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Abstract Introduction 0.05% Chlorhexidine Gluconate (CHG) has gained popularity as an irrigant for inflatable penile prosthesis (IPP). In vitro data has explored interactions between CHG and minocycline/rifampin impregnated (M/R) IPP surfaces Objective We aimed to assess clinical infection rates between intraoperative CHG use and M/R impregnated IPPs in a large multi-institutional cohort. Methods We conducted a retrospective analysis of 1,604 patients who underwent IPP implantation across 12 referral centers. Data collection spanned from January 1, 2017 to March 1, 2024. Each surgeon contributed patients who underwent IPP implantation with the use of CHG as an irrigant and an equal number of consecutive control patients where CHG was not used. The primary outcome was explant for postoperative infection. Patient demographics were compared using chi squared testing and logistic regression analysis was performed to assess factors associated with infection. Results M/R impregnated devices accounted for 695 cases. The incidence of infection with intraoperative CHG use was 1.7% (5/289) and was not significantly different from the 2.5% (10/406) infection rate in those without CHG (p=0.429). Patients with infection had a higher prevalence of hypertension and history of priapism (Table 1). On logistic regression analysis, only a history of priapism was significantly associated with an increased odds of infection (OR 11.47, 95%CI 2.25-58.40, p=0.003). Intraoperative CHG use was not associated with postoperative infection (OR 0.69, 95%CI 0.2-2.06. p=0.514). Conclusions In a large multi-institutional cohort, there was no difference in infection rate for patients with or without intraoperative CHG use, consistent with prior in vitro findings. Disclosure Any of the authors act as a consultant, employee or shareholder of an industry for: Intuitive Surgical, Fidelis, Urofill, Boston Scientific, Coloplast, Cynosure, Antares Pharma, Clarus Pharmaceuticals, Acerus Pharma; Endo Pharma.

Abstract Introduction 0.05% Chlorhexidine Gluconate (CHG) has increasingly been used as an irrigant for inflatable penile prosthesis (IPP) surgery. Recent in vitro data shows mixed results regarding efficacy, but clinical data is lacking. Objective To explore the cultured organisms and infection characteristics of IPP infections with and without intraoperative CHG use from a large multi-institutional cohort. Methods We queried a retrospective multi-institutional database of patients who underwent IPP placement for cases resulting in IPP Infection. We stratified cases by intraoperative use of CHG as an irrigant or dip. We compared patient and infection characteristics using chi squared tests and independent t-tests. Culture data from IPP explant was reviewed for descriptive analysis. Results We identified 70 IPP infections, 43 with intraoperative CHG use. Patient demographics were similar between infection cohorts. (Table 1). Median time to infection was similar, 46.5 days in the CHG cohort and 34 days in the non-CHG cohort (p=0.518). Culture data were available for 57 (81.4%) patients. For CHG IPP infections, 8 had Escherichia coli cultured at time of explant and 6 grew methicillin sensitive Staphylococcus aureus. For non-CHG IPP infections, Staphylococcus epidermidis (4) and Pseudomonas aeruginosa (3) were the most common cultured organisms. A total of nine unique organisms were cultured for both CHG and non-CHG infections. Negative growth cultures were recorded for 2 patients in both the CHG and non-CHG infection groups. (Figure 1) Conclusions In a large, multi-institutional cohort, IPP infections after intraoperative CHG use were associated with a variety of cultured organisms, most commonly Escherichia coli and Methicillin sensitive Staphylococcus aureus. Disclosure Any of the authors act as a consultant, employee or shareholder of an industry for: Coloplast: Advisory board, speaker; Endo: Advisory board; Haleon: Advisory board; Halozyme: Advisory board, speaker; Masimo: Intellectual property; Softwave: Advisory board; Sprout: Consultant; Vertica: Research investigator; Xialla: Advisory board.

Abstract BACKGROUND Children exposed to poverty during frontline therapy for B-lymphoblastic leukemia (B-ALL) experience inferior overall survival (OS), higher relapse rates, and earlier relapse than their peers. Real-world data describing treatment patterns and survival after relapse of B-ALL are lacking and, as a result, the impact of poverty following relapse remains poorly understood. This study evaluated the association of poverty exposure, proxied by insurance status, with post-relapse survival and explored potential explanatory mechanisms, including disease biology and therapy utilization. METHODS Data from Retrospective Study of Contemporary Approaches to First Relapse in B-ALL (ReCALL-1), a multicenter retrospective cohort study of patients < 30 years old with first relapse of B-ALL from 2018-2022, were used. The primary exposure was poverty, proxied by insurance status at relapse, categorized as any private insurance (poverty unexposed), public-only insurance (poverty exposed), no insurance, or unknown; the latter two were not included in comparative analyses due to low numbers. The primary outcome was OS. Secondary outcomes included measurable residual disease (MRD)-negative second complete remission (CR2), relapse after CR2, non-relapse mortality (NRM), with relapse treated as a competing risk, and receipt of cellular and immunotherapies. RESULTS Among 462 patients from 31 U.S. institutions, 41% had private insurance, 47% public-only insurance, 2% no insurance, and 10% unknown. Compared to privately insured patients, those with public insurance were more likely to be Hispanic (56% vs 19%, p<0.001) and have non-English preferred language (30% vs 6%, p<0.001). Non-Hispanic Black patients comprised 9% of those with public insurance and 5% of those with private insurance. Disease characteristics that differed by insurance status at relapse included: Ph-like cytogenetics, more common in publicly insured (23% vs 11%, p=0.002), and infant ALL, more common in privately insured patients (10% vs 5%, p=0.06). Publicly insured patients were more likely to have experienced major organ toxicity during frontline therapy (32% vs 18%, p=0.002) and very early relapse (<18m from diagnosis: 43% vs 32%, p=0.07). Other demographic and disease characteristics, including relapse site and cytomolecular features, were similar by insurance status. With a median follow-up of 51 months from relapse, 4-year OS differed by insurance (log-rank p=0.02): 72% for private vs 56% for public insurance. After adjusting for race/ethnicity and language, public insurance increased the hazard of death by 65% (aHR 1.65 95% CI 1.13-2.42, p=0.004). The association remained, but was attenuated, when unbalanced disease characteristics (time to relapse, infant ALL, Ph-like cytogenetics, prior organ dysfunction) were included (aHR 1.47, 95% CI 1.00-2.16, p=0.05). Rates of MRD-negative CR2 were similar (85% public vs 87% private). However, point estimates suggested publicly insured patients had more relapse after CR2 (44% vs 37%, p=0.42) and higher 4-year NRM (16% vs 10%, Gray's test p=0.12), though neither were significant. Treatment choices for first relapse did not differ by insurance status. Utilization of intensive reinduction (91% vs 95% for public vs private, p=0.18) and clinical trial enrollment (22% for both) were similar. Receipt of cellular therapies did not significantly differ by public vs private insurance: Chimeric Antigen Receptor-T cells (CAR-T: 38% vs 34%, p=0.41), hematopoietic cell transplant (HCT: 42% vs 47%, p=0.32). Use of blinatumomab trended higher in those with private insurance (36% vs 45%, p=0.07), and inotuzumab was similar (11% for both, p=0.87). Median time from relapse to CAR-T or HCT was comparable (to CAR-T 102 vs 100 days, to HCT 117 vs 114 days). CONCLUSION This is the first study to demonstrate differential survival by insurance type, a proxy for poverty exposure, after first relapse of B-ALL. In this large multicenter, real-world cohort, patients with public insurance had worse OS after relapse than those with private insurance. The survival disparity existed independent of other SDOH factors. Adjustment for known high-risk disease features only partially accounted for the observed differences in OS. In contrast, rates of MRD-negative CR2 and receipt of CAR-T and HCT were comparable across insurance types. These findings highlight the urgent need to identify effective interventions that will ensure equitable outcomes after relapse.

Abstract Background: Undetectable minimal residual disease (uMRD) at the end of first-line (1L) treatment (tx) with 12-cycles (C) of venetoclax (ven) + obinutuzumab (obin) is associated with prolonged survival for patients (pts) with chronic lymphocytic leukemia (CLL, Al Sawaf et al. Blood 2024). We hypothesized that MRD may be used to guide ven tx duration for CLL pts treated with 1L ven + obin. Methods In this ongoing phase II, multicenter investigator-initiated study, pts receive ven + obin for 1L tx of CLL/small lymphocytic lymphoma (NCT04447768). Eligible pts have a CIRS score of ≤ 6 and require 1L tx per iwCLL 2018 criteria. Pts receive 6 x 28-day C of obin and initiate ven on C1D22. Ven duration is dependent on peripheral blood (PB) MRD status measured by ClonoSeq next generation sequencing. At C7, pts undergo MRD testing. Pts uMRD6 (<10-6 sensitivity) at both C7 and C9 dc ven after 9C and enter treatment free observation (TFO). Pts with detectable MRD6 (dMRD6) at C7 undergo repeat testing at C12; if uMRD5 (<10-5) pts dc ven after 12C. Pts dMRD5 at C12 continue ven for an additional 12C (24C total) prior to TFO. The primary study endpoint is 36-month PFS; the unpromising rate is set at 82% and will be tested by a nonparametric survival estimate (Kaplan-Meier) along with Greenwood's formula. RNA sequencing (RNAseq) was performed pre-tx on patient bone marrow (or PB if inaspirable) samples. Unsupervised clustering using machine learning (ML) based on consensus nonnegative matrix factorization was applied to the most variable genes to identify patient clusters. Clusters were then biologically characterized by gene signature scoring using xCell algorithm and assessed for association with uMRD6 at C7 using a Fisher exact test. Results Baseline characteristics of the 100 pts who initiated tx include: median age 58 (range 34-81); 71% male, 90% White, 3% Black and 2% Asian, 5% unknown; 49% IGHV unmutated, 16% TP53 mutation, 8% del17p (previously reported, Roeker et al. ASH 2024). 3 pts stopped tx prior to C7. 51 pts were uMRD6 at C7 and C9 and completed 9C ven. 46 pts were dMRD6 at C7; 6 pts stopped tx outside of meeting protocol requirements and are included in intention-to-treat (IIT) analyses. 32 pts were uMRD5 at C12 and dc ven after 12C. 8 pts were dMRD5 at C12: 5 continued ven per protocol (3 completed 24C ven, 2 ongoing tx as of 15 May 2025 data cut-off), 2 stopped ven outside of protocol requirements (included in ITT analyses), and 1 pt withdrew consent. At a median follow-up of 35 months, the 36-month PFS rate is 90% (95% CI: 84%, 97%). 36-month OS is 94% (95% CI: 89%, 99%). Landmark PFS analyses from EOT were performed for pts who dc ven after 9C due to uMRD6 (24-month PFS 92%, 95% CI: 85, 100%, n=51) and pts who dc ven after 12C due to uMRD5 (24-month PFS 96%, 95% CI: 89%, 100%, n=32). For pts dc ven after 9C due to uMRD6 (n=51), PB MRD at 12C after EOT was: 59% uMRD6, 12% uMRD5, 4% uMRD4, 8% dMRD4 and 18% unknown. For pts dc ven after 12C due to uMRD5 status (n=32), PB MRD at 12C following EOT was: 9% uMRD6, 31% uMRD5, 9% uMRD4, 25% dMRD4 and 25% unknown. Of the 5 pts with PD, 3 pts have had Richter Transformation to diffuse large B-cell lymphoma (all uMRD6 at C7 / 9). Two pts with PD have not met iwCLL tx criteria and remain in TFO. Five pts have died (suicide, West Nile encephalitis, COVID-19, complications of glioblastoma and RT DLBCL). Five C12 dMRD5 pts who continued ven have reached C18, with only 1 of 5 converting to uMRD5 in PB. However, all 5 maintained uMRD4 (<10-4). Of 3 pts that completed 24C ven (2 ongoing tx), 1 pt had deepening of response to uMRD5 at C24, and 2 pts had rising MRD on ven (dMRD4 at C24). To investigate patient heterogeneity at baseline and its relationship to uMRD, we clustered patient RNAseq samples into two clusters using artificial intelligence/ML based unsupervised clustering. The clusters associated with uMRD6 at C7 (Fisher exact test p=0.038), and patients in the cluster with significantly higher immunosuppressive cells such as T-regulatory cells and M2 macrophages were less likely to be uMRD6 at C7. Conclusions At a median follow-up of 35 months, the estimated 36-month PFS rate is 90%. RNAseq transcriptomic analyses identified that patients with enriched immunosuppressive cells were less likely to be uMRD6 at C7. Additional follow-up is required to confirm the durability of this MRD-guided ven + obin tx strategy.

Abstract Introduction: Waldenström macroglobulinemia (WM) is characterized by the presence of a MYD88 mutation in >90% and a CXCR4 mutation in 30-40% of cases. The impact of these mutations on treatment responses and disease outcomes is well known. TP53 alterations (TP53ALT) have more recently been described in WM and are reported to occur in up to 25% of patients, with a higher frequency in patients with previously treated WM, especially those with prior alkylator or nucleoside analogue exposure (Tam et al Blood Adv 2024; Poulain et al CCR 2017; Tsakmaklis et al, ASH 2025). TP53 ALT WM is associated with a shorter time to disease progression, as well as worse overall survival (Poulain et al CCR 2017; Gustine et al, BJH 2019). Depth of response to BTK inhibitors is affected by TP53 status, with recent data reporting a very good partial response (VGPR) rate of 34% v. 25% and major response rates of 84% v. 73% in patients without or with a TP53 ALT (Tam et al Blood Adv 2024). No complete responses were reported and median PFS was shorter in those with a TP53ALT compared with wild-type (TP53WT). Loncastuximab tesirine is a humanized IgG1 anti-CD19 antibody that is conjugated to a pyrrolobenzodiazepine (PBD) dimer. Following internalization, the PBD dimer is released via proteolytic cleavage and binds to the DNA minor groove forming highly cytotoxic DNA inter-strand crosslinks. Cells deficient in DNA repair including TP53 alterations are vulnerable to the cytotoxic effects of loncastuximab tesirine (Tarantelli et al, Haematologica 2024). Methods: In an ongoing investigator-initiated, prospective phase II study in symptomatic patients with relapsed or refractory WM (NCT05190705), patients are receiving single agent loncastuximab tesirine. Loncastuximab tesirine is administered at 150 ug/kg in cycles 1 and 2 and 75 ug/kg in cycles 3 to 6. Each cycle is 28 days. The primary outcome measure of this study is attainment of VGPR or complete (VGPR/CR) response. The accrual goal of this trial is 20 patients, based on an alternative VGPR/CR rate ≥40% versus a null of ≤10%, with a double-sided alpha of 0.037 and a power of 87%. The study would meet its endpoint if ≥6 patients attained a VGPR/CR. Results: Of the 14 patients who have completed therapy on this trial to date, the median age is 71 years (range 53-81), 9 (64%) are male, and the median prior number of therapies is 4 (range 2-10). Median baseline hemoglobin is 9.5 g/dL (range 8.2-12.6), serum IgM is 2146 mg/dL (range 723-5955), and bone marrow involvement is 53% (range <5-90). Four patients had extramedullary disease. Twelve patients (86%) are MYD88 mutated; 8 patients (57%) are CXCR4 mutated, and 8 (57%) are TP53 altered. Nine patients completed all 6 cycles of therapy. Of the 5 other patients, treatment was stopped early due to GGT elevation (n=2), disease progression (n=1), patient decision (n=1), and skin toxicity (n=1). No IgM flare and no infusion reactions have occurred. For all patients, the median time to minor response, major response, and deepest response was 28, 55, and 172 days, respectively. The response rates include 1 (7%) CR; 9 (64%) VGPRs; 2 (14%) partial responses (PR); 1 (7%) minor response; and 1 (7%) progressive disease, for an overall response rate of 93% and a VGPR/CR rate of 71%. For the 8 patients with TP53ALT, the baseline characteristics were as follows: 50% male; median age of 70 years (range 53-77), median prior therapies is 4 (range 2-10); median IgM is 1877 mg/dL (range 723-5639); and median hemoglobin is 9.2 g/dL (range 8.2-11.6). All TP53ALT patients had an MYD88 mutation, and 6 (75%) carried a CXCR4 mutation. For those with TP53 ALT, the median time to minor response, major response, and deepest response was 28, 49, and 235 days, respectively. All TP53ALT patients attained a major response; 1 patient (13%) with a CR, 6 (75%) with a VGPR, and 1 (13%) with a PR, for an overall response rate of 100% and a VGPR/CR rate of 89%. One patient had splenomegaly and one had adenopathy, both of which resolved after treatment. Conclusion: Our findings from this ongoing, prospective trial demonstrate a high VGPR/CR rate of 71% in heavily pre-treated WM. Notable, is the VGPR/CR rate of 89% in high-risk patients with TP53ALT WM. No unexpected toxicities have been seen in this trial. Our findings identify a potentially novel time-limited therapy in relapsed or refractory WM, including patients with high-risk TP53ALT WM.

Abstract Introduction Pronounced disparities in pediatric B-lymphoblastic leukemia (B-ALL) outcomes by race and ethnicity persist in the contemporary era. Gaps in overall survival (OS) from initial diagnosis are wider than event-free survival, suggesting that post-relapse mechanisms may contribute. However, data on treatment and outcomes after relapse are lacking. In a large, multicenter, real-world cohort of children and young adults with high-risk 1st relapse of B-ALL, we sought to (1) define survival outcomes by race/ethnicity and (2) explore if differences in therapy utilization drive outcomes. Methods We conducted an analysis within the Retrospective Study of Contemporary Approaches to 1st Relapse in B-ALL (ReCALL-1) cohort, which includes patients <30 years who initiated 1st relapse therapy between 2018-2022. This analysis was restricted to patients treated at US centers for “high-risk” 1st relapse, defined as relapse for which hematopoietic cell transplant (HCT) is generally standard-of-care: Early relapse (medullary <36m; isolated extramedullary <18m), late relapse with persistent end of reinduction disease, Ph+ B-ALL or age ≥18 years. Patients with Trisomy 21, those who received cell therapy before relapse and those who died during reinduction were excluded. The primary exposure was race/ethnicity categorized as Hispanic, non-Hispanic Black (NHB), non-Hispanic White (NHW), and other/unknown. The primary outcome was OS from relapse. Multivariable Cox regression models were constructed to include other social drivers of health (SDOH; health insurance, preferred language) and disease characteristics. Results Of 479 patients in ReCALL-1, 311 from 31 centers met inclusion for this analysis (41% Hispanic, 7% NHB, 46% NHW, 5% NH-other/unknown). With a median follow-up of 47m, OS differed by race/ethnicity (log-rank p=0.017): Hispanic, 4y OS 59%; NHB, 37%; NHW, 68%. Compared to NHW patients, NHB patients had an increased hazard of death (HR 2.3, 95% CI 1.3-4.3, p=0.006), while Hispanic patients were more similar to NHW patients (HR 1.3, 95% CI 0.9-2.0, p=0.16). Adjustment for SDOH only marginally attenuated the risk for NHB patients (aHR 2.0, 95% CI, 1.1-3.7, p=0.031) and led to equivalent outcomes for Hispanic patients (aHR 0.9, 95% CI, 0.5-1.5, p=0.66). Adjusting for disease characteristics that differed by race/ethnicity at p<0.2 (time to relapse, Ph+, Ph-like, KMT2Ar, age ≥18, or relapsed infant ALL) did not diminish the risk for NHB patients (aHR 2.0, 95% CI, 1.1-3.7, p=0.032) while outcomes remained equivalent for Hispanic patients (aHR 1.2, 95% CI, 0.8-1.8, p=0.40). Point estimates of cumulative incidence of non-relapse mortality (NRM) were highest in NHB patients (Hispanic, 4y NRM 13%, NHB 22%, NHW 11%), but this trend was not statistically significant (Gray’s p=0.52). Only 17% of patients initiated therapy for relapse on a clinical trial with no differences observed by race/ethnicity. Most patients received definitive treatment for relapse with either CAR T cell therapy (CART) or HCT: 79% overall, 74% Hispanic, 91% NHB, and 83% NHW. CART and HCT were utilized equally (39% and 40%, respectively) and the proportion that received each therapy did not vary by race/ethnicity. Time to CART/HCT, external referral for treatment, receipt of investigational v commercial CART, and use of post-CART consolidative HCT revealed no differences by race/ethnicity. Of the 66 patients (21%) who did not receive cell therapy, 26 had planned for CART or HCT, but did not receive due to disease progression or NRM (n=24; 12 Hispanic, 10 NHW), or insurance barriers (n=2, both Hispanic). After HCT, OS was worse for NHB patients (log-rank p=0.03) with 4y OS of 42% v 85% for NHW and 75% for Hispanic. Post-CART, 4y OS was 40% for NHB v 59% for NHW and 51% for Hispanic, but this difference was not statistically significant. Conclusion In a large real-world cohort of children with high-risk 1st relapse of B-ALL, we found a two-fold increased hazard of death for NHB patients compared to NHW patients, even after adjustment for other SDOH factors and high-risk disease features. In contrast to previous studies of adult patients, children appeared to have equal access to cell therapies across races/ethnicities. We found that Hispanic patients, who comprised >40% of the cohort, had similar survival to NHW children, suggesting that availability of cellular and immunotherapies may be mitigating historically observed disparities for children with relapsed B-ALL.

Abstract INTRODUCTION Outcomes for 1st relapse of pediatric B-lymphoblastic leukemia (B-ALL), especially high/intermediate-risk (HR/IR) relapse, remain unacceptably poor. Limited enrollment of this population on cooperative group clinical trials has impeded our ability to study potentially effective regimens. In the current era, patients can access innovative immunotherapies commercially. However, there is no mechanism to capture outcomes for these off-study patients and no comparative effectiveness data to guide treatment selection. METHODS We conducted a multicenter, retrospective study of patients <30 years who initiated 1st relapse therapy at a participating center from 2018-2022 (ReCALL-1 Study). Objectives were to define real-world survival outcomes, compare response rates of reinduction strategies, describe the post-reinduction treatment landscape, and, for patients with HR/IR relapse, assess the comparative effectiveness (CE) of blinatumomab to hematopoietic cell transplant (blina/HCT) v CD19 CAR T cells (CART). For the CE analysis, we emulated an open-label, randomized study of blina/HCT v CART who achieved an M1/M2 marrow at the end of an intensive reinduction (EoRI). Patients were classified by their intended treatment at EoRI. Cox regression models were used to adjust for unbalanced patient and disease features by arms. The primary outcome was overall survival (OS) from EoRI. RESULTS The full cohort included 479 patients from 33 centers (31 US, 2 international). Median time to relapse was 31 months (m); 77% had bone marrow (BM) involvement and 31% central nervous sytem involvement. With a median follow-up of 49m from relapse, 4 year (y) OS, event-free survival (EFS), and non-relapse mortality (NRM) were 64%, 43%, and 13%, respectively. Among patients with very early BM (<18m, n=79), early BM (18-35m, n=76), late BM (≥36m, n=162), and isolated CNS (n=85) relapses, 4y OS/EFS were 29%/20%, 57%/35%, 78%/49%, and 84%/61%, respectively. Only 19% received reinduction therapy on a clinical trial. Among patients with BM disease, R3 reinduction (n=179) and VXLD (n=61) had identical MRD-negative (<0.01%) CR rates of 38% (p=1.00) and equivalent treatment failure (TF; M3 or extramedullary disease) rates: R3, 8% v VXLD 7%, p=0.79. Blina (n=33) and inotuzumab-based (n=21) reinductions achieved MRD-negative CR rates of 39% and 52%, respectively, but higher TF rates of 39% and 24%. Reinduction mortality was 2%: R3, n=5; VXLD, n=3; 3-drug reinduction, n=1. Overall, as part of 1st relapse therapy, 36% received CART (78% commercial product), 44% HCT, 40% blina, and 11% inotuzumab. The emulated trial included 159 patients, 95 on blina/HCT and 64 on CART. Study arms were well matched by demographics, cytogenetics, and relapse sites, but CART patients were more likely to have relapsed <18m from diagnosis (34% v 24%) and have EoRI M2 marrows (31% v 11%), and less likely to have private insurance (36% v 51%). Unadjusted OS was comparable between arms (log rank p=0.18): CART, 60% at 4y; blina/HCT, 71%, as was NRM (10% v 13% at 4y). EFS was lower for CART (p=0.049): 4y EFS 35% v 49% for blina/HCT. After adjustment for unbalanced covariates, the hazard of death was equivalent for CART as compared to blina/HCT (aHR 1.1, 95% CI 0.6-2.1, p=0.67) and EFS became more comparable (aHR 1.3, 95% CI 0.8-2.1, p=0.22). 91% of blina/HCT and 97% of CART received their intended cell therapy; time from EoRI to cell therapy was shorter for CART (67 v 86 days, p<.001). In the CART arm, 34% underwent consolidative HCT; 1/3 were preplanned and 2/3 due to loss of B cell aplasia or NGS-MRD positivity. Of those with a 2nd relapse, CART patients were more likely to be CD19 negative (47% v 10%, p=0.003). CONCLUSION In this multicenter, real-world cohort of children treated for 1st relapse in the immunotherapy era, suboptimal outcomes for early BM relapse persisted, with particularly dismal 4y OS of 29% for relapses <18m after diagnosis. In contrast, survival for late BM and isolated CNS relapses compared favorably to historic data. Only 1 in 5 patients initiated relapse therapy on a clinical trial and although 1st relapse is not an approved indication for commercial CART in pediatrics, 36% received CART. In an emulated trial of post-reinduction blina/HCT v CART, adjusted EFS and OS were comparable, suggesting that CART may be a viable alternative to HCT for select patients. Post hoc analyses will identify whether specific subgroups may benefit more from one strategy.

ABSTRACT The American College of Clinical Pharmacy (ACCP) first described the role and history of the pharmacist as principal investigator (PI) in 2000. An update was published in 2010, citing evidence from NIH and the ClinicalTrials.gov registry that showed an increase in the number of individuals with a Pharm.D. degree engaging in pharmacist‐directed research. The 2025 ACCP Publications Committee was charged with providing an update to the 2010 paper. Key findings include a substantial increase in the total amount of federal funding awarded to schools of pharmacy (SoP) between 2011 and 2023, a modest increase in the number of pharmacists receiving federal grants when comparing 2010 with 2024, and evidence of pharmacist leadership and engagement in Clinical and Translational Science Award networks and service on national grant review panels. It remains challenging, however, to ascertain accurate and reliable data on pharmacists serving in PI roles because of the limitations of currently available data sources. This is especially true for pharmacist PIs who receive non‐federal funding. Future opportunities include a continued emphasis on training programs to prepare pharmacists for PI roles, greater institutional support (e.g., research infrastructure, mentoring programs) for pharmacists serving in PI roles, better promotion of research career tracks to Pharm.D. students and trainees, enhanced efforts at SoP to pursue institutional training grants, and more collaborative efforts across professional organizations to advocate for pharmacist‐scientists. An urgent call to action is necessary to ensure the future growth and success of pharmacist‐directed research.

Abstract Description Neurons upregulate MHC Class I during infection and neuroinflammation associated with demyelinating diseases, allowing them to present both self and foreign antigens to CD8+ T cells. We hypothesized that ablation of neuronal MHC I expression reduces neural antigen-specific CD8+ T cell recruitment to demyelinated CNS and reduces neuron loss. We have previously shown that demyelination induces expression of MHC Class I on neurons and axons, allowing neuron-specific neoantigens to be presented to CD8+ T cells, leading to neuroinflammatory damage. Elevated MHC-I and β2-microglobulin expression in white and grey matter tissue from MS patients further supported the role of CD8+ T cells in neuronal injury. Here we demonstrate that neuron specific β2-microglobulin ablation in the B6 MOG35-55 EAE model of multiple sclerosis reduces disease progression and severity via clinical scoring. Our preliminary findings suggest that MHC-I ablation may reduce peripheral activation and CNS recruitment of neural antigen-specific CD8+ T cells as well as CD8+ T cell-mediated neurodegeneration in in the context of demyelinating disease. Future studies are aimed at generating a humanized mouse model reconstituted with patient immune cells to understand the role of MHC I expression in neurons, astrocytes, and oligodendrocytes. Specifically, using this model, we will characterize brain infiltrating T cells from patients with CNS autoimmune disease and suspected T cell involvement. Funding Sources Generous donation from Don and Fran Herdrich. Topic Categories Neuroimmunology (NEUR)

PURPOSE Neoadjuvant immune checkpoint inhibitors (nICIs) have demonstrated high response rates in deficient mismatch repair/microsatellite instability–high (dMMR/MSI-H) gastroesophageal adenocarcinoma (GEA). The NEONIPIGA and INFINITY trials demonstrated high rates of pathologic complete response (pCR) in this patient population. Furthermore, the INFINITY trial explored the feasibility of managing these patients nonoperatively, demonstrating promising results. This study aimed to evaluate clinical outcomes of nICIs in resectable dMMR/MSI-H GEA, with a focus on the feasibility of nonoperative management (NOM). MATERIALS AND METHODS This retrospective cohort study included patients with resectable dMMR/MSI-H GEA and treated with nICIs ± surgery at the Mayo Clinic. Patients were identified from institutional records, and clinical data were retrospectively reviewed. Primary outcomes were clinical complete response (cCR) and pCR. Secondary outcomes included event-free survival (EFS), radiologic complete response (rCR), and immune-related adverse events (irAEs). RESULTS A total of 26 patients treated between April 1, 2017, and July 30, 2025, were identified. Nine patients (34.6%) underwent surgery, of whom six (66.7%) achieved pCR. Seventeen patients (65.4%) pursued NOM, with 10 (71.4%) of 14 evaluable patients achieving cCR and 14 (82.4%) of 17 evaluable achieving rCR. One patient who initially achieved cCR had a local recurrence on surveillance endoscopy and underwent salvage endoscopic resection. At a median follow-up of 19.3 months, 15 (88.2%) of 17 patients in the NOM cohort were alive and metastasis-free, with EFS rates of 87.3% at 12 and 24 months for all patients. irAEs occurred in nine patients (34.6%), with no grade ≥3 toxicities. CONCLUSION In this retrospective cohort study, nICIs led to high cCR and pCR rates in resectable dMMR/MSI-H GEA, supporting the use of immune checkpoint inhibitors in this setting and the feasibility of NOM in select patients.