Parrondo, Ricardo D

Objective Systemic sclerosis (SSc) is an autoimmune disease marked by immune dysregulation, leading to progressive fibrosis and multiorgan dysfunction. Autologous hematopoietic cell transplantation (autoHCT) has demonstrated superiority over conventional immunosuppression in randomized trials yet remains underused in the United States. We report outcomes following implementation of autoHCT as a standard‐of‐care strategy at our institution. Methods We performed a retrospective analysis of consecutive patients with severe SSc undergoing autoHCT between April 1, 2020, and December 31, 2023. Eligibility required progressive disease despite standard immunosuppressive therapy. Primary endpoints were overall survival (OS) and event free survival (EFS). Secondary endpoints included cumulative incidence of relapse and nonrelapse mortality (NRM), organ‐specific outcomes, and transplant‐related complications. Results Twenty‐five patients underwent autoHCT. Median age was 46 years; 80% were female. At a median follow‐up of 23 (interquartile range 16.4–31.9) months, two‐year OS was 91.67% (95% confidence interval [CI] 81.25–100.0) and EFS was 74.51% (95% CI 58.78–94.45). Two‐year cumulative incidence of relapse was 23.93% (95% CI 4.27 –43.59), and NRM was 8.33% (95% CI 2.97–19.64). Significant improvement in Modified Rodnan Skin Score was observed at day +90 and +180 ( P < 0.05), whereas pulmonary function stabilized. Infectious complications occurred in 56% of patients, primarily viral reactivations. Conclusion Implementation of autoHCT for severe SSc in a multidisciplinary care model was associated with favorable survival and meaningful improvement in skin disease, with acceptable toxicity. Earlier referral and optimization of conditioning strategies may further reduce relapse and treatment‐related morbidity.

ABSTRACT Ciltacabtagene autoleucel (cilta‐cel) has demonstrated excellent efficacy and long‐term disease control in patients with relapsed/refractory multiple myeloma (RRMM). However, a proportion of patients experience early treatment failures. We investigated clinical factors associated with early progression or death (within 12 months) in patients with RRMM receiving standard‐of‐care cilta‐cel across the three Mayo clinic centers. Patients with a follow‐up of at least 12 months or progression or death within 12 months from infusion were included. Of the patients with early treatment failure ( n = 52), 69% had progressive disease and 31% had a non‐relapse mortality (NRM) event. In patients without early treatment failure ( n = 164), 13% of events were NRM. Among pretreatment factors, prior BCMA‐directed therapy, presence of extramedullary disease and a CAR‐HEMATOTOX score of ≥ 2 were independent predictors of early progression or death. The utilization of cilta‐cel in earlier lines of treatment (1–3 vs. 4 or more) demonstrated comparable PFS (12‐month PFS 73% vs. 77%, p = 0.94). Measurable residual disease positivity in the bone marrow at 3 months (11/197 patients) identified a small but high‐risk group with an increased risk of early treatment failure (OR 5.68; p = 0.012). Patients with less than a complete response on a FDG PET/CT at 3 months also had an increased risk of early treatment failure (OR 11.8; p < 0.0001). Our findings may help identify patients at high‐risk for early adverse outcomes despite receiving highly effective therapy, and support consideration of novel therapeutic strategies within a clinical trial setting.

e19094 Background: WM/LPL is an indolent B-cell Non-Hodgkin Lymphoma with prolonged survival and predisposition to secondary malignancies (SM) influencing clinical outcomes and survivorship care. We evaluated the incidence, demography, treatment utilization, and outcomes of SM in patients with WM/LPL using population-based data. Methods: SEER-22 database was used to identify patients with LPL/WM diagnosed between 2000–2022 and stratified by SM. Overall survival (OS) was analyzed using Kaplan–Meier survival analysis and propensity score matched Cox regression was used to assess mortality risk. Hazard ratios were reported, with p<0.05 deemed significant. Results: 22,170 patients with WM/LPL were identified, with a median age of 71 years (IQR 16); the cohort was predominantly male (59.0%), White (84.0%), had a median household income of $50,000–$75,000 (48.9%), and resided primarily in urban areas (89.5%). Among all WM/LPL patients, 20.8% (n=4,615) developed a SM. Patients who developed SM were older than those without (median age 75 vs 70 years, p<0.0001) with 45.2% alive at predefined follow-up. The most common solid organ SM were gastrointestinal adenocarcinoma (16%), prostate cancer (14%), and lung adenocarcinoma (9%), while the leading hematologic SM were plasma cell myeloma (6%), diffuse large B-cell lymphoma (5%), and myelodysplastic syndrome (2%). 35.3% of the cohort received chemotherapy, while 0.1% received cancer-related surgery or radiation. On multivariable analysis, older age (OR 0.82, 95% CI 0.81–0.83), male sex (OR 0.59, 95% CI 0.44–0.80), urban residence (OR 1.99, 95% CI 1.24–3.18), and higher income (OR 2.16, 95% CI 1.13–4.15) were significantly associated with SM diagnosis. Kaplan–Meier analysis demonstrated inferior survival among patients with SM (54.8% vs 45.2%, p<0.0001), with shorter median OS (9 vs 14 years, log-rank p<0.001). Similarly, Propensity-matched analysis revealed worse OS in patients with SM (HR 1.15, 95% CI 1.09–1.22, p<0.001). Median OS varied substantially by SM site (see Table). Conclusions: Our study demonstrates a substantial burden of SMs among patients with WM/LPL and are associated with substantially inferior survival despite the indolent nature of the disease. The marked heterogeneity in SM types and outcomes highlights the need for risk-adapted surveillance, survivorship-focused care, and equitable strategies to address disparities and improve long-term outcomes in this population. SM Site Median OS (years) IQR p-value Hepatopancreatobiliary 1 0 <0.05 CNS 3.5 9 <0.05 Breast 3 6 <0.05 Colorectal 4 3.5 <0.05 Lymph Node 5 8 <0.05 Blood 6 7 <0.05 Lung 7 9 <0.05 Head & Neck 6.5 8.5 <0.05 Melanoma 9 10 <0.05 Urogenital 10.5 7 <0.05

e15708 Background: AFTT is characterized by physical, nutritional, and psychosocial decline. In GIC, AFTT arises from malnutrition, disease progression, or treatment-related toxicity resulting in poor quality of life. We evaluated the association between AFTT and IM, length of stay (LOS), and hospital charges (HC) in hospitalized GIC patients. Methods: The National Inpatient Sample (2016-21) was used to identify adult hospitalizations with GIC using ICD-10 codes, which were stratified as primary or secondary diagnoses by AFTT. Clinical characteristics and primary outcomes including IM, LOS, and HC were extracted. Multivariable regression models adjusting for demographics, insurance, comorbidity burden, census tract income, and hospital teaching status were evaluated. Results: Among 2,732,505 GIC hospitalizations, colorectal (46.9%) and pancreatic (20.4%) cancer predominated; 121,035 (4.4%) had AFTT. Patients with AFTT vs non-AFTT, were older (mean = 69.3 vs 66.5 yrs), more often male (58.1% vs 57%), and from the lowest income quartile (27.7% vs 26%). AFTT cohort had higher comorbidity burden (mean CCI = 7.24 vs 6.26), more Black patients (19.1% vs 12.8%), higher Medicare use (62.7% vs 56.0%), increased palliative care consultation (37.4% vs 13.6%), risk of malnutrition, AKI, and dementia (all p< 0.001). AFTT was associated with higher IM, longer LOS, and lower HC. Higher age, males, and self-pay were associated with increased IM and HC, but shorter LOS. Lower CCI was associated with reduced IM, LOS, HC, whereas urban hospitals showed lower IM but higher LOS and HC. Black patients had higher IM and LOS but lower HC, contrary to Hispanic patients. Conclusions: The grave impact of AFTT and variability in survival and practice patterns is driven multifactorially, raising concerns about inequitable care access and differences in healthcare utilization. Standardized guidelines and multidisciplinary interventions are urgently needed to combat AFTT in GIC. Predictor IM aOR (95% CI) LOS Adj. Ratio (95% CI) HC Adj. Ratio (95% CI) AFTT Status (vs. Non-AFTT) 1.96 (1.93-2.00) 1.13 (1.12-1.14) 0.86 (0.85-0.86) Age (/year increase) 1.02 (1.02-1.02) 1.00 (1.00-1.00) 1.00 (1.00-1.00) Sex (vs. Female) Male 1.18 (1.17-1.19) 0.99 (0.98-0.99) 1.05 (1.05-1.06) CCI Score (vs. High, ≥5) Low (≤2) Mid (3-4) 0.33 (0.32-0.33) 0.48 (0.47 - 0.48) 0.87 (0.87 - 0.88) 0.93 (0.93 - 0.94) 0.93 (0.93 - 0.94) 1.02 (1.02 - 1.02) Insurance (vs. Medicare) Private Medicaid Self-Pay 1.03 (1.01 - 1.05) Ref in model 1.29 (1.24 - 1.33) 0.92 (0.91 - 0.92) 0.96 (0.95 - 0.97) 0.98 (0.97 - 1.00) 1.03 (1.02 - 1.03) 1.06 (1.05 - 1.06) 0.96 (0.95 - 0.97) Race (vs. White) Black 1.03 (1.00 - 1.06) 1.07 (1.06 - 1.08) 0.95 (0.94 - 0.96) Facility Status (vs. Rural) Urban Non-Teaching Urban Teaching 0.87 (0.85 - 0.89) 0.78 (0.77 - 0.80) 1.10 (1.09 - 1.11) 1.18 (1.17 - 1.19) 1.64 (1.63 - 1.65) 1.86 (1.84 - 1.87)

e14111 Background: Primary CNSL (PCNSL) is a rare, aggressive B-cell non-Hodgkin lymphoma limited to the CNS, while secondary CNSL (SCNSL) represents CNS involvement from systemic lymphoma. Previous observations focused on CNSL have limited data clinically comparing PSNSL and SCNSL. We aimed to evaluate overall survival and associated factors in patients with PCNSL vs SCNSL using a large population database. Methods: We conducted a retrospective cohort study using the SEER-22 database to identify patients diagnosed with CNSL between 2020-2022. Group comparisons used t-tests or ANOVA for continuous variables, chi-square tests for categorical variables, and Kaplan–Meier survival analysis, with all analyses performed in RStudio 4.1.1 and significance deemed as p<0.05. Results: 14,964 patients with CNS lymphoma were identified, with 84.6% PCNSL and 15.4% SCNSL cases. The overall median age was 65 years (IQR 20), with 52% male, 66% White patients, residing in urban areas (90%) and median household income of $50,000–$75,000 (52%). Compared with PCNSL, patients with SCNSL were significantly older (72 vs 64 years, p<0.0001). SCNSL more frequently involved the cerebrum (39% vs 34%) and cerebellum (5.5% vs 4.5%), but less commonly affected the nerves (12.0% vs 12.5%) and spinal cord (4.2% vs 5.1%) (p<0.05). Disease was predominantly unilateral (95.8%) in both groups. Chemotherapy (55% vs 56%) and radiotherapy (19% vs 18%) utilization did not differ significantly, with external beam radiation comprising 94.3% of radiated cases. PCNSL patients were more likely to undergo surgical intervention than SCNSL patients (31.8% vs 28.7%; p=0.0027). Diffuse large B-cell lymphoma was the most common histologic subtype in both PCNSL (70.1%) and SCNSL (74.3%). Median overall survival was shorter in SCNSL (1.64 years) than PCNSL (1.99 years). Survival improved significantly across diagnostic eras (2000–2005 to 2016–2020; log-rank p<0.001), while lower income (<$50,000) and rural residence were associated with inferior outcomes (p=0.028 and p=0.033). Conclusions: Survival in CNS lymphoma remains poor, with SCNSL associated with worse outcomes compared with PCNSL. Greater understanding of treatment variation and disease differences is needed to optimize therapy and improve patient outcomes. Characteristic PCNSL SCNSL Total p-Value N 12667 2297 14964 Population Distribution 0.033 Urban 11426 2038 13464 Rural 1241 259 1500 Surgery 0.0027 Yes 3630 730 4360 No 9037 1567 10604 Months from Diagnosis to Rx(Mean, SD) 0.31 (0.86) 0.27 (0.65) 0.30 (0.83) 0.0077 Death Status <0.0001 Dead 8603 1772 10375 Alive 4064 525 4589 Overall Survival (in years, Mean, SD) 1.99 (2.85) 1.64 (2.31) 1.93 (2.77) <0.0001

7543 Background: Delayed neurotoxicity (DNT) after ciltacabtagene autoleucel (cilta-cel) is associated with severe morbidity and mortality occurring in 10-15% of patients. A high post-infusion peak absolute lymphocyte count (ALCpeak ≥3x10 9 /L; ALC hi ) is correlated with an increased risk of DNT (25-30%). We previously examined prophylactic dexamethasone (PPX DEX) administered for 3 days when ALC hi was reached and found no reduction in ALC expansion, DNT incidence or severity. Here, we report the use of prophylactic cyclophosphamide (PPX CTX) on ALC kinetics and DNT. Methods: We conducted a retrospective analysis of patients (pts) treated with cilta-cel at Mayo Clinic (09-12/2025; n =60). Pts with ALC hi received CTX 500 mg IV/PO once (n = 22). Outcomes and ALC kinetics including ALCpeak, ALC D28 (ALC D28 ), and area under the curve D1-D28 (ALC AUC ) were compared with PPX DEX cohort (12/2024-08/2025; n =50) and a historical cohort without PPX (04/2022-11/2024; n =116). Results: Pre-lymphodepletion (LD) demographics were similar across historical ALC hi , PPX DEX, and PPX CTX groups. Pre-LD CRP was higher in the historical ALC hi cohort; however, baseline ferritin, CRS, and ICANS, and disease burden did not differ significantly between groups. There were no statistically significant differences in time to ALCpeak or ALC kinetics among the 3 cohorts. Among pts with ALC < 3×10⁹/L treated during the PPX CTX study period, 2 developed cranial nerve palsy (IEC-CNP; 2/38, 5%). Both presented with unilateral facial nerve palsy and were treated with corticosteroids. One pt resolved symptoms by one month, while the second had persistent symptoms at 2 weeks and remains on follow-up. Among ALC hi patients in the PPX CTX cohort, DNT occurred in 4/22 pts (18%), including 1 case of IEC-CNP (5%) and 3 with parkinsonism (IEC-PKS, 14%). Within the PPX CTX cohort, baseline characteristics and post-infusion CRS or laboratory parameters did not differ between patients with and without DNT. Among patients who developed DNT, ALC kinetics were similar across PPX CTX, PPX DEX, and historical cohorts. PPX CTX was well tolerated, with 2 cases of grade 1 nausea reported. The incidence of DNT did not differ significantly between the PPX DEX (14/61, 23%) and PPX CTX (4/22, 18%) cohorts. However, DNT presentations in the PPX CTX cohort appeared milder and were responsive to treatment. Two of three patients (67%) presented with mild symptoms (one with dynamic dysphasia; second with flat affect) that responded to DEX. A third patient presented with typical parkinsonian features (hypomimia, bradykinesia, rigidity) and demonstrated clinical improvement following high-dose CTX. Conclusions: PPX CTX was well tolerated. While it did not significantly impact ALC expansion kinetics or DNT rates, first few cases of IEC-PKS suggest that the presentation may be milder and amenable to less toxic treatment. Larger cohorts are needed to refine optimal prophylactic strategies.

Abstract Solitary bone plasmacytoma (SBP) and SBP with minimal marrow involvement (SBPmm) are treated similarly with definitive radiation therapy (RT) followed by observation. However, differences in the natural disease course after RT between the two, are not well described. We performed a multicenter study assessing outcomes after RT in 141 patients with SBP and 102 with SBPmm diagnosed between January 2010 and December 2024. About 92% of patients with SBPmm progressed to multiple myeloma (MM) vs 76% of those with SBP (P = .01). Among patients with SBP, 21% progressed with a second solitary bone lesion vs 4% with SBPmm (P&lt; .01). Patients with longer time to progression (TTP) after initial RT could achieve durable responses with RT to a second solitary plasmacytoma in the absence of other myeloma-defining events (MDE). Multifocal lytic bone lesions were the most common MDE, occurring in 89% and 81% of patients with SBPmm and SBP, respectively. Patients with SBPmm had a median TTP of 15 months (95% confidence interval [CI], 14-21) compared to 43 months (95% CI, 34-55) for those with SBP (P&lt; .0001); 67% with SBPmm progressed within 2 years of diagnosis. Del(17p) and 1q+ (gain or amplification) were associated with shorter TTP to MM in SBPmm, with 2-year progression rates of 100% and 82%, respectively. We report significant differences in risk and modes of progression between SBP and SBPmm. Patients with SBPmm are at particularly high risk for early progression to MM, with most developing bone disease as the MDE. These findings support prospective studies incorporating frontline systemic therapy for SBPmm.

Abstract Immune effector cell–associated enterocolitis (IEC-EC) has been observed after ciltacabtagene autoleucel (cilta-cel [Carvykti]) chimeric antigen receptor T-cell (CAR-T) therapy. It is associated with dismal outcomes and is poorly characterized. Here, we examined its clinical features, risk factors, and proposed management strategies. Among the 229 consecutive patients who received cilta-cel at Mayo Clinic, 9 (3.9%) presented with a nonresolving, nonbloody, grade 3 diarrhea, often requiring prolonged total parenteral nutrition. Gastrointestinal coinfections were seen in most patients. Median time from CAR-T infusion to symptom onset was 85 days (range, 35-166), and there appeared to be a latency from symptom onset to endoscopic evaluation. Histopathology findings resembling a graft-versus-host disease pattern of mucosal injury were most seen on duodenal biopsies, whereas 2 cases had patterns akin to a T-cell lymphoproliferative disorder (1 CD4+ and 1 CD8+). Independent associated factors for IEC-EC included high-risk disease as defined by the International Myeloma Society and International Myeloma Working Group, prolonged cytokine release syndrome, and antecedent delayed neurotoxicity. Response to first-line therapy comprising IV or oral corticosteroids, bile acid sequestrants, IV immunoglobulin, and antimicrobial-directed therapy was poor, with no durable responses. Biologic therapy appeared to induce durable responses in 3 of the 5 patients (2/2 vedolizumab; 1/3 infliximab); none of the responders had gastrointestinal coinfection. Early gastroenterology input for endoscopic evaluation with the inclusion of duodenal biopsy is a key component for diagnosis. Early institution of biologic therapy after failure of a short course of corticosteroids should be considered.

Abstract Large Language Models (LLM) are being widely adopted into the medical field for their impressive ability to analyze and summarize large amounts of text data. These models enable clinicians and researchers to extract meaningful insights from complex datasets and may assist with decision making. Here we present our workflows and application of LLM for the interpretation and summarization of clinical data related to CAR-T cell therapy. Using an LLM (Gemini 2.5 pro) in the Google Cloud Computing (GCP) environment, two applications were developed to analyze CAR-T cell therapy clinical data: 1) extracting and summarizing CRS and ICANS event-related data to streamline the compliance team workflow, and 2) identifying features available at time of CAR-T infusion able to classify patients into high- or low-monitoring needs 14 days post CAR-T. Patient data (vitals, labs, hematology notes, and EKGs) were extracted from the electronic medical record (EMR) using Google BigQuery into SQL tables in GCP. For each application, relevant data fields were retrieved, formatted into JSON objects, and embedded in the LLM prompt for context-aware processing. Both applications have undergone iterative prompt engineering after analyzing the LLM output against ground truth data in the EMR. For the application extracting and summarizing CRS and ICANS events, the LLM was optimized on Mayo Clinic Rochester data. When compared to the IEC compliance database, the LLM achieved 100% accuracy and F1 score for CRS events, and 96% accuracy and 82% F1 score for ICANS events. The match rate for CRS and ICANS grades were 83% and 89% respectively. We applied the same LLM to Mayo Clinic Arizona (MCA) and Mayo Clinic Florida (MCF) cases, who document clinical notes and toxicity flowsheet differently, and achieved an accuracy (MCA: 93%, MCF:93%) and F1 score (MCA: 96%, MCF: 96%) for CRS and accuracy (MCA: 81%, MCF:82%) and F1 score (MCA: 76%, MCF: 75%) for ICANS. LLM was able to capture events missed by manual reviews. For most of the discrepancies where compliance team final adjudication is needed, LLM will be updated to flag discrepancies for review by the compliance team. For the application related to the monitoring needs 14 days post CAR-T, the LLM identified 5 categories predictive of high or low monitoring needs post CAR-T infusion (disease status, inflammatory and tumor burden markers, hematologic status, renal function and performance status). Our model achieved a sensitivity of 85.7%, specificity of 23.8%, and F1 score of 65.5% for our first cohort, compared with data extracted by the LLM from the EMR. For our second cohort, with demographics statistically similar to cohort 1 and using the same 5 categories, the LLM achieved a sensitivity of 83.3%, a specificity of 28.6%, and F1 score of 65.4%. Our workflow and applications of LLM’s provide examples and guidance to others interested in applying LLM’s for clinical and research applications. Citation Format: Emmanuel Contreras Guzman, Matthew Jankowski, Andre De Menezes Silva Corraes, Malvika Gupta, Monica L. Shaw, Madiha Iqbal, Talal Hilal, Saurabh Chhabra, Ricardo Daniel Parrondo, Jody K. Mclean, Kim R. Riester, Kayla Joseph, Melinda Tan, Holly Ross, Cleyonia Barnett, Sylvia Carter, Semy Girmay, Rachel Wolan, Milana Ramsey, Christian Downhour, Kristy Morgan, Shae Sibley, Erica Rushing, Lucy Holmes, Allison Burgstahler, Stephen M. Ansell, Hassan Alkhateeb, Matthew Hathcock, Ramona Bruno, Allison C. Rosenthal, Hemant Murthy, Patrick B. Johnston, Jonas Paludo, Yi Lin. Applications of large language models to CAR-T cell therapy clinical data using Google cloud computing [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2026; Part 1 (Regular Abstracts); 2026 Apr 17-22; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2026;86(7 Suppl):Abstract nr 2740.