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AbstractBackgroundLate‐Onset Alzheimer’s Disease (LOAD) is characterized by genetic heterogeneity and there is no single model explaining the genetic mode of inheritance. To date, more than 70 genetic loci associated with AD have been identified but they explain only a small proportion of AD heritability. Structural variants (SVs) may explain some of the missing AD heritability, and specifically, their segregation in AD families has yet to be investigated.MethodWe analyzed WGS data from 197 NHW families (926 subjects, 58.5% affected) and 214 CH families (1,340 subjects, 59.17% affected). Manta, Absinthe, and MELT were used for large insertions/deletions calling from short‐read WGS, combined with Sniffles2 calls from 4 ONT‐sequenced genomes and an external SV call set from HGSVC on 32 PacBio‐sequenced genomes from the 1000 Genomes Project. Genotyping produced a unified project‐level VCF. We identified 45,251 insertions and 76,566 deletions genome‐wide. Variants were tested for segregation and pathogenicity using Annot‐SV, cadd‐SV, and Variant Effect Predictor. Segregation required SV presence in all affected family members and only in unaffected members five years younger than average disease onset.ResultWe identified 453 insertions and 598 deletions segregating in 78.68% and 87.31% of NHW families, respectively. In CH families, 432 insertions and 460 deletions were segregating in 75.23% and 72.90% of the families, respectively. Genes overlapping with the SVs exhibited high expression levels in brain tissues. Notably, around 93% of insertions and 76% of deletions segregating in NHW and CH families were less than 1 kilobase pair (1kbp) in length. A total of 79 insertions and 96 deletions were found to be segregating in both NHW and CH families. Interestingly, a segregating insertion was observed in CH families overlapping within the CACNA2D3 gene, which was previously reported in a CH GWAS for clinical AD. A deletion segregating in NHW overlapped with the PSEN1, and another in a CH family overlapped with the PTK2B gene.ConclusionOur findings suggested that there are several SVs associated with familial AD across CH and NHW families. Prioritizing the SVs based on their effects on gene function and expression will be helpful in understanding their contributions in AD.

Importance Monoclonal antibodies (mAbs) targeting calcitonin gene-related peptide (CGRP) or its receptor (anti-CGRP mAbs) offer effective migraine-specific preventive treatment. However, concerns exist about their potential cardiovascular risks due to CGRP blockade. Objective To compare the incidence of cardiovascular disease (CVD) between Medicare beneficiaries with migraine who initiated anti-CGRP-mAbs vs onabotulinumtoxinA in the US. Design, Setting, and Participants This retrospective, sequential cohort study was conducted among a nationally representative population-based sample of Medicare claims from May 2018 through December 2020. Data analysis was performed from August to December 2023. This study included fee-for-service Medicare beneficiaries aged 18 years or older with migraine who initiated either anti-CGRP mAbs or onabotulinumtoxinA. Beneficiaries who had a history of myocardial infarction (MI), stroke, cluster headache, malignant cancer, or hospice service within a 1-year baseline period prior to treatment initiation were excluded. To minimize channeling bias from new drug introductions and time-related bias due to the COVID-19 pandemic, 5 cohorts were established, representing sequential 6-month calendar intervals based on the initial prescription or date of index anti-CGRP mAbs or onabotulinumtoxinA use. Exposure Anti-CGRP mAbs vs onabotulinumtoxinA. Main Outcomes and Measures The primary outcome was time to first MI or stroke. Secondary outcomes included hypertensive crisis, peripheral revascularization, and Raynaud phenomenon. The inverse probability of treatment-weighted Cox proportional hazards models were used to compare outcomes between the 2 treatment groups. Results Among 266 848 eligible patients with migraine, 5153 patients initiated anti-CGRP mAbs (mean [SD] age, 57.8 [14.0] years; 4308 female patients [83.6%]) and 4000 patients initiated onabotulinumtoxinA (mean [SD] age, 61.9 [13.7] years; 3353 female patients [83.8%]). Use of anti-CGRP mAbs was not associated with an increased risk of composite CVD events (adjusted hazard ratio [aHR], 0.88; 95% CI, 0.44-1.77), hypertensive crisis (aHR, 0.46; 95% CI, 0.14-1.55), peripheral revascularization (aHR, 1.50; 95% CI, 0.48-4.73), or Raynaud phenomenon (aHR, 0.75; 95% CI, 0.45-1.24) compared with onabotulinumtoxinA. Subgroup analyses by age group and presence of established non-MI or stroke CVD showed similar findings. Conclusions and Relevance In this cohort study, despite initial concerns regarding the cardiovascular effects of CGRP blockade, anti-CGRP mAbs were not associated with an increased risk of CVD compared with onabotulinumtoxinA among adult Medicare beneficiaries with migraine, who were predominantly older adults or individuals with disability. Future studies with longer follow-up periods and in other populations are needed to confirm these findings.

Background: The direct anterior approach (DAA) is a popular approach for primary total hip arthroplasty (THA). However, the contemporary outcomes for DAA THA need further elucidation. Therefore, we aimed to describe implant survivorship, complications, and clinical outcomes after DAA THA. Methods: From our multi-institutional total joint registry, 3,184 patients who had undergone 3,698 primary DAA THA between 2010 and 2019 were identified. The identified patients had a mean age of 65 years and a mean body mass index (BMI) of 29 kg/m 2 , and 53% of patients were female. The indications for revision and reoperation and the incidence of complications were collected and analyzed. Potential risk factors, including age, sex, BMI, and high-volume compared with low-volume operating surgeons, were examined. Descriptive statistics and Kaplan-Meier survivorship with Cox regression analyses were performed. Results: At 10 years following primary DAA THA, the cohort had 96% (95% confidence interval [CI], 95% to 98%) survivorship free of any revision and 94% (95% CI, 92% to 96%) survivorship free of any reoperation. The leading indications for revision were periprosthetic joint infection (PJI) (n = 24; 5-year cumulative incidence, 0.93% [95% CI, 0.6% to 1.5%]), periprosthetic fracture (n = 20; 5-year cumulative incidence, 0.62% [95% CI, 0.4% to 1.0%]), and aseptic loosening (n = 14; 11 femoral, 3 acetabular; 5-year cumulative incidence, 0.84% [95% CI, 0.5% to 1.5%]). A BMI of ≥40 kg/m 2 was found to be significantly associated with PJI (hazard ratio [HR], 6.4; p < 0.001), reoperation (HR, 3.5; p < 0.001), and nonoperative complications (HR, 2.3; p = 0.018). Survivorship free of recurrent instability was 99.6% (95% CI, 99.4% to 99.8%) at 5 and 10 years, and the cumulative incidence of revision for instability was 0.14% at 5 years. Conclusions: In one of the largest published series to date, survivorship following DAA THA was satisfactory at early to intermediate follow-up. The leading indications for revision were PJI, periprosthetic fracture, and aseptic loosening. Instability after DAA THA was uncommon and infrequently led to revision. As a note of caution, a BMI of ≥40 kg/m 2 was identified as a risk factor for adverse outcome after DAA THA. Level of Evidence: Therapeutic Level IV . See Instructions for Authors for a complete description of levels of evidence.

ABSTRACT Objective To estimate the incidence, prevalence, patient characteristics and healthcare utilization patterns of moderate to severe thyroid eye disease (TED) in the United States. Design Retrospective review of medical and prescription claims data from the Inovalon deidentified claims database. Patients Patients with moderate to severe TED were identified based on specific and sensitive definitions using International Classification of Diseases (ICD) codes selected by a group of TED specialists. Results The incident moderate to severe TED population included 3364 and 1730 patients using the sensitive and specific definitions, respectively. After adjusting for age and gender, corresponding incidence rates in the sensitive and specific populations were 8.97 (13.49 in women and 4.27 in men) and 4.37 (6.59 in women and 2.05 in men) per 100,000 person‐years, respectively. The prevalent population included 16,310 and 8018 patients using the sensitive and specific definitions, respectively, corresponding to adjusted prevalence rates of 44.13 (66.00 in women and 21.39 in men) and 20.55 (31.18 in women and 9.50 in men) per 100,000 persons. A preponderance of women was observed, and comorbidity rates were high, with > 40% of prevalent patients experiencing hypertension. Steroids were the most frequently prescribed medication. The impact of teprotumumab was not captured, since this study only included claims data through 2019. Conclusions The estimated incidence and prevalence rates of TED demonstrate the considerable impact of this disease in the United States, making the creation of a specific ICD code imperative for effective healthcare planning and management.

Aims: Alterations of mitochondrial bioenergetics and arginine metabolism are universally present and mechanistically linked to pulmonary arterial hypertension (PAH), but there is little knowledge of arginine metabolism and mitochondrial functions across the different pulmonary hypertension (PH) groups. We hypothesize that abnormalities in mitochondrial functions are present across all PH groups and associated with clinical phenotypes. We test the hypothesis in PH patients and healthy controls from the Pulmonary Vascular Disease Phenomics Program cohort, who had comprehensive clinical phenotyping and follow-up for at least 4 years for death or transplant status. Mitochondrial transmembrane potential, superoxide production, and mass were measured by flow cytometry in fresh platelets. Metabolomics analysis was performed on plasma samples. Global arginine bioavailability was calculated as the ratio of arginine/(ornithine+citrulline). Results: Global arginine bioavailability is consistently lower than controls in all PH groups. Although the mitochondrial mass is similar across all PH groups and controls, superoxide production and transmembrane potential vary across groups. Mitochondrial superoxide is higher in group 1 PAH and lowest in group 3 compared with other groups, while transmembrane potential is lower in group 1 PAH than controls or group 3. The alterations in mitochondrial functions of group 1 PAH are associated with changes in fatty acid metabolism. Mitochondrial transmembrane potential in group 1 PAH is associated with transplant-free survival. Conclusion: While alterations in mitochondrial function are found in all PH groups, group 1 PAH has a unique mitochondrial phenotype with greater superoxide and lower transmembrane potential linked to fatty acid metabolism, and clinically to survival. Antioxid. Redox Signal. 42, 361–377.

Introduction: Myeloma response to treatment can be biochemical, pathological, or radiological, with pathological assessments being invasive. Next-generation blood flow (PBF) for assessment of circulating tumor plasma cells (CTCs) has shown promising results as a prognostic in Multiple Myeloma (MM) patients. CTC detection via PBF has a potential to serve as non-invasive method for assessing pathological burden of disease and response to treatment. Comparing CTC responses to the International Myeloma Working Group (IMWG) criteria will further help to understand PBF's utility in predicting response to therapy. Patients and Methods: The study conducted is a retrospective observational study. We included patients with MM treated at Mayo Clinic from 01/01/2011 to 12/31/2019 with CTC records available at the time of best response (BR) to frontline therapy. The CTC values were expressed as the number of plasma cell events per 150,000 Peripheral Blood Mononuclear Cells (CD38, CD138, CD19, CD45, Kappa, Lambda). The CTC levels were compared across all response(IMWG Criteria) groups at BR, and at baseline. The CTC response was expressed as % CTC decrease at BR from baseline. Time-to-event analyses utilized the Kaplan Meier method and Cox-proportional hazards models, with comparisons made using the log-rank test. Results: We identified 621 patients with CTC data at the time of BR to frontline therapy. Of these, 148 (24%) had baseline CTC data from diagnosis. The median age at diagnosis was 62.3 (27.2-83.7). The median follow-up was 66.15 months; the distribution of patients by treatment class is as follows- Alkylator: 0.8%, PI(Proteasome Inhibitor)+Cyclophosphamide: 27.4%, IMid: 12.7%, PI+IMid(Immunomodulator): 55.9%, PI+IMid+antiCD38: 3.2%; 378 patients (78.8%) underwent an autologous transplant. BR to initial therapy was sCR/stringent Complete Response (10, 1.6%), CR (230, 36.9%), VGPR/Very Good Partial Response (224, 36.1%), PR (123, 19.8%), MR/Minimal Response (12, 1.9%), SD/Stable Disease (14, 2.3%), PD/Progressive Disease (8, 1.3%). In the study, 64 patients (10.31%) had detectable CTCs at their BR. The distribution of CTCs across the different response categories was as follows: none (0%) in sCR, 3 patients (1.3%) in CR, 18 patients (8%) in VGPR, 24 patients (19.5%) in PR, 8 patients (66.7%) in MR, 6 patients (42.9%) in SD, and 5 patients (62.5%) in PD. The median CTC counts and their interquartile ranges for these categories showed significant variability: CR had a median of 46 (IQR: 28.5, 923), VGPR had 39.5 (IQR: 15.5, 111.25), PR had 47 (IQR: 22.75, 82.5), MR had 55 (IQR: 28.5, 85), SD had 96.5 (IQR: 22.25, 218.75), and PD had 317 (IQR: 57, 415). This Analysis of Variance (ANOVA) for response-wise distribution of CTC was &lt;0.01. Response was dichotomized as PR and above for sCR, CR, VGPR, PR and less than PR for MR, SD and PD. Median Overall Survival(OS) for PR and above was 127.8 months (vs less than PR 56.7 months, p=0.01). Median OS for CTC+ at BR was 56.7 months (vs 134.8 for CTC negative, p=0.01). On multivariate analysis, presence of CTC at best response (Hazards Ratio = 2.9, n=1.1-2.9), RISS staging at diagnosis (Hazards Ratio = 2.35, n=1.5-3.05), less than PR (Hazards Ratio =1.8, 1.1-2.9) were independent predictors of inferior OS. In patients with data for CTC available at both baseline and at BR to frontline therapy (n=148), 110 had CTC detectable at diagnosis. Among patients in various response categories, a complete disappearance of CTCs was observed in sCR (n=3, 75.0%), CR (n=36, 69.2%), VGPR (n=38, 64.4%), and PR (n=14, 60.9%). CTC responses greater than 90% were noted in VGPR (n=3, 5.1%), PR (n=2, 8.7%), and SD (n=2, 40.0%). No CTC response was reported in sCR (1, 25.0%), CR (16, 30.8%), VGPR (2, 3.4% and 13, 22.0%), PR (3, 13.0% and both 2, 8.7%), SD (1, 20.0% and both 2, 40.0%), MR (1, 50.0%), and PD (1, 33.3% and 1, 50.0%, respectively). The median OS for those with a CTC response was 112.4 months vs 28.2 months for no response. (p=0.01). Conclusion: The presence of CTC at best response is an independent prognostic marker for inferior OS. Depth of response to frontline therapy correspond to a high rate of clearance of CTCs. Presence of CTC at best response provides independent prognostic value beyond the depth of response. A complete clearance of CTC at best response is associated with improved OS. CTC levels have not been corrected for WBC counts and may not be applicable in all settings.

INTRODUCTION Primary plasma cell leukemia (pPCL) is a rare and aggressive form of multiple myeloma (MM) with poor survival outcomes. Fluorescence in situ hybridization (FISH) evaluation is essential for the initial risk stratification in MM, and the presence of multiple high-risk (HR) cytogenetic abnormalities by FISH portends a worse prognosis in MM. We have previously observed that the presence of HR cytogenetic abnormalities by FISH at diagnosis is known to confer a poor overall survival (OS) in patients with pPCL. However, less is known about the cumulative effect of multiple HR cytogenetics abnormalities compared to a single HR cytogenetic abnormality on the OS outcomes of patients with pPCL. AIM To evaluate the prognostic implications of additive HR cytogenetics abnormalities by FISH in patients with pPCL treated with novel agents. METHODS We evaluated patients with newly diagnosed pPCL at the Mayo Clinic Comprehensive Cancer Center from 2014 - 2023 that received induction with novel agent combinations. pPCL was defined as patients meeting the diagnostic criteria for MM with 5% or more circulating plasma cells (cPCs) present on morphologic evaluation of their peripheral blood smear. HR cytogenetics abnormalities by FISH was defined by the presence of any one of the following: 1q gain/amplification, t(4;14), t(14;16), t(14;20), and del(17p). Time to next treatment (TTNT) and OS analysis were performed using the Kaplan-Meier method, and differences were assessed using the log-rank test. Statistical analyses were performed using the SAS biostatistical software JMP 17.0.1 (SAS Institute Inc). RESULTS We included 89 patients with newly diagnosed pPCL who received novel agents as first-line therapy between 2014 to 2023. The median follow-up was 45 months (95% CI: 35 - 65). At diagnosis, the median bone marrow plasma cell content was 80% (Range: 10 - 100), and the median cPC% on the peripheral smear was 21% (range: 5 - 85). There were 51 patients (59%) who had 20% or more cPCs on their peripheral smear. There was a preponderance of pPCL patients who had t(11; 14) as their primary cytogenetic abnormality (43%). The median lines of therapy received were 2 (Range: 1 - 9). There were 12 (13%) patients who received intensive induction therapy containing continuous infusional chemotherapy regimens at the onset of their diagnosis. Of the remaining patients, 35 (45%) were treated with a quadruplet (anti-CD38 antibody, proteasome inhibitor and immunomodulator), 24 (31%) with a triplet (proteasome inhibitor and immunomodulator) and 18 (23%) with a doublet (proteasome inhibitor only). The median OS for all pPCL patients in this cohort was 47 months (95% CI: 37 - 100). However, when stratified by cytogenetic risk, the median OS was 101 months (95% CI: 57 - NR) for those patients without any HR cytogenetic abnormalities (N = 24, 27%) vs. 37 months (95% CI: 22 - 63) for those with one or more HR cytogenetic abnormalities (N = 65, 73%) (P = 0.006). Of the patients with any HR cytogenetic abnormalities, 33 (36%) had one HR cytogenetic abnormalities and 32 (34%) had two or more HR cytogenetic abnormalities. The median OS for patients with one compared to two or more HR cytogenetic abnormalities were 47 (95% CI: 38 - 111), and 22 (95% CI: 17 - 37) months, respectively (P = 0.031). The median TTNT was 22 months (95% CI: 16 - 58) for those patients without any HR cytogenetic abnormalities vs. 16 months (95% CI: 9 - 21) for those with one or more HR cytogenetic abnormalities (P = 0.09). The median TTNT from the time of diagnosis for pPCL patients with one compared to two or more HR cytogenetic abnormalities were 18 (95% CI: 6 - 41) and 16 (95% CI: 10 - 19) months, respectively (p = 0.247). CONCLUSION Patients with pPCL with more than one HR cytogenetic abnormality had an inferior OS compared to those with only one HR cytogenetic abnormality, implicating the additive adverse effects of multiple HR cytogenetics abnormalities. In contrast, patients with pPCL without any HR cytogenetic abnormalities had a relatively long median OS (over 100 months).

Background: Venetoclax (Ven), a BCL2 inhibitor, has shown promising responses in multiple myeloma (MM) patients with t(11;14) and/or BCL2 expression. However, consistent benefit in clinical trials remain elusive. This report evaluates the efficacy and safety of Ven combination therapies, including in the non-t(11;14) subgroup, and examines the impact of secondary cytogenetic abnormalities (SGA) on outcomes. Methods: This retrospective study included multiple myeloma (MM) patients without concurrent AL amyloidosis treated with Ven-based combinations at Mayo Clinic sites from January 2015 to December 2023. FISH data was collected at diagnosis and before venetoclax initiation to assess SGAs. Refractoriness was defined by progression on or within 60 days of stopping treatment. Patients refractory to at least one proteasome inhibitor (PI), immunomodulatory drug (ImiD), and anti-CD38 antibody were considered triple-class refractory (TCR). Ven combinations were grouped as: Daratumumab/CD38 antibody (Dara)-Ven based if received Dara ± other drugs, PI-Ven-based without Dara, Ven-dexamethasone (Ven-d), and other combinations (Ven-Misc). BCL2 expression in patients without t(11;14) was determined by immunohistochemistry (IHC). Progression-free survival (PFS) was calculated from treatment initiation to disease progression or last follow-up. Results: We included 232 patients in this study. The median age at diagnosis of MM was 62 years (range 32-87), and the median age at initiation was 68 years (range 35-89). The median time from diagnosis of MM to initiation of Ven was 55 months (95% CI 28, 89 months), and the median follow-up from initiation of Ven-based treatment was 17.2 months (95% CI: 14, 22). Patients had received a median of 3 lines (IQR 4-6); 65% (n=152) of patients were TCR, 71% (n=163) had received autologous stem cell transplant and 7% (n=16) patients had received prior immune effector therapy prior to initiation of Ven-based therapy. The majority (83%, n=190) of the patients harbored a t(11;14); in the patients without t(11;14), a BCL2 expression by IHC was tested in 18 patients and positive in 17 patients. The most common Ven-based combinations included: Dara-Ven-d (19%, n=44), PI-Ven-d (30.2%, n=70), Ven-d (48.3%, n=112), Ven-misc (2.6%, n=6). The overall response rate for the entire cohort was 57% [64% for t(11;14) and 26% for non t(11;14), p&lt;0.0001]. The median PFS for the entire cohort was 9.5 months (95% CI 8.5,13), and the duration of response was 18 months (95% CI 15.2-23.3). The median PFS was 11.8 months (95% CI 9.5-16.7) for patients harboring a t(11;14) compared to 2.9 months (95% CI 1.8, 8.4) for patients without a t(11;14), p&lt;0.0001. Among the non-t(11;14) cohort with BCL2 expression, the median PFS was 1.8 months (95% CI: 1.2-4.2). Among the 190 patients with t(11;14), 18% (34/190) harbored deletion 17p and 32% (60/193) harbored a 1q gain/amplification (referred hereforth as 1q21+) at initiation of Ven-based therapy. In the cohort of patients with t(11;14), the presence of either del17p or 1q21+ (n=85/190) was associated with a significantly inferior PFS [median PFS 8.2 months (95% CI: 5.5,13)] vs. 15.1 months (95% CI: 11.6, 22), p=0.03. At the last follow-up,42 patients had ongoing treatment with ven-based combination. Most common reasons for discontinuation were progression (77% N=140), adverse effect (12%, n=22), patient/provider preference(9%, n=17); 2% (n=4) patients died without progression (3 infection, 1 unclear). The most commonly utilized maximum dose of venetoclax was 400 mg (42%); 15% (n=35) of patients required a dose reduction, and 23% (n=54) received a ramp-up. Tumor lysis syndrome was not noted in any patient. Infectious complications were noted in 23% (n=52). The estimated median OS from initiation of ven-based Rx was 34 months (95%CI 25-47). The estimated median OS for patients without a t(11;14) was 6.2 months (95% CI: 3.3-11.3) compared to 46 months (31.4-54.1), p&lt;0.0001. In the t(11;14) subgroup, the 18-month OS rate was 79% for patients without 1q21+/del17p vs. 50% for patients with a 1q21+/del17p (p=0.002). Conclusion: Venetoclax-based regimens represent an important treatment option for patients harboring a t(11;14). The PFS in patients with BCL2 expression without t(11;14) was poor suggesting lack of efficacy of venetoclax-based regimens for that subgroup. Presence of concurrent del17p and/or 1q21+ with t(11;14) portends an inferior PFS.

Cytokine release syndrome (CRS) commonly occurs during initiation of bispecific T-cell engaging therapy (BsAbs) for multiple myeloma (MM) (NEJM 2022;387:495, NEJM 2022;387:2232, Nat Med 2023;29:2259). Pre-medications, step-up dosing (SUD), and monitoring minimize high-grade toxicity risk, while protocolized outpatient (OP) management of BsAbs and toxicities could reduce resource utilization and improve patient satisfaction. At Mayo Clinic, SUD, clinical assessment and grade 1 CRS management occurs primarily as an OP for patients with MM receiving BsAbs. This study aims to assess the current OP management practices of BsAbs and related toxicities including patient outcomes, admission rates, and resource utilization. Patients with MM who received SUD from August 23, 2023, to March 29, 2024, were included. Baseline demographics, patient outcomes, and CRS management details are summarized. Resource utilization outcomes included level of care, length of hospital stay (LOS), and high-cost drug administration. 38 patients received MM BsAbs during the study timeframe. 34 patients initiated OP SUD (teclistamab n=17 and talquetamab n= 17). The median age was 71 years, 59% were male, 82% were white, and 88% had Medicare coverage. Median number of prior lines of therapy was 6. There were 317 OP encounters with a median of 10 encounters per patient. Of these, 72% were planned in-person assessments, 5% were unplanned clinic visits for potential toxicity-related symptom assessment, and 20% were phone visits that obviated in-person assessment. 66 of 68 doses of talquetamab (total of 1,628 mg) and 48 of 50 doses of teclistamab (total of 2,048 mg) were administered and billed in the OP setting. 24 patients (71%) that initiated OP SUD developed CRS (grade 1 n=16, grade 2 n=7). Management of the initial CRS event included steroids and acetaminophen, with or without tocilizumab. 2,600 mg of tocilizumab administered in the OP setting. Recurrent CRS was seen in 5 patients and also treated entirely OP. 4 patients developed ICANS (grade 1 n=3, grade 3 n=1). Hospitalization following OP SUD initiation occurred in 18 (53%) patients at some point during treatment. Indications included grade 2 CRS (n=6), ICANS (grade 1 n=3), refractory CRS (n=7), infection (n=1), GI bleed (n=1), planned observation for comorbidities or prior CRS (n=2), loss of caregiver (n=1), atrial fibrillation (n=1), heart failure (n=1), and pain crisis (n=1). Median LOS was 2 days. Recurrent admission occurred in 41% and median LOS was also 2 days for subsequent admissions. Two patients were admitted to the intensive care unit for hypotension or arrhythmia. 1 patient required dialysis. In total for SUD during the study time frame, 51 mg of teclistamab, 176 mg of talquetamab, and 8,240 mg of tocilizumab were billed under an IP encounter, which likely was due to inpatient administration or hospital admission within 72 hours of receiving the OP SUD. This descriptive study of our OP BsAb management practice demonstrated that 47% of patients remained OP, even with a CRS event. The CRS rate did not surpass those in landmark clinical trials and aligns with real-world data previously reported (Blood Cancer J 2024;14:35.). Availability and use of patient monitoring capabilities along with lack of sentinel outcomes emphasizes the safety of an OP BsAb practice. Drivers of financial burdens and savings include location and reimbursement of high-cost drugs and admission rates. Median LOS was less than half of what's anticipated with inpatient SUD. Inpatient administration of high-cost drugs can be more costly compared to OP due to associated medical costs and insufficient reimbursement in a population primarily insured by Medicare which reimburses inpatient mediations based on the Diagnostic Related Group (DRG) unless the medication has New Technology Add on Payment (NTAP). Using expected Medicare reimbursement rates and wholesale acquisition costs while excluding variable DRG reimbursement and NTAP impacts for teclistamab, the total net revenue improvement for shifting use of all teclistamab, talquetamab, and tocilizumab OP is $115,004 for the period analyzed (CMS.gov 2024). In conclusion, OP management of patients undergoing SUD for MM BsAbs is safe and has substantial reductions in resource utilization and costs.