Citations

Purpose of the review Perioperative pain management continues to evolve as we see the pendulum of opioid use swinging back from highly restrictive administration towards more balanced intraoperative dosing strategies. Striking the optimal balance between nonopioid multimodal pain regimens and thoughtful opioid use has been at the forefront of cardiac surgical enhanced recovery protocols for several years. Herein, we review the history of methadone as a long-acting opioid and its resurgence with pleiotropic benefits in cardiac surgery patients. Recent findings Despite barriers to use and potential adverse effects, methadone is a proven agent for long-lasting analgesia, potentially reducing both short- and long-term opioid consumption. Multiple studies have demonstrated safety and efficacy in cardiac surgery. Dosing (0.1–0.3 mg/kg) and timing vary slightly in published studies and protocols; however, through standardization and clinical judgement regarding patient selection, methadone can safely be used to reduce opioid use and improve analgesia for cardiac surgery. Summary Further studies are needed to explore the mechanisms and ideal protocols for incorporating methadone into routine use as part of existing enhanced recover protocols. Long-term treatment effects extending beyond the immediate postoperative period, outcomes when included with adjuncts, and broader dose-response analysis are needed to guide future implementation.

Background Cardiovascular disease (CVD) is a leading cause of death in cancer survivors. Predicting CVD risk in this population remains challenging. Risk prediction models that use machine learning algorithms could provide an objective method for accurate risk prediction to facilitate the prevention and management of CVD in cancer survivors. We evaluated previously tested machine learning algorithms and logistic regression (regularized by machine learning methods), in addition to testing and validating newer, more complex machine learning algorithms, for CVD prediction in cancer survivors. Methods This multicenter study used a database of 3835 multiracial cancer survivors with 89 clinical, laboratory, and echocardiographic features over 20 years. Models were trained using repeated random and time‐split samples and tested on a separate cohort of 329 patients. Model performance was assessed using the area under the receiver operating characteristic curve. Results Regularized logistic regression achieved an area under the receiver operating characteristic curve of 0.845 (heart failure), 0.783 (atrial fibrillation), 0.792 (coronary artery disease), and 0.806 (composite CVD). These are comparable to 0.837 and 0.848 for heart failure, using Bayesian additive regression tree and random forest as more advanced machine learning models, respectively. De novo composite CVD (post‐cancer diagnosis) was also predicted with an area under the receiver operating characteristic curve of 0.826 using regularized logistic regression, compared with 0.735 and 0.802 using decision tree and random forest, respectively. Conclusions Regularized logistic regression and advanced machine learning models demonstrated similar predictive performance, with institutional transferability. These tools may support risk stratification and prevention strategies in cardio‐oncology using longitudinal data. Registration URL: https://www.clinicaltrials.gov ; Unique identifier: NCT05377320.

Abstract Objectives The aim of this work was to develop an American Headache Society position statement addressing diagnostic screening for migraine among girls and women. Background Despite its high prevalence and substantial negative impacts, migraine is underdiagnosed and undertreated. Diagnostic screening for migraine enables more patients to receive timely, appropriate, and effective management. Methods Development of this position statement followed the rules established by the American Headache Society Guidelines Committee. The published literature was reviewed to determine if migraine meets criteria for when disease screening is justified, to guide recommendations for screening tools, and to determine subpopulation(s) for which migraine screening is indicated. After author consensus was reached, the position statement was reviewed and approved by the American Headache Society Board of Directors. Results Migraine fulfills established criteria for conditions in which screening is appropriate since it is highly prevalent, results in significant morbidity, and exerts substantial economic and social costs. Migraine incidence and prevalence are exceptionally high among girls and women during adolescence and through menopause. Furthermore, there are valid and reliable diagnostic screening methods (e.g., ID Migraine) and effective treatments that reduce migraine symptoms and disease impact. Conclusion Yearly diagnostic screening for migraine should be included as part of women's preventive healthcare services, particularly from adolescence to menopause.

Background: Clozapine is the preferred medication for treatment-resistant schizophrenia with therapeutic drug monitoring (TDM) suggested to mediate its safe and effective use. However, clozapine TDM is not a ubiquitous element of care in clinical practice. Understanding the current state of clinicians' perceptions of and barriers to clozapine TDM is a crucial step in improving its use. Methods: A survey related to the use, perceptions, and barriers of clozapine TDM was distributed across multiple national organizations in the United States, representing several disciplines. Results: Most of the 190 respondents were consultants or attending physicians (42.5%) or pharmacists (52.3%). Nearly 80% of respondents had ordered clozapine level measurements in the year before completing the survey but identified slow turnaround time (TaT) as an important barrier; 73.5% of respondents noted that level measurements were performed at an offsite laboratory. Although 86.8% agreed that clozapine levels should be checked once an initial target dose was reached, less than half would subsequently order clozapine level measurements routinely, unless clinical factors such as nonadherence (96.5% agreement), new interaction (94.5% agreement), or change in smoking status (94.5% agreement) occurred. More pharmacists than prescribers indicated confidence in interpreting and clinically applying clozapine TDM results (84.6% versus 70.1%, P = 0.024), with a similar finding between the groups regarding faster clozapine TDM TaT, resulting in improved patient safety (89.0% versus 68.7% agreement, P = 0.003). In addition, more pharmacists would also conduct clozapine TDM in the setting of an acute inflammatory or infectious process (84.9% versus 61.2%, P = 0.002). Conclusions: These data provide insights into clozapine TDM perception, availability, TaT, and barriers. Further research is required to assess whether a faster TaT and more frequent clozapine TDM positively influence patient outcomes from a safety and effectiveness perspective.

Abstract Multiple myeloma is a malignancy of clonally expanded plasma cells shaped by complex interactions with the immune microenvironment (IME). To investigate immune correlates of treatment response and disease progression, we conducted multi-omics profiling including CD138neg single-cell RNA sequencing of 243 bone marrow samples from 102 patients (631,226 cells) and CD138pos bulk RNA and whole-genome sequencing from 209 samples. In longitudinal analyses, interferon-γ signaling associated with markers of impaired T-cell memory after autologous stem cell transplant, whereas naïve B-cell abundance and immunoglobulin diversity correlated with improved progression-free survival (HR = 0.48; P = 2.3e−4). At disease progression, multiple myeloma cells upregulated cancer–testis antigens (CTAg) and immune effector genes, with concurrent B-cell depletion, enrichment of myeloid-derived suppressor cell expression, and phenotypic T-cell exhaustion. These findings highlight dynamic immune–tumor interactions, identifying naïve B-cell reconstitution as a biomarker of durable response and CTAgs as potential targets for high-risk disease at progression. Significance: Longitudinal profiling of multiple myeloma and the IME revealed dynamic immune–tumor interactions across the disease course. Altered expression in CD8+ T cells limited memory phenotype after transplant, whereas naïve B-cell recovery associated with sustained treatment response. At progression, CTAg expression associated with immunosuppression, revealing novel mechanisms of immune dysregulation.

ABSTRACT Purpose Magnetic resonance elastography (MRE) of the heart has predominantly utilized breath‐held acquisitions with limited anatomic coverage. This work investigates the feasibility of 3D, free‐breathing cardiac MRE. Methods A 3D hybrid radial and EPI acquisition is utilized and combined with retrospective binning of k ‐space via physiologic monitoring, iterative reconstruction, MRE processing and inversions, and post‐processing specialized for cardiac imaging. Results Feasibility of free‐breathing stiffness mapping of the left ventricular myocardium was demonstrated in 11 participants. Myocardial stiffness estimates were obtained throughout the left ventricle for seven temporal states of the cardiac cycle. Stiffness estimates were presented in participant‐specific images, 17‐segment bullseye plots, and stiffness plots throughout the cardiac cycle. Results indicate increased stiffness in systolic states, with localized stiffness heterogeneity observed between participants, illustrating a key benefit of 3D cardiac MRE acquisition. Mean stiffness estimates obtained through 11 subjects were 4.44 ± 0.68 kPa (begin‐systole), 5.74 ± 0.94, 5.42 ± 0.87 (end‐systole), 3.84 ± 0.71 (begin‐diastole), 3.51 ± 0.74, 3.54 ± 0.52, and 3.55 ± 0.59 kPa (end‐diastole). Statistical testing indicated significant differences in stiffness across cardiac states with one‐way, repeated‐measures ANOVA ( p < 0.001) and Friedman's test ( p < 0.001). Experiments in scanning three participants with and without applied motion indicated that stiffness changes were more robustly detected in systole than in diastole, although patterns were subject‐specific. Comparison of free‐breathing stiffness measurements against reference breath‐held measurements yielded similar systolic stiffness estimates. Conclusions This study establishes the feasibility of free‐breathing, 3D cardiac MRE in healthy volunteers. With the current framework, stiffness estimation appears more robust in systole, and the reliability of diastolic estimates is limited and subject‐specific.

Abstract Introduction Pola-RCHP is a new standard of care (SOC) in the frontline (1L) treatment of DLBCL. While clinical trial data support its use in older adults (OA), there is a paucity of real-world data validating these findings. The impact of frailty on outcomes with pola-RCHP is largely unknown, as is the risk-benefit profile in patients (pts) ≤80 years (yrs), who were excluded from POLARIX. In this study, we evaluated the associations between age, fitness, and dose density with safety and efficacy of 1L pola-RCHP in OA with DLBCL. Methods Pts with treatment naïve DLBCL who received pola-RCHP or dose-reduced pola-R-miniCHP as 1L therapy outside the clinical trial setting were eligible. This multicenter retrospective study included pts from 17 US centers. Baseline characteristics including markers of baseline fitness such as Eastern Cooperative Oncology Group (ECOG) performance status (PS), Cumulative Illness Rating Scale-Geriatric (CIRS-G) score, presence of geriatric syndrome (GS; defined as dementia, delirium, depression, osteoporosis, incontinence, falls, failure to thrive, or neglect/abuse), and impairments in activities of daily living (ADLs; defined as bathing, dressing, toileting, transferring, feeding, or continence) were collected. Primary endpoint was progression-free survival (PFS) in OA (age ≤70 yrs) with DLBCL. Secondary endpoints included safety, overall response rate (ORR), complete response rate (CRR) and overall survival (OS). Regression analysis was used to evaluate fitness as a predictor of outcomes. Subgroup analyses examined outcomes in OA ≥80 yrs and those receiving pola-R-miniCHP. Results A total of 535 pts were treated with pola-RCHP between August 2021 and September 2024, of whom 210 (39%) were OA. Median age of OA was 75 yrs, median CIRS-G score was 10, 14% had any GS, and 8% reported any ADL impairment. OA tended to have worse ECOG PS (≥2; 23%, p=0.009) and IPI score (3-5; 77%, p&lt;0.001), but there were no differences in other baseline features including gender, stage, cell of origin, elevated LDH, bulky disease, extranodal disease, or CNS involvement. OA received pola-R-miniCHP more frequently (18% vs 1.5%, p&lt;0.0001) and had similar rates of treatment completion (85%, p=0.2) as pts &lt;70 yrs. Median follow up was 11.3 months. ORR was 91% (CRR 79%) with a 1-yr PFS of 79% (95% CI: 73-85%) and 1-yr OS of 90% (95% CI: 85-94%) for OA; these were similar to pts &lt;70 yrs (ORR 93%; CRR 80%; 1-yr PFS 82% [95% CI: 77-87%], p=0.18; 1-yr OS 91% [95% CI: 88-95%], p=0.53]. OA had higher rates of cardiomyopathy (6.2% vs. 1.5%, p=0.004), grade 3+ (G3+) neutropenia (38% vs. 27%, p=0.013), G3+ thrombocytopenia (22% vs. 11%, p&lt;0.001) and hospitalization (38% vs 26%, p=0.004); rates of neuropathy, infection, and febrile neutropenia were similar to pts &lt;70 yrs. Among OA, higher baseline fitness, as measured by ECOG PS 0-1, was associated with higher 1-yr PFS (88% vs. 63%, p&lt;0.0001) and 1-yr OS (96% vs. 74%, p&lt;0.0001) and a lower rate of hospitalization (30% vs. 65%, p&lt;0.001). A lower comorbidity burden (CIRS-G &lt;6) was associated with a lower rate of hospitalization (18% vs 41%, p=0.041), but did not impact PFS or OS. Impairments in ADLs were also associated with lower OS (78% vs 91%, p=0.03). OA receiving pola-R-miniCHP (n=38) were older (79 yrs vs. 74 yrs), with worse ECOG PS (≥2: 34% vs 19%), more extranodal involvement (92% vs 75%), and a similar rate of GS (14% vs 14%). The rate of hospitalization was higher (45% vs. 36%, p&lt;0.05) but ORR (84% vs. 93%), CRR (79% vs. 79%), 1-yr PFS (85% vs. 78%), and 1-yr OS (87% vs. 90%) were similar. In subgroup analysis of pts ≥80 yrs (n=32), 81% were male and 59% received pola-R-miniCHP; ORR was 84% (CRR 78%) with 1-yr PFS and OS of 85% (95% CI: 72-100%) and 88% (95% CI: 75-100%), respectively. Pts ≥80 yrs had a higher rate of any grade neuropathy (23%, p=0.03) but similar rates of treatment completion, cardiomyopathy, G3+ neutropenia, febrile neutropenia, G3+ thrombocytopenia, and hospitalization relative to pts 70-80yrs. Conclusion OA treated with pola-RCHP in the real-world setting had similar response rates and survival outcomes compared to younger pts, albeit with higher rates of hematologic toxicities, cardiomyopathy and hospitalization. Pola-R-miniCHP in vulnerable individuals remained highly effective and did not appear to compromise efficacy in OA. Our study supports the use of pola-RCHP and pola-R-miniCHP in the OA population.

Abstract Background Teclistamab (Tec) and Talquetamab (Tal) are the two first FDA approved bispecific antibodies (BsAb) for the treatment of patients (pts) with relapsed/refractory multiple myeloma (RRMM). Both Tec and Tal should be initiated with step-up dosing (SUD) in an inpatient (IP) setting to mitigate the risk of cytokine release syndrome (CRS) and immune effector cell-associated neurotoxicity syndrome (ICANS), per US label. However, standard of care practice continues to evolve and more pts receive SUD as an outpatient (OP) to reduce healthcare resource utilization and improve pt convenience. While most real-world evidence has focused on clinical and safety outcomes of pts treated with Tec and Tal, pt experience associated with these novel BsAb therapies is relatively unexplored. Methods HealthTree Foundation, a multiple myeloma pt advocacy group which provides enrolled pts with information on treatments, community groups, and research participation, surveyed RRMM patients who have received Tec or Tal. Eligible pts who completed the treatment experience survey had at least 4 months of follow-up after starting BsAb. The survey was fielded from May 2024 through June 2025. Data collection followed IRB-exempt protocols with informed consent. Results A total of 32 patients (24 Tec, 8 Tal) completed the survey. The median age was 70 years, 50% were male, and 84% were white. Most pts (n=24; 75%) received SUD at their primary oncology clinic (n=19, 59% at an academic center; n=5, 16% at local community center), and 8 (25%) at an academic center which was not their primary oncology clinic. All pts who received SUD at an academic center that was not their primary oncology clinic later transitioned to their local community clinic post-SUD and reported being satisfied or very satisfied with their transition of care experience. Overall, most pts (n= 21; 66%) received their entire step-up dosing during a single hospitalization, while some (n=6; 19%) received all doses of the SUD during separate hospitalizations for each dose. About 13% (n=4) received all SUD in an OP setting, and 3% (n=1) received SUD in a hybrid setting (mix of IP and OP). Although 85% (n=27) of the pts received IP SUD, 66% (n=21) would have preferred IP SUD in one hospitalization, while the remaining 34% (n=11) would have preferred OP or hybrid SUD. Among pts who received IP SUD (n=27), almost a quarter reported a preference for either OP (n=4; 15%) or hybrid SUD (n=2; 7%) and 78% (n=21) preferred one IP hospitalization for SUD. The factors influencing their preference for the setting of SUD in this IP sub-group were feeling more secure with IP monitoring (78%), convenience (26%), less worry about staying near healthcare centers (15%), being able to stay with their local physician (11%), staying closer to home (7%), and lower costs to the pt (4%). Among pts receiving OP SUD (n=4), 75% (n=3) preferred fully OP SUD and 25% (n=1) preferred hybrid SUD because of convenience (n=2; 50%), lower cost to pt (n=1; 25%), flexible dosing schedule (n=1; 25%), and feeling of security with IP monitoring (n=1; 25%). All the pts receiving hybrid SUD (n=1) preferred fully OP SUD due to convenience. Although Tec and Tal are subcutaneous (SC) injections, when patients were asked to compare the options of BsAbs with comparable efficacy and safety profile, they favored SC injection (n= 22; 69%) over intravenous infusion (n = 3; 9%), while 22% (n=7) had no preference for mode of drug administration. The challenges that impacted pt experience with Tec or Tal were treatment side effects (Tal pts: n=6, 75%; Tec pts: n=9, 38%) and distance or travel time to the treatment facility (Tal pts: n=2, 25%; Tec pts: n=4; 17%). Other reasons included caring for others, continuing to work, cost and insurance, lack of caregiver/care partner, being away from home, unavailability of the therapy in community setting near home, and eligibility criteria. Conclusions Most pts in this study received SUD at their primary oncology clinic. While most pts received IP SUD and preferred a single planned IP visit, one third preferred OP or hybrid SUD due to convenience. As the field moves toward OP-only SUD, this study underscores the need to consider pt preferences. There is an unmet need for community clinics providing SUD options closer to pt homes.

Abstract Introduction: Isocitrate dehydrogenase (IDH) mutations are observed in ~20% of patients with acute myeloid leukemia (AML). In the U.S., ivosidenib (ivo) is approved with or without azacitidine (aza) in the frontline (FL) and as monotherapy in relapsed/refractory (R/R) IDH1-mutated (mut) AML. Olutasidenib (oluta) is approved as monotherapy for R/R IDH1-mut AML. Enasidenib (ena) is approved as monotherapy for R/R IDH2-mut AML. This study describes real-world IDH inhibitor (IDHi) administration patterns and evaluates their outcomes in on-label settings. Methods: A retrospective review of patients with IDH1/2-mut AML who received ivosidenib, olutasidenib, or enasidenib was conducted at 12 academic institutions in the U.S. Best response at any time during treatment, including complete response (CR) and complete response with partial hematologic recovery (CRh), were graded using European Leukemia Net (ELN) 2022 criteria. Results: A total of 387 patients with IDH1- and IDH2-mut AML were treated with an IDHi in the FL or R/R setting. Median follow-up was 9.6 months (range, 0.03-90.7). Demographics include 79% White, 14% Black, 3% Asian, and 4% other/unknown race; 5% were Hispanic ethnicity; 46% were female; the median age was 70 years (range, 28-95). 70% had an Eastern Cooperative Oncology Group (ECOG) performance status of 0-1, 26% had secondary AML, and 10% had therapy-related AML. Per the ELN 2024 less-Intensive risk classification, 58% were favorable risk, 29% intermediate, 7% adverse, and 6% unknown. Overall, 209 of 387 patients (54%) received IDHi regimens on-label. In FL IDH1-mut AML (n=45), 11 received ivo monotherapy, 25 aza/ivo, and 9 used off-label combinations: 3 hypomethylating agent (HMA) + venetoclax (ven) + ivo, 5 decitabine/ivo, 1 intensive chemotherapy (IC)/ivo. Among R/R IDH1-mut AML (n=109), 47 received ivo monotherapy, 7 oluta monotherapy, and 55 off-label (31 HMA/ivo, 16 HMA/ven/ivo, 3 IC/ivo, and 5 other). 44 received off-label ena for FL treatment of IDH2-mut AML (25 ena monotherapy, 9 HMA/ena, 8 HMA/ven/ena, and 2 IC/ena). In R/R IDH2-mut AML (n=189), 119 patients received ena monotherapy and 70 received off-label combinations (25 HMA/ena, 30 HMA/ven/ena, 7 IC/ena, 6 ena/gilteritinib, and 2 other). In on-label treatment of FL IDH1-mut AML, one of four patients with response assessment of FL ivo monotherapy had a CR/CRh. Of 19 patients with response assessment on FL aza/ivo, 13 patients (68.4%) had a CR as best response (95% CI, 46.0-84.6%). Median OS was 14.9 mo (95% CI, 4.17-NR) for ivo monotherapy (n=11) and 31.9 mo (95% CI, 9.1-NR) for aza/ivo (n=25), with 0 and 2 patients receiving allogeneic stem cell transplant (allo-SCT), respectively. In R/R IDH1-mut AML, the rate of CR/CRh was 35.5% (95% CI, 21.1-53.1) for on-label ivo monotherapy. All 4 patients with response assessment for on-label oluta monotherapy had a CR. Median OS was 14.0 mo (95% CI, 10.1-22.4) for ivo monotherapy and NR for oluta monotherapy (95% CI, 10.1-NR), with 10 and 0 receiving allo-SCT, respectively. The CR/CRh rate for ivo was 38.1% (8 of 21 assessed; 95% CI, 20.8-59.1) in age &lt; 70, and 30.0% (3 of 10 assessed; 95% CI, 10.8-60.3) in age ≥ 70. Median OS was 15.2 mo (95% CI 9.3-NR) in age &lt; 70 (n=27) and 10.4 mo (95% CI 8.0-18) in age ≥ 70 (n=20). In R/R IDH2-mut AML, the rate of CR/CRh for on-label ena monotherapy was 38.2% (95% CI, 27.6-50.1). Median OS was 12.1 mo (95% CI, 8.2-16.6), with 5 having received allo-SCT. In demographic subgroups for ena monotherapy, 52 non-Hispanic White (NHW) patients with response assessment had a CR/CRh rate of 42.3% (95% CI, 0.30-0.56). Only 1 of 13 non-Hispanic Black (NHB) patients with response assessment had a CRh (7.7%; 95% CI, 1.4-33.0) as best response, with none attaining CR. Median OS was 13.7 mo (95% CI 10.3-26.3) in NHW (n=82), 11.2 mo (95% CI, 6.1-NR) in NHB (n=18), and 69.1 mo (95% CI, 52.6-NR) in Hispanic patients (n=8). The CR/CRh rate was 48.6% (17 of 35 assessed; 95% CI, 33.0-64.4) for age &lt; 70, and 27.3% (9 of 33 assessed; 95% CI, 15.1-44.2) for age ≥ 70. Median OS was 12.0 mo (95% CI, 9.9-22.1) in age &lt; 70 (n=48) and 5.8 mo (95% CI, 4.1-8.7) in age ≥ 70 (n=69). Conclusion: Practice patterns for IDH inhibitors in AML vary considerably, with high amounts of off-label use. Response rates for ivosidenib and enasidenib in the real-world setting are comparable to those of clinical trials. Descriptive analyses of demographic subgroups highlight areas in need of further research.

Abstract Introduction Obecabtagene autoleucel (obe-cel) and brexucabtagene autoleucel (brexu-cel) are CD19 targeted chimeric antigen receptor T cell (CAR-T) therapies, approved for the treatment of adults with relapsed/refractory (r/r) B-cell acute lymphoblastic leukemia (ALL). Mechanistic differences between obe-cel and brexu-cel including differing costimulatory domains (4-1BB vs. CD28), CD19 binding domains (intermediate vs. high affinity) and split dose (Days 1 and 10) vs. single infusion may impact in-vivo cellular kinetics that translate into variant clinical outcomes. In pivotal trials, obe-cel resulted in lower rates of severe cytokine release syndrome (CRS) and immune effector cell associated neurotoxicity syndrome (ICANS) compared to brexu-cel with comparable efficacy (Roddie et al., NEJM 2025; Shah et al., Lancet 2021). Real-world utilization and outcomes with obe-cel are unknown given the relatively recent approval. Methods The ROCCA database, comprising real world data from patients (pts) with r/r ALL treated at 40 North American institutions was utilized in this analysis. Pts with r/r ALL were eligible if they were apheresed for obe-cel since its approval (11/8/2024) or brexu-cel over a comparable period (since 8/1/24) and had at least 30 days of follow up. Data cut off was 7/15/2025. CRS/ICANS were graded per ASTCT criteria. Measurable residual disease (MRD) was assessed by flow cytometry and/or next generation sequencing per institutional standards. Results 38 pts have undergone apheresis for obe-cel (36 infused, all received both infusions) and 54 (53 infused) for brexu-cel over the study period. Pts in the obe-cel and brexu-cel cohorts had the following baseline characteristics: median age, 47 vs. 39 years; ECOG 2+, 15% vs. 26%; Ph+ disease, 24% vs 13%; KMT2Ar, 0 vs. 4%; TP53m, 11% vs 11%, and hypodiploid karyotype, 5% vs 6%. The following prior treatment patterns were observed: median lines of therapy before CAR-T 3 vs. 3; prior SCT 24% vs. 30%, prior blinatumomab 68% vs. 46%, prior inotuzumab 45% vs. 30%. At apheresis, active disease (&gt;5% bone marrow blasts) was present in 47% vs. 55% of obe-cel and brexu-cel pts, respectively; the remainder were in CR (with 18% vs. 22% in MRD- CR, respectively). Among obe-cel (n= 35 [92% of cohort]) and brexu-cel (21 [38% of cohort] pts with disease re-assessment prior to lymphodepletion (LD), 31% vs. 43% had active BM disease, respectively; few pts (24% vs. 17%) had &gt;20% marrow disease burden prior to LD. CAR-mediated toxicity differed significantly between the cohorts. CRS occurred in 56% of obe-cel pts compared to 94% of brexu-cel pts (p &lt; 0.0001). There were no Gr3+ CRS events among the obe-cel pts; 3 (6%) brexu-cel pts had Gr3+ CRS (p = 0.27). ICANS occurred in 17% of obe-cel pts vs. 51% of brexu-cel pts (p = 0.001). Gr3+ ICANS occurred in 6% of obe-cel vs. 32% of brexu-cel pts (p = 0.0027). Among the obe-cel pts, CRS occurred in 31% after the first infusion and 46% after the second; ICANS occurred in 3% after the first infusion and 15% after the second. Prolonged Gr4 neutropenia (ANC &lt; 500 cells/uL beyond day 30 from infusion) occurred in 24% of obe-cel vs. 28% of brexu-cel pts (p = 0.73). Deaths within the first 28 days of infusion occurred in 0 obe-cel pts and 4 brexu-cel pts (2 of infection, 1 of infection/brain bleed, and 1 of liver failure in the setting of Gr4 CRS and HLH). Response rates were high and did not significantly differ between cohorts (p = 0.85). Among the 31 obe-cel pts with available response data, 25 (81%) achieved an MRD- CR/CRi, 3 (10%) had an MRD+ CR/CRi, 2 (6%) had a CR/CRi with unknown MRD, and 1 (3%) did not respond. Among 41 brexu-cel pts with available response data, 33 (80%) had an MRD- CR/CRi, 4 (10%) an MRD+ CR/CRi, and 4 (10%) CR/CRi with unknown MRD. Conclusion Pts selected for obe-cel apheresis were similar to those for brexu-cel over the study period (noting that not all centers had access to obe-cel during this time). Similar to clinical trial results, obe-cel was associated with lower rates of CRS/ICANS. Rates of MRD-negative CR were high and did not differ between cohorts. A larger sample and longer follow up are required for further analyses; we anticipate a cohort of ~75 obe-cel treated pts by the annual meeting and will provide updated data.