI 1.88-9.28; p=0.0004), age &gt;60 (OR: 7.54, 95% CI 1.63-34.89; p=0.01) and CRP in the upper quartile (OR: 2.51, 95% CI 1.16-5.43; p=0.02). Risk factors for CRS grade ≥2 and/or any-grade ICANS included platelet &lt;50 (OR: 2.65, 95% CI 1.42-4.94; p=0.002) and ECOG ≥2 (OR: 2.07, 95% CI 1.19-3.61; p=0.01). Conclusions: This real-world analysis of RRMM pts treated with Tec revealed comparable rates CRS and ICANS relative to the MajesTEC-1 study, and these were mostly limited to grade 1/2. MVA demonstrated a significantly higher risk of CRS grade ≥2 and/or any-grade ICANS in pts with baseline platelet &lt;50 and/or ECOG ≥2, the former may reflect BM disease burden. These results may help identify pts who are at higher risk for IEC related toxicities with Tec that would warrant inpatient monitoring during initial step-up dosing. OP, AA, & LF: co-first authors. AG, HCL & JK: co-senior authors

*Authors contributed equally. Introduction. Two chimeric antigen receptor (CAR) T-cell therapies have been FDA approved for patients with relapsed/refractory multiple myeloma (RRMM): idecabtagene vicleucel (ide-cel) and ciltacabtagene autoleucel (cilta-cel). Prior work from our consortium identified racial and ethnic differences in safety and response to ide-cel among patients treated in the standard of care (SOC) setting; despite these differences, survival was similar across race and ethnicity. Here, we extend this work to investigate racial and ethnic differences in safety, efficacy, and outcomes in a larger cohort of patients treated with SOC ide-cel with longer follow-up and patients treated with SOC cilta-cel. Methods. Data for RRMM patients who underwent leukapheresis by 12/31/2022 and were treated with SOC ide-cel or cilta-cel were pooled across 19 institutions in the U.S. Multiple Myeloma Immunotherapy Consortium. We compared Non-Hispanic White, Non-Hispanic Black, and Hispanic (any race) patients, excluding other racial and ethnic groups due to small sample sizes that precluded sub-group investigations. Separately for each CAR T-cell therapy, racial and ethnic differences in baseline patient characteristics, safety, and treatment responses were examined using chi-square and Kruskal-Wallis rank sum tests. Kaplan-Meier survival curves and log-rank tests were used to examine progression-free survival (PFS) and overall survival (OS) by race and ethnicity. Results. Among 332 RRMM patients treated with ide-cel, Non-Hispanic Black and Hispanic patients comprised 17% and 10% of the cohort, respectively. Hispanic patients were younger at infusion compared to Non-Hispanic Black and Non-Hispanic White patients (55.5 vs. 63 vs. 66 years, p&lt;0.001). Non-Hispanic Black patients had a higher disease burden (≥ 50% bone marrow plasma cell percentage) compared to Non-Hispanic White and Hispanic patients (35% vs. 20% vs. 19%, p=0.05), while a higher proportion of Non-Hispanic White patients had high-risk cytogenetics compared to Non-Hispanic Black and Hispanic patients (37% vs. 23% vs. 10%, p=0.003). Non-Hispanic Black patients were more likely to develop severe (≥ grade 3) cytopenia at day 30 (p&lt;0.001) and day 90 (p=0.01) post-infusion, and these differences were particularly driven by higher rates of severe neutropenia among Non-Hispanic Black patients at these time points. Non-Hispanic White patients were more likely to achieve a best response of partial response (PR) or better (82%) compared to Non-Hispanic Black (75%) and Hispanic patients (63%, p=0.02). No other racial and ethnic differences in baseline patient characteristics (including cytopenias), safety, PFS, and OS were observed (p&gt;0.05). Among 222 RRMM patients treated with cilta-cel, Non-Hispanic Black and Hispanic patients comprised 12% and 9% of the cohort, respectively. At baseline, Non-Hispanic Black and Hispanic patients were more likely to have anemia (p=0.01), and Non-Hispanic Black patients were more likely to have thrombocytopenia (p=0.02) and neutropenia (p=0.06) compared to Non-Hispanic White patients. No other differences in baseline patient characteristics were observed by race and ethnicity. While not statistically significant, a higher rate of severe (≥ grade 3) cytopenia at day 90 post-infusion was observed among Non-Hispanic Black and Hispanic patients compared to Non-Hispanic White patients (33% vs. 44% vs. 21%, p=0.07), similar to the ide-cel cohort. This finding was primarily driven by higher rates of severe neutropenia among Non-Hispanic Black patients and higher rates of anemia among Hispanic patients. No other racial and ethnic differences in safety, responses to cilta-cel, PFS, or OS were not observed in the cilta-cel cohort (p&gt;0.05). Conclusion. In a large cohort of RRMM patients treated with SOC ide-cel or cilta-cel, we observed a higher rate of cytopenias post-infusion and inferior ide-cel responses among racial and ethnic minority patients compared to Non-Hispanic White patients. Despite these differences, survival was similar across race and ethnicity, suggesting that both available CAR T-cell therapies for RRMM patients can be utilized across all populations. Future studies that include larger patient cohorts of racially and ethnically diverse patients should be conducted to confirm these findings and additionally evaluate long-term outcomes.

Abstract Idecabtagene vicleucel (ide-cel) was the first chimeric antigen receptor T-cell therapy to gain US Food and Drug Administration approval for patients with relapsed/refractory multiple myeloma (RRMM). The clinical outcomes of standard of care (SOC) ide-cel in racially and ethnically diverse populations have been understudied. This study pooled data from 207 patients with RRMM (28% patients of racial and ethnic minority groups) treated with SOC ide-cel across 11 institutions to examine racial and ethnic differences in the incidence of toxicities and adverse events, response to ide-cel, and survival. This study included 22 (11%) Hispanic, 36 (17%) non-Hispanic Black, and 149 (72%) non-Hispanic White patients with RRMM. Compared with Hispanic and non-Hispanic White patients, non-Hispanic Black patients had higher median levels of C-reactive protein (1.0, 0.8, and 3.5 mg/dL, respectively; P = .02) and baseline ferritin (362.0 vs 307.0 vs 680.5, respectively; P = .08) and were more likely to develop cytokine release syndrome (77%, 85%, and 97%, respectively; P = .04). Although best overall response rate was lower among Hispanic patients (59%) than among non-Hispanic Black (86%) and White patients (86%; P = .01), there were no racial and ethnic differences in progression-free or overall survival. We provide, to our knowledge, the first and largest investigation of clinical outcomes of SOC ide-cel by race and ethnicity. Despite differences in safety and response to ide-cel, our findings encourage the use of ide-cel in all patients with RRMM. These findings should be confirmed in larger samples of diverse patients with RRMM, with longer follow-up time.

Abstract Introduction: It has been shown that racial/ethnic minorities have worse survival after matched unrelated donor allogeneic hematopoietic cell transplantation(allo-HCT) compared to Whites. Whether the racial disparity in allo-HCT outcomes persists in long-term survivors, and possibly may even be exacerbated in this population that frequently transitions back from the transplant center to their local healthcare providers, is unknown. In the current study we sought to compare long-term outcomes among one-year survivors, by race/ethnicity and socioeconomic status (SES), after allo-HCT reported to the Center for International Blood and Marrow Transplant Research (CIBMTR). Methods: The CIBMTR database was used to identify 5,473 patients with Acute Myeloid Leukemia (AML), Acute Lymphocytic Leukemia (ALL), Chronic Myeloid Leukemia (CML), or Myelodysplastic Syndrome (MDS) who received HCT between 2007-2017, who were alive and in remission for at least 1 year after allo-HCT. Study was restricted to patients transplanted in the United States. Cox regression model was used to determine association of ethnicity/race and SES with overall survival (OS), relapse, and treatment related mortality (TRM). Standardized mortality ratio (SMR) was calculated to compare mortality rates of the study patients to their general population peers matched on race/ethnicity, age and sex. Results: Patients were reported to be Non-Hispanic White (W) (n=4385), Non-Hispanic Black (B) (n=338), Hispanic (H) (n=516), and Asian (A) (n=234). Median follow up after 1 year allo-HCT (months): 69 W, 50 B, 59 H and 57 A (Table 1). Patient neighborhood poverty level was estimated from residential ZIP code at the time of allo-HCT. A ZIP code with ≥20% of persons below the federal poverty level was considered high poverty area. In multivariable analysis, we observed no significant differences in OS, relapse or TRM based on race or poverty level when adjusted for patient-, disease- and transplant-related covariates (Table 2). Conclusions: Our study highlights that among those who survived at least 1-year in remission after allo-HCT, previously reported disparities in post HCT outcomes based on racial/ethnic factors, are not evident in contemporary practice. This might suggest that previously recognized disparity in outcomes could be due to factors that mostly affect patients in their first year post HCT. Future studies are needed to identify these early adverse factors and implement strategies to mitigate them. Figure 1 Figure 1. Disclosures Blue: Janssen Pharmaceuticals: Membership on an entity's Board of Directors or advisory committees; WebMD: Consultancy. Wood: Pfizer: Research Funding; Teladoc: Consultancy; Koneksa Health: Consultancy, Current equity holder in publicly-traded company. Majhail: Incyte Corporation: Consultancy; Anthem, Inc: Consultancy. Saber: Govt. COI: Other.