Chandani, Kanishka Uttam

8597 Background: Lorlatinib improves outcomes in NSCLC but commonly causes marked hyperlipidemia, prompting initiation of lipid-lowering therapy (LLT). Beyond lipid control, LLT may be associated with vascular events; however, its association with thromboembolism, healthcare utilization, and mortality among lorlatinib-treated patients has not been characterized in real-world cohorts. Methods: Using TriNetX, we identified adults with NSCLC who received lorlatinib (index = first lorlatinib record). Patients were grouped by early LLT initiation within 30 days of index versus no LLT within 30 days. LLT included statins, ezetimibe, PCSK9 inhibitors, or fibrates. Cohorts were balanced 1:1 using propensity score matching on demographics and baseline comorbidities. Outcomes were assessed through 365 days; patients with prior outcome documentation were excluded. Results: After matching, 387 patients per cohort were analyzed. Early LLT was associated with lower all-cause mortality at 365 days (16.1% vs 26.4%; risk ratio [RR] 0.61, 95% CI 0.46-0.81; p=0.0004) and improved time to death (hazard ratio 0.60, 95% CI 0.44-0.82). Early LLT was also associated with lower venous thromboembolism (6.2% vs 12.1%; RR 0.51, 95% CI 0.30-0.86; p=0.0093) and fewer inpatient hospitalizations (14.6% vs 23.6%; RR 0.62, 95% CI 0.40-0.97; p=0.0320). Emergency department visits were numerically lower (8.3% vs 13.9%; RR 0.59, 95% CI 0.35-1.00; p=0.0467). No significant differences were observed for acute kidney injury or major adverse cardiovascular events. Conclusions: In a real-world propensity-matched cohort of lorlatinib-treated NSCLC patients, LLT initiated within 30 days was associated with lower 1-year mortality, venous thromboembolism, and hospitalization. Given the frequency of lorlatinib-associated dyslipidemia, these findings support early lipid monitoring and timely LLT initiation in practice. Prospective studies are warranted to confirm these associations. 365-day outcomes after matching. Outcome Early LLT (n=387) No early LLT (n=387) RR (95% CI) HR (95% CI) p All-cause mortality 16.1% 26.4% 0.608 (0.458-0.806) 0.597 (0.435-0.818) 0.0004; log-rank 0.001 Venous thromboembolism 6.2% 12.1% 0.509 (0.302-0.857) — 0.0093 Inpatient hospitalization 14.6% 23.6% 0.619 (0.396-0.967) — 0.0320 ED visit 8.3% 13.9% 0.593 (0.352-1.001) — 0.0467 Acute kidney injury 5.4% 7.1% 0.769 (0.429-1.378) — 0.3758 MACE 4.6% 4.6% 1.006 (0.511-1.979) — 0.9868

7041 Background: CD20×CD3 bispecific antibodies and CD19-directed CAR T-cell therapies are increasingly used in relapsed/refractory DLBCL. CAR T therapy is associated with higher rates of CRS,ICANS, and cytopenias, whereas bispecific antibodies are often perceived as less toxic and more outpatient-friendly. Methods: We conducted a retrospective cohort study using the TriNetX Global Collaborative Network. Adult patients with DLBCL treated with bispecific antibodies (glofitamab, epcoritamab) were compared with those receiving commercial CAR T-cell therapy (tisa, liso, axi). Propensity score matching was performed on demographics, comorbidities, baseline laboratory values, and corticosteroid exposure, yielding 468 patients per cohort. Outcomes included CRS, ICANS, severe neutropenia (ANC <500/µL), and thrombocytopenia (platelets <50×10³/µL), as well as hospitalization and ICU admission at 1, 3, 6, and 12 months. Overall survival (OS) was assessed using Kaplan–Meier analysis with log-rank testing. Results: After matching, CAR T therapy was associated with significantly higher immune-mediated toxicity. CRS occurred more frequently with CAR T at 1 month (37.4% vs 22.4%), 3 months (39.3% vs 27.6%), 6 months (40.6% vs 28.8%), and 12 months (41.2% vs 29.7%) (all p<0.001). ICANS was also more common with CAR T across all timepoints (1 month: 10.5% vs 4.9%; 12 months: 12.6% vs 7.5%). Severe neutropenia and thrombocytopenia were markedly more frequent in the CAR T cohort, with neutropenia affecting 66.7% vs 12.8% at 1 month and 71.6% vs 32.7% at 12 months (all p<0.001). Despite higher toxicity, healthcare utilization was comparable. Hospitalization rates were similar between groups at 1 and 3 months (61.8% vs 66.7% and 67.1% vs 75.9%), and ICU admission rates did not differ meaningfully at any timepoint. Importantly, overall survival consistently favored CAR T therapy. Survival differences emerged early and persisted over time, with lower mortality in the CAR T cohort at 1 month (2.1% vs 9.0%), 3 months (7.7% vs 18.6%), 6 months (15.8% vs 26.7%), and 12 months (26.5% vs 35.3%), corresponding to significantly improved OS by log-rank testing at all timepoints (p<0.001). Conclusions: In this large, real-world, propensity-matched analysis of relapsed/refractory DLBCL, CAR T-cell therapy was associated with substantially higher rates of CRS, ICANS, and severe cytopenias compared with bispecific antibodies. However, these toxicities did not translate into higher hospitalization or ICU utilization. Despite a less favorable early toxicity profile, CAR T therapy conferred a consistent and clinically meaningful survival advantage from early to late follow-up. Early toxicity alone should not preclude CAR T referral in appropriate candidates, underscoring the need for optimized patient selection, sequencing strategies, and supportive care.

5079 Background: Treatment sequencing in metastatic castration-resistant prostate cancer (mCRPC) after ADT and ARPI exposure varies in practice. While 177 Lu-PSMA use is expanding in routine practice, real world head to head comparisons with docetaxel in ARPI-exposed mCRPC are limited, particularly for short-term outcomes and treatment related acute care utilization. Methods: Using TriNetX, adults > 18 years of age with metastatic prostate cancer and prior ARPI exposure who initiated 177 Lu-PSMA or docetaxel were identified (index = first administration). Cohorts were balanced with 1:1 propensity score matching (PSM) on demographics and baseline comorbidities. Outcomes from day 1–180 post-index included all-cause mortality (primary), hospitalization, acute kidney injury (AKI; ICD-10 N17), and thromboembolic/ischemic events (ICD-10 I21/I26/I63/I82). For each outcome, patients with prior documentation of that outcome were excluded. Outcomes are reported as risks and risk ratios (RR) with 95% confidence intervals. Results: Before matching, 563 patients initiated 177 Lu-PSMA-617 and 8,749 initiated docetaxel; after 1:1 PSM, 497 patients per cohort were analyzed. At 180 days, all-cause mortality was 7.3% (36/494) with 177 Lu-PSMA-617 versus 12.2% (60/491) with docetaxel (RR 0.60, 95% CI 0.40–0.88). Hospitalization occurred in 7.2% (21/290) versus 21.1% (52/247) (RR 0.34, 95% CI 0.21–0.55). In a separate matched renal-safety analysis (480 per cohort), AKI occurred in 2.8% (11/390) versus 9.0% (36/399) (RR 0.31, 95% CI 0.16–0.60). Thromboembolic/ischemic events were 3.8% (15/394) versus 6.4% (26/404) (RR 0.59, 95% CI 0.32–1.10). Conclusions: In ARPI-exposed mCRPC, 177 Lu-PSMA was associated with lower 180-day mortality risk and substantially fewer hospitalizations than docetaxel, with a lower risk of AKI. These findings highlight a potential short-term effectiveness and acute-care utilization advantage of 177 Lu-PSMA in routine practice and support further prospective evaluation. Key 180-day outcomes after matching. Outcome 177 Lu-PSMA Docetaxel Effect estimate (180 days) All-cause mortality 36/494 (7.3%) 60/491 (12.2%) RR 0.596 (0.402-0.884) Hospitalization 21/290 (7.2%) 52/247 (21.1%) RR 0.344 (0.213-0.554); Acute kidney injury (AKI)* 11/390 (2.8%) 36/399 (9.0%) RR 0.312 (0.163-0.595) Thromboembolic/ischemic† 15/394 (3.8%) 26/404 (6.4%) RR 0.592 (0.318-1.100) *AKI analysis used a separate matched run (480 per cohort). †Composite of I21, I26, I63, I82.

Chimeric antigen receptor (CAR)-based therapies have become an integral part of modern cancer care, delivering durable responses in patients with otherwise refractory hematologic malignancies. As their use has expanded, it has become increasingly clear that these immune-based treatments exert important effects on the cardiovascular system. Rather than reflecting isolated cardiac injury, CAR-associated cardiovascular complications arise from a broader inflammatory process in which immune activation, cytokine release, endothelial dysfunction, and myocardial stress are closely interconnected. Pro-inflammatory mediators such as interleukin-6, interleukin-1β, tumor necrosis factor-α, and interferon-γ play central roles in shaping these responses, particularly during cytokine release syndrome. From a clinical perspective, cardiovascular manifestations often include hypotension, arrhythmias, and transient reductions in left ventricular function, with more severe presentations occurring in patients who develop high-grade inflammatory toxicity. At the same time, advances in immune engineering are reshaping how these platforms are viewed, extending their relevance beyond toxicity alone. Preclinical studies now suggest that CAR-based approaches may be adapted to modulate cardiac fibrosis and promote myocardial repair, highlighting a potential shift from purely oncologic applications toward broader cardiovascular benefit. Placing these developments within a cardio-oncology framework emphasizes the need for careful cardiovascular assessment, longitudinal monitoring, and close collaboration between specialties.

The therapeutic landscape of hematologic malignancies has undergone a paradigm shift with the increasing incorporation of targeted therapies, including inhibitors of vascular endothelial growth factor (VEGF) signaling. While VEGF-directed agents have historically been developed and deployed in solid tumors, their application in hematologic cancers—particularly multiple myeloma, select leukemias, and rare lymphomas—has expanded in investigational and clinical settings. VEGF is fundamental to angiogenesis, maintenance of endothelial integrity, and regulation of vascular tone. As a result, therapeutic inhibition of VEGF signaling is associated with a characteristic spectrum of cardiovascular adverse effects. These include hypertension, endothelial dysfunction, heart failure, thromboembolic complications, and renal injury, all of which present important clinical challenges in patients with hematologic malignancies. This population frequently has additional vulnerability due to factors such as cytopenias, preexisting renal impairment, and prior exposure to cardiotoxic anticancer therapies. This review aims to provide a cardio-oncology–oriented overview of VEGF biology, the range of VEGF-targeted agents used in hematologic cancers, and the underlying mechanisms driving their cardiovascular toxicities.

Advances in cancer therapeutics have substantially improved survival across multiple malignancies but have concurrently increased the burden of cancer therapy–related cardiovascular toxicity, establishing cardio-oncology as an essential discipline situated at the interface of oncology and cardiovascular medicine. Despite growing incorporation of cardiac imaging and circulating cardiac biomarkers into surveillance strategies, current approaches remain limited by modest specificity, heterogeneous risk profiles, and inconsistent translation into effective cardioprotective interventions. This review synthesizes contemporary evidence on the biological mechanisms underlying cancer therapy–related cardiovascular toxicity and critically evaluates the current role and limitations of established cardiac biomarkers, including high-sensitivity cardiac troponins and natriuretic peptides, in risk stratification and early injury detection. We further examine why many cardioprotective clinical trials have yielded neutral or modest results, highlighting signal dilution arising from low-risk populations, endpoint heterogeneity, and timing mismatches between injury biology and intervention. This review advances a precision cardio-oncology framework by integrating tumor-derived liquid biopsy platforms—such as circulating tumor DNA, tissue-specific cell-free DNA, and extracellular vesicles—with cardiac biomarkers to provide a biologically contextualized assessment of cardiovascular risk. Tumor-derived biomarkers may reflect treatment intensity, systemic inflammatory burden, and cardiotoxic susceptibility, thereby enhancing the interpretation of cardiac biomarker signals and refining patient selection for targeted cardioprotective strategies.

Abstract Background Thrombotic Thrombocytopenic Purpura (TTP) is a rare, typically acquired disorder due to an immune-mediated deficiency of ADAMTS13, a metalloprotease responsible for cleaving large multimers of von Willebrand Factor (vWF). In the absence of ADAMTS13 activity, ultra-large vWF multimers accumulate, promoting widespread platelet aggregation and microvascular thrombosis. This consumptive cascade leads to thrombocytopenia, microangiopathic hemolytic anemia, fever, neurological symptoms, and rarely renal dysfunction. Although therapeutic plasma exchange (TPE) has long been the cornerstone of TTP treatment, the FDA approved Caplacizumab as a first-line treatment for TTP in 2019. This drug is a bivalent single-domain antibody that binds to the A1 domain of vWF and prevents its interaction with platelets, thus effectively interrupting the pathogenic cascade, which is associated with a risk of bleeding. Methods We conducted a retrospective cohort study using the TriNetX Global Collaborative Network, comprising data from 152 healthcare organizations. Adults (≥18 years) with a diagnosis of TTP who received Caplacizumab plus TPE were compared to patients with TTP who received TPE alone. 1:1 propensity score matching (PSM) was performed to balance characteristics between cohorts. The primary outcomes assessed were all-cause mortality and major bleeding events over a period of 1 month. Results A total of 4084 patients with TTP were identified, of whom 356 received caplacizumab with TPE and 3728 received TPE. After PSM, 2 balanced cohorts were created: C+P (Caplacizumab + TPE), P only (TPE), each comprising 356 patients. The average age in C+P and P only, after PSM, was 50.4 +/- 16.2 and 50.8 +/- 16.2 years, respectively. Females formed 65.7% of both C+P and P only, and males accounted for 28.4% and 28.7% of C+P and P only, respectively. 2.8% patients in C+P and 7.06% patients in P only had all-cause mortality at the end of 1 month. One-month all-cause mortality was significantly lower in C+P (2.8%) compared to P only (7.06%), with an odds ratio (OR) of 0.385 (95% CI 0.182 to 0.814, p=0.010). Upon assessment of bleeding outcomes, no statistically significant risk difference was noted between the 2 groups, with the odds ratio being 0.974 (95% CI 0.399 to 2.379, p=0.954). Conclusion Our large database study suggests that the addition of caplacizumab to standard TPE therapy is associated with a reduction in one-month all-cause mortality in patients with TTP, without a corresponding increase in major bleeding. However, given the lack of granular clinical data, such as contraindications to caplacizumab use, it is possible that patients who received TPE alone were inherently at a higher risk. As such, while these findings support the potential benefit of early caplacizumab use, they should be interpreted with caution and warrant prospective validation to confirm causality and assess long-term outcomes.

Abstract Background: Patients with myelodysplastic syndromes (MDS) are at heightened risk for severe infections, including sepsis, due to underlying cytopenias and immune dysregulation. Hospital-level characteristics, including size and available resources, may influence clinical outcomes in these patients, but data remain limited. This study examines the association between hospital bed size and sepsis-related complications in patients with MDS using a nationally representative dataset. Methods: We conducted a retrospective cohort analysis using the National Inpatient Sample (NIS) from 2016 to 2022, identifying adult hospitalizations with co-diagnoses of MDS and sepsis. Hospitalizations were stratified by hospital bed size: small (n = 15,490), medium (n = 22,815), and large (n = 40,245). Multivariable logistic regression, adjusted for patient demographics, comorbidities, and hospital characteristics, was used to assess associations between hospital bed size and eight clinical outcomes: in-hospital mortality, septic shock, acute renal failure, respiratory failure, encephalopathy, disseminated intravascular coagulation (DIC), Clostridioides difficile infection (CDI), and fungal sepsis. Results: Compared to small hospitals, patients treated at large hospitals had significantly higher odds of in-hospital mortality (OR 1.43, p &lt; 0.001), septic shock (OR 1.25, p &lt; 0.001), acute renal failure (OR 1.10, p &lt; 0.001), encephalopathy (OR 1.11, p = 0.004), DIC (OR 1.48, p = 0.007), and fungal sepsis (OR 2.13, p = 0.028). Medium-sized hospitals were also associated with increased odds of mortality (OR 1.16, p = 0.021) and septic shock (OR 1.13, p = 0.038). No statistically significant differences were found in rates of CDI across hospital sizes. Respiratory failure showed a borderline association in medium hospitals (OR 1.05, p = 0.082) but not in large hospitals. Conclusion: Hospital bed size is independently associated with important variations in sepsis-related outcomes among patients with MDS. Large hospitals demonstrated significantly increased odds of multiple complications and mortality, possibly reflecting referral bias, higher disease acuity, or institutional coding practices. These findings underscore the importance of hospital-level factors in evaluating outcomes and resource planning for high-risk hematologic populations. Keywords: Myelodysplastic syndromes, hospital bed size, sepsis, mortality, ICU complications, NIS

Abstract Background: Myelodysplastic syndromes (MDS) are a heterogeneous group of clonal hematopoietic disorders often complicated by infections due to cytopenias. Sepsis is a frequent cause of hospitalization and mortality in MDS patients. Neutropenia, a common feature in MDS, may predispose patients to specific infectious complications, but its impact on sepsis-related outcomes remains poorly characterized. Methods: We conducted a retrospective cohort study using the National Inpatient Sample (NIS) database from 2016 to 2022. Adult hospitalizations with co-diagnoses of MDS and sepsis were identified using ICD-10-CM codes. Patients were stratified based on the presence or absence of neutropenia. Multivariable logistic regression models were used to evaluate the association between neutropenia and specific in-hospital outcomes, including Clostridioides difficile infection, fungal sepsis, and disseminated intravascular coagulation (DIC). Models were adjusted for age, sex, comorbidities, hospital characteristics, and illness severity. Results: A total of 78,549 hospitalizations involving MDS patients with sepsis were identified, including 11,295 (14.4%) with neutropenia. Neutropenic patients had significantly higher odds of C. difficile infection (adjusted odds ratio [aOR] 1.61, 95% CI 1.30–1.99, p &lt; 0.001) and fungal sepsis (aOR 2.08, 95% CI 1.22–3.54, p = 0.007) compared to those without neutropenia. However, neutropenia was not significantly associated with DIC (aOR 0.84, 95% CI 0.59–1.19, p = 0.322). Conclusion: In this large national cohort, neutropenia was associated with a significantly increased risk of C. difficile infection and fungal sepsis among MDS patients hospitalized with sepsis. These findings highlight the need for early recognition and targeted antimicrobial strategies in neutropenic MDS patients. No significant association was observed between neutropenia and DIC. Future studies should explore preventive strategies and risk stratification tools tailored to this high-risk population. Keywords: Myelodysplastic syndromes, neutropenia, sepsis, NIS, Clostridioides difficile, fungal sepsis, outcomes

Abstract Background: Myelodysplastic syndromes (MDS) are clonal hematopoietic disorders characterized by ineffective hematopoiesis, cytopenias, and an increased susceptibility to infections. Sepsis remains a common and serious cause of morbidity and mortality in this population. While racial disparities in sepsis-related outcomes have been described in the general population, their presence and magnitude among patients with MDS remain poorly understood. Methods: We performed a retrospective cohort study using the National Inpatient Sample (NIS) from 2016 to 2022 to identify adult hospitalizations with co-diagnoses of MDS and sepsis. Patients were stratified by race into White (reference), Black, Hispanic, Asian, Native American, and Other categories. Multivariable logistic regression models, adjusted for demographics, comorbidities, and hospital characteristics, were used to evaluate associations between race and seven key sepsis-related complications: septic shock, acute renal failure, respiratory failure, encephalopathy, disseminated intravascular coagulation (DIC), Clostridioides difficile infection (CDI), and fungal sepsis. Results: Among 78,549 hospitalizations for MDS with sepsis, significant racial disparities were observed. Asian patients had higher odds of developing septic shock (OR 1.26, 95% CI 1.05–1.50, p = 0.014), and both Black (OR 1.24, 95% CI 1.17–1.31, p &lt; 0.001) and Asian (OR 1.14, 95% CI 1.04–1.24, p = 0.004) patients had increased odds of acute renal failure. Respiratory failure was less likely among Black (OR 0.84, 95% CI 0.79–0.90, p &lt; 0.001) and Hispanic (OR 0.76, 95% CI 0.70–0.82, p &lt; 0.001) patients. Encephalopathy was significantly more common in Black (OR 1.29, 95% CI 1.18–1.41, p &lt; 0.001) and Other (OR 1.20, 95% CI 1.01–1.42, p = 0.042) patients. DIC was more frequent in Asian (OR 2.11, 95% CI 1.37–3.27, p = 0.001) and Hispanic (OR 1.53, 95% CI 1.09–2.14, p = 0.014) patients, with a borderline association in Black patients (OR 1.35, p = 0.082). No statistically significant racial differences were noted for CDI or fungal sepsis, although Asian patients trended toward lower odds of CDI (OR 0.64, p = 0.067), and Native American patients had high but non-significant odds for fungal sepsis (OR 3.03, p = 0.287). Conclusion: Our study highlights significant racial disparities in sepsis-related complications among hospitalized MDS patients. Black and Asian patients were more likely to experience acute renal failure and encephalopathy, while Asian and Hispanic patients had higher odds of developing DIC. Conversely, Black and Hispanic patients had lower risk of respiratory failure. These findings underscore the need for race-conscious approaches in sepsis management for patients with MDS and suggest that tailored interventions may be necessary to ensure equitable outcomes across racial groups. Keywords: Myelodysplastic syndromes, sepsis, racial disparities, acute kidney injury, encephalopathy, DIC, respiratory failure, fungal sepsis, National Inpatient Sample