Liu, Bolun

e20030 Background: Recent studies suggested associations between higher serum Magnesium (Mg) level and better survival outcome in patients receiving immunotherapy, especially in small cell lung cancer (SCLC). However, the prognostic significance of Mg in extensive-stage (ES) SCLC treated with first-line chemoimmunotherapy remains unclear. We evaluated the association between baseline serum Mg and survival outcomes in ES-SCLC receiving platinum–etoposide plus PD-(L)1 blockade. Methods: We conducted a retrospective cohort study of adults with ES-SCLC treated with first-line platinum–etoposide plus atezolizumab or durvalumab at Mayo Clinic via Mayo Clinic Platform in 2018–2025. Baseline average serum Mg level was defined as the mean of all Mg labs from day −30 to day 0 relative to chemoimmunotherapy initiation and categorized as low ( < 1.7 mg/dL), normal (1.7-2.0 mg/dL), or high ( > 2.0 mg/dL) using clinical cutoff. Low and normal groups were combined a priori due to small low-Mg counts. The primary endpoint was overall survival (OS), estimated by KM and compared by log-rank test. OS was measured from chemoimmunotherapy initiation to death and censored at last follow-up. Multivariable Cox proportional hazards models adjusted for age, gender, ECOG, liver/brain metastases status, and smoking status. Results: The cohort included 214 patients, 124 (58%) were female; median age was 68 years; 49% had liver metastases and 30% had brain metastases. Median OS was 10.4 months (95% CI 7.6-15.9) among 99 patients with high serum Mg level, compared with 7.5 months (95% CI 6.7-10.7) in 115 patients with low or normal serum Mg level (Log-rank p = 0.126). High Mg was associated with a trend toward longer OS in unadjusted analyses (Hazard ratio [HR] 0.80, 95% CI 0.59-1.07, p = 0.129); however, the association was not statistically significant after multivariable adjustment (aHR 0.81, 95% CI 0.60-1.10, p = 0.180). Conclusions: Among patients with ES-SCLC treated with first-line platinum–etoposide plus PD-(L)1 blockade, higher baseline serum Mg was associated with numerically longer OS but was not independently associated with survival after multivariable adjustment. These findings suggest baseline serum Mg level may be associated with prognosis and warrant validation in larger cohorts. Baseline characteristics by baseline serum magnesium category in ES-SCLC treated with first-line chemoimmunotherapy. Variable Overall (N=214) High Mg >2.0 (n=99) Low/Normal Mg ≤2.0 (n=115) p value* Age, median (IQR) 68 (62, 74) 68 (61, 74) 69 (62, 75) 0.201 Female, n (%) 124 (58%) 57 (58%) 67 (58%) >0.999 ECOG ≥2, n (%) 58 (27.1%) 28 (28%) 30 (26%) 0.719 Liver metastases, n (%) 105 (49%) 49 (49%) 56 (49%) 0.648 Brain metastases, n (%) 65 (30%) 33 (33%) 32 (28%) 0.469 Ever smoker, n (%) 197 (92.1%) 90 (90.9%) 107 (93.0%) 0.974 *p values: Wilcoxon (age); χ²/Fisher (categorical).

e16510 Background: Early-onset RCC may reflect distinct biology and hereditary predisposition, yet data on stage-specific clinical features and outcomes remain limited. We comprehensively evaluated age-stratified, stage-specific clinical features and survival outcomes using the National Cancer Database. Methods: Adults with histologically confirmed RCC diagnosed between 2004 and 2022 were analyzed. Patients were categorized into three groups by age at diagnosis: early-onset ( < 40 years), middle-aged (40–50 years), and late-onset ( > = 50 years). The sociodemographic and clinical characteristics, comorbidities, histology, and treatment patterns were compared using descriptive statistics. Overall survival (OS) was evaluated using Cox proportional hazards models, adjusting for the aforementioned variables. Stage-specific analyses were conducted, including a metastatic disease cohort. Results: Among 742,114 patients, 4.3% were classified as early-onset, 10.9% as middle-aged, and 84.8% as late-onset. Overall, 12.6% presented with metastatic disease. Compared with late-onset, early-onset patients were more likely to be from racial minority populations (non-White: 16.9 % vs. 20.2 % in late-onset), uninsured, and had fewer comorbidities (Charlson–Deyo score 0: 85.2% vs. 65.2%). Early-onset RCC was characterized by a lower proportion of papillary RCC (8.9% vs. 12.5%) and higher proportions of clear cell (54.9% vs. 50.8%) and chromophobe RCC (9.3% vs. 4.5%) than late-onset RCC and more likely to undergo partial nephrectomy (50.4% vs. 30.2%). They also presented with earlier-stage disease, with lower rates of stage III (7.4% vs. 10.2% vs. 13.4%) and stage IV disease (5.4% vs. 8.9% vs. 13.5%) compared with middle-aged and late-onset groups. Among patients with metastatic disease, early-onset RCC demonstrated higher minority representation (30.8% vs. 14.1%) and a higher prevalence of non-clear cell histology (70.6% vs. 58.1%). In multivariable analysis, compared with early-onset RCC, middle-aged (HR 1.44, 95% CI 1.39–1.50; P < 0.001) and late-onset patients (HR 2.83, 95% CI 2.74–2.93; P < 0.001) experienced significantly worse OS. However, among metastatic disease, this survival advantage was attenuated. Early-onset patients had similar OS to middle-aged patients (HR 0.99, 95% CI 0.93–1.05, p = 0.69) and late-onset patients only had a modestly worse OS than the early-onset group (HR 1.09, 95% CI 1.03–1.15 p = 0.003). Conclusions: Early-onset RCC was associated with more favorable baseline characteristics, earlier stage at diagnosis, and higher utilization of nephron-sparing nephrectomy, corresponding to improved OS. However, this survival advantage diminishes in metastatic disease despite better baseline health, highlighting stage-dependent differences in outcomes and suggesting distinct histologic patterns in advanced early-onset RCC.

1564 Background: Adolescent and young adult (AYA) females with early-stage ER-negative and/or HER2-positive breast cancer commonly receive chemotherapy to reduce risk of recurrence. Fertility concerns, counseling, and preservation may influence chemotherapy decisions and time to chemotherapy (TTC) initiation. Methods: We surveyed AYA survivors of stage I–III premenopausal ER-negative and/or HER2-positive breast cancer treated at Kaiser Permanente Northern and Southern California (2013-2022). Fertility concerns were defined as not having completed desired family size or being unsure about having completed desired family size at diagnosis. We summarized receipt of fertility counseling, receipt of chemotherapy, and use of oocyte/embryo cryopreservation for fertility preservation (FP). Among fertility-concerned patients who received chemotherapy, TTC (days from diagnosis) was assessed separately for neoadjuvant chemotherapy (NAC) vs for adjuvant chemotherapy (AdjC). Time to NAC was natural log–transformed and modeled with multivariable log-linear regression to estimate relative differences in TTC, adjusting for stage, study site, ER, HER2, age, and diagnosis year. Results: Of 363 respondents, 197 (54%) had fertility concerns at diagnosis; 183/197 (93%) received chemotherapy, similar to 153/166 (92%) among those without concerns (p=0.7). Of the concerned chemotherapy recipients, 45 (25%) saw a fertility specialist but did not pursue FP while 55 (30%) underwent FP. For the 112 fertility-concerned NAC recipients, FP was associated with longer TTC than no fertility specialist counseling (mean=41 vs. 30 days; adjusted ratio=1.39; 95% CI 1.15–1.69), whereas fertility specialist counseling without FP was not (mean= 31 vs. 30 days, adjusted ratio=1.04; 95% CI 0.86–1.25). For the 71 fertility-concerned AdjC recipients, TTC was similar for patients who did not see a fertility specialist (mean=63 days), those who froze oocytes/embryos (mean=65 days), and those who saw a fertility specialist but did not pursue FP (mean=69 days). Conclusions: In this AYA breast cancer cohort, there was no evidence that fertility concerns led patients to decline chemotherapy. FP was associated with a modest delay in NAC initiation (<2 weeks on average). Time to chemotherapy (TTC) among 183 AYA patients with ER− and/or HER2+ breast cancer and fertility concerns. Fertility-focused care N (n=183) Neoadjuvant chemotherapy (n=112) Mean TTC, days Relative difference in TTC, adjusted ratio (95%CI) Adjuvant chemotherapy (n=71) Mean TTC, days No fertility counseling from a specialist 83 (45%) 55 (49%) 29.6 Reference 28 (39%) 62.6 Received fertility counseling from a specialist No fertility preservation 45 (25%) 28 (25%) 30.7 1.04 (0.86,1.25) 17 (24%) 68.6 Fertility preservation 55 (30%) 29 (26%) 41.2 1.39 (1.15,1.69) 26 (37%) 64.6

Abstract Immune checkpoint inhibitor–associated immune thrombocytopenia (ICI-ITP) has been described in case reports and small case series, but comprehensive data on its incidence, risk factors, clinical features, treatment, and outcomes are lacking. We reviewed medical records of all adults initiating ICI therapy between 2016 and 2023 at 29 US hospitals across 7 major cancer centers to identify patients with ICI-ITP. Multivariable logistic regression was used to identify risk factors, and Cox modeling was performed to assess the association between ICI-ITP, its severity, and mortality. Among 86 467 patients, ICI-ITP occurred in 214 (0.25%). Independent risk factors included lower baseline platelet count, combination ICI therapy, stage IV cancer, and additional immune-related adverse events. ICI-ITP occurred at a median of 8 weeks (interquartile range [IQR], 4-18) after ICI initiation, with a median nadir platelet count of 41 × 109/L (IQR, 17 × 109/L to 64 × 109/L). Patients were treated with glucocorticoids (n = 106 [49.5%]), immune globulin (n = 39 [18.2%]), and thrombopoietin receptor agonists (n = 29 [13.6%]). Recovery occurred in 161 patients (75.2%) at a median of 2.3 weeks (IQR, 1.0-5.3). Of 76 patients rechallenged with ICIs, 23 (30.3%) developed recurrent ICI-ITP. ICI-ITP and its severity were associated with higher all-cause mortality, with a nearly threefold increase in risk among patients with severe ICI-ITP than those without ICI-ITP (adjusted hazard ratio, 2.96 [95% confidence interval, 2.14-4.08]). These findings establish ICI-ITP as a rare but clinically significant complication of ICI therapy, provide, to our knowledge, the first large-scale description of its risk factors and clinical course, and underscore the importance of timely recognition and management.

Abstract INTRODUCTION Immune checkpoint inhibitors (ICIs) have emerged as a cornerstone of cancer therapy. However, despite their efficacy, ICIs can cause a unique spectrum of autoimmune toxicities known as immune-related adverse events (irAEs). In contrast to irAEs involving other organ systems, hematologic irAEs such as ICI-associated immune thrombocytopenia (ICI-ITP) are less common. As a result, existing data on ICI-ITP are largely confined to isolated case reports, single-center case series, and pharmacovigilance databases lacking granular clinical data. To address this key knowledge gap, we sought to comprehensively characterize the incidence, risk factors, clinical features, treatments, and outcomes associated with ICI-ITP. METHODS We performed a multicenter cohort study of adult patients who initiated ICI therapy at 29 hospitals across 7 major cancer centers in 11 geographically diverse states in the US between 2016-2023. ICI-ITP was defined as a decline in platelet count to &lt;100 x109/L in the absence of an alternative more plausible etiology of thrombocytopenia. Patients with hematologic malignancies were excluded, as were those who received cytotoxic chemotherapy within 30 days prior to thrombocytopenia onset. For each patient identified as having ICI-ITP, we collected data on demographics, comorbidities, medications, laboratory values, treatments, and outcomes. All data were extracted by manual chart review. To identify risk factors for ICI-ITP and to examine its association with death, for each case of ICI-ITP we also collected data on two control patients who initiated ICI therapy at the same site and in the same year but without development of ICI-ITP. We used multivariable logistic regression to identify independent risk factors for ICI-ITP and its recovery (the latter defined according to criteria established by the ITP International Working Group). We used a multivariable Cox model to examine the association between ICI-ITP and its severity with all-cause mortality. RESULTS We identified a total of 214 patients who developed ICI-ITP among 86,648 examined (0.25%). The incidence was highly consistent across sites (range, 0.15–0.30%). Risk factors for ICI-ITP included simultaneous receipt of two different classes of ICIs, additional irAEs, and a lower baseline platelet count. ICI-ITP developed at a median of 8 weeks (IQR, 4–18) following ICI initiation. The median nadir platelet count was 41 x109/L (IQR, 17–64). Six out of 214 patients (2.8%) developed a major bleed, and 16 patients (7.5%) developed a clinically relevant non-major bleed. Cell-bound anti-platelet antibody testing was positive in 6 of 8 patients (75.0%) for whom it was assessed, and median circulating thrombopoietin levels (201 pg/mL [IQR, 178–295]) were similar to those seen in primary ITP. Treatments used included glucocorticoids (49.5%), immune globulin (18.2%), and thrombopoietin receptor agonists (13.6%). Overall, 161 patients (75.2%) recovered from ICI-ITP at a median of 2 weeks (IQR, 1–5) following ICI-ITP onset. Predictors of recovery included additional irAEs and a higher nadir platelet count. Treatment response was observed in 57.0%, 56.4%, and 58.3% of patients within 60 days following initiation of glucocorticoids, immune globulin, and thrombopoietin receptor agonists, respectively. Of 76 patients rechallenged with an ICI, 23 (30.3%) developed recurrent ICI-ITP at a median of 9 weeks (IQR, 2–15); 17 of these 23 patients (73.9%) recovered. Finally, ICI-ITP and its severity were monotonically associated with a higher risk of death (adjusted hazard ratio 2.96 [95% CI, 2.14–4.08] for those with severe ICI-ITP compared to those without ICI-ITP). CONCLUSION In this multicenter study involving patients treated with ICIs at 29 hospitals across the US, we identified 214 patients with ICI-ITP. For the first time, we characterize in detail the incidence, risk factors, clinical features, treatments, and outcomes of ICI-ITP, a relatively novel disease entity. We found that more than half of patients responded to conventional ITP-directed therapies, and that most patients rechallenged did not develop recurrent ICI-ITP. We also found that ICI-ITP was independently associated with an increased risk of death, including a nearly 3-fold increased risk in those with severe ICI-ITP. These findings highlight ICI-ITP as a rare but clinically significant complication of ICI therapy that hematologists must be equipped to recognize and manage.

572 Background: Neoadjuvant endocrine therapy (NET) is sometimes used to shrink hormone receptor-positive (HR+) breast cancers to improve breast conservation rates and reduce axillary nodal burden. At the beginning of the COVID-19 pandemic, several organizations endorsed NET use to mitigate the harm of surgery delay when cancer operations were less available due to infection transmission concerns. However, the real-world patterns of NET during this period are understudied. This study investigated the alteration of NET utilization patterns during the COVID-19 pandemic in the United States using the National Cancer Database (NCDB). Methods: We identified patients diagnosed with stage I-III invasive HR+/human epidermal growth factor receptor 2-negative (HER2-) breast cancer between 2018-2022 in the NCDB. Estrogen receptor and/or progesterone receptor positivity was required for inclusion in the cohort. Receipt of NET was defined as initiation of endocrine therapy ≥ 14 days before the patient’s first surgical procedure. The study cohort generation and statistical analysis were conducted using Stata and R 4.4.3. A two-tailed p value < 0.05 was considered statistically significant. Results: 495,098 patients were included in the cohort, 195,371 in 2018-2019 (pre-pandemic), 91,686 in 2020 (early pandemic), 106,157 in 2021 (mid-pandemic), and 101,884 in 2022 (late pandemic). NET utilization was increased in the early pandemic compared to the pre-pandemic (seen in 5.8% vs 2.4% of the cohort, Chi-square p value < 0.001), but this use fell back to 3.4% in the mid-pandemic and 3.5% in the late-pandemic. The median (IQR) duration of NET was 15.7 (6.4-26.6) weeks in the pre-pandemic, 9.3 (5.4-18.7) weeks in the early pandemic, 13.2 (5.8-25.7) weeks in the mid-pandemic, and 12.0 (6-24.6) weeks in late pandemic (Kruskal-Wallis p value = 0.001). The transient increase in NET utilization during the early pandemic was more pronounced among patients with tumors < 5 cm and node-negative disease. Conclusions: Our study identified a significant shift in the utilization of NET for HR+/HER2- breast cancer during the COVID-19 pandemic. Pandemic-era NET policies produced a short-lived practice change that was only partially sustained once surgical access normalized. NET utilization (%) by subgroup and year for stage I-III HR+/HER2- breast cancer. Variable Category 2018-2019 2020 2021 2022 Overall NET Use 2.4 5.8 3.4 3.5 Age Group (years old) <50 2.2 4.9 3.9 4.0 >=50 2.4 6.0 3.3 3.4 Tumor Size <5 cm 2.0 5.5 2.9 3.1 >=5 cm 9.0 9.7 11.2 11.6 Histology Subtype Ductal 2.2 5.5 3.3 3.4 Lobular 3.6 7.1 4.4 4.8 Ductal/Lobular 2.6 6.2 4.3 3.6 Other 1.9 6.7 2.5 2.6 KI67 <20% 2.5 6.4 3.4 3.3 >=20% 2.3 5.5 3.5 3.7 Tumor Grade Well differentiated 1.9 5.8 2.4 2.6 Moderately differentiated 2.7 6.1 3.9 3.9 Poorly differentiated/undifferentiated 2.9 4.8 4.3 4.8 Node Positivity Positive 5.2 5.6 9.3 9.5 Negative 2.0 5.8 2.6 2.7

Acute myeloid leukemia (AML) is an aggressive hematologic malignancy characterized by the clonal proliferation of myeloid precursors and rapid progression. Historically consisting of intensive chemotherapy, AML management has evolved significantly due to advances in molecular diagnostics and risk stratification. This review discusses current therapeutic paradigms in AML, emphasizing the growing role of personalized medicine across age and risk groups. For younger, fit patients, intensive regimens such as the “7 + 3” protocol remain the standard, often enhanced by targeted agents like FMS-like tyrosine kinase 3 (FLT3) and IDH inhibitors. Older or unfit individuals benefit from low-intensity treatments such as hypomethylating agents combined with venetoclax, now considered a frontline standard of care. The use of liposomal chemotherapy (CPX-351), measurable residual disease (MRD) monitoring, and maintenance therapy further refine post-remission strategies. Emerging therapies, including menin inhibitors, antibody–drug conjugates, and immunotherapies like CAR-T cells and vaccines, offer additional options, especially in relapsed/refractory settings. This comprehensive review outlines the current landscape and future directions in AML therapy, emphasizing the transition toward individualized, mutation-driven treatment strategies.

Background/Objectives: Patients with Non-Alcoholic Fatty Liver Disease (NAFLD) are reported to have an increased risk of developing severe infections, leading to hospitalizations with sepsis. However, data regarding the impact of comorbid NAFLD on in-hospital outcomes of patients with sepsis is scarce. Methods: This nationwide retrospective observational study using discharge data from the National Inpatient Sample (NIS), Healthcare Cost and Utilization Project (HCUP), and Agency for Healthcare Research and Quality included 21,057,911 adult patients who were admitted to hospitals in the United States between 2000 and 2019 with a primary discharge diagnosis of sepsis. These patients were categorized according to the presence or absence of comorbid NAFLD. The twenty-year trend of nationwide NAFLD prevalence among sepsis inpatients was elucidated. Multivariable logistic regression analysis was used to analyze NAFLD’s impact on sepsis outcomes. Results: In the twenty-year study period, the prevalence of NALFD among sepsis inpatients trended up from 1.2% in 2000 to 4.2% in 2019. Similar trends were observed in regional analysis. While overall sepsis mortality decreased, comorbid NAFLD in sepsis patients was consistently associated with a higher adjusted in-hospital all-cause mortality rate (adjusted odds ratio (OR), 1.19; 95% confidence interval (CI), 1.07–1.32), higher odds of developing septic shock, and higher likelihood of development of multi–organ dysfunction. Conclusions: Comorbid NAFLD in the stage of NASH or cirrhosis is associated with higher in-hospital all-cause mortality and worse clinical outcomes in sepsis inpatients. Addressing this rising epidemic will be of paramount importance to improve sepsis in-hospital outcomes.

Blood transfusion is a common therapeutic intervention in hospitalized patients. There are numerous indications for transfusion, including anemia and coagulopathy with deficiency of single or multiple coagulation components such as platelets or coagulation factors. Nevertheless, the practice of transfusion in critically ill patients has been controversial mainly due to a lack of evidence and the need to consider the appropriate clinical context for transfusion. Further, transfusion carries many risk factors that must be balanced with benefits. Therefore, transfusion practice in ICU patients has constantly evolved, and we endeavor to present a contemporary review of transfusion practices in this population guided by clinical trials and expert guidelines.

Abstract Background It was reported that patients with Non-Alcoholic Fatty Liver Disease (NAFLD) were at increased risk of contracting severe infections requiring hospitalization which could end up with sepsis. However, data regarding the impact of comorbid NAFLD on the in-hospital outcomes of sepsis admission is scarce. Methods This nationwide retrospective observational study included 21,057,911 adult patients who were admitted into hospitals in the United States between 2000 and 2019 with a primary discharge diagnosis of sepsis. These patients were categorized according to the presence or absence of comorbid NAFLD. The twenty-year trend of nationwide NAFLD prevalence among sepsis inpatients was elucidated. Multivariate logistic regression analysis was used to analyze NAFLD's impact on in-hospital outcomes of sepsis. Results In the twenty-year study period, the prevalence of NALFD among sepsis inpatients trended up from 1.2% in 2000 to 4.2 % in 2019. While sepsis mortality had trended down, comorbid NAFLD in sepsis patients was consistently associated with a higher adjusted in-hospital all-cause mortality rate (adjusted odds ratio (OR), 1.45; 95% confidence interval (CI), 1.42-1.48), higher odds of developing septic shock, and multi-organ dysfunctions (including cardiovascular-, renal-, and hepatic dysfunction). They were more likely to be discharged to another acute hospital. The length of stay of sepsis patients with NAFLD who died in the hospital was significantly shorter than those without NAFLD. Conclusions Comorbid NAFLD is associated with higher in-hospital all-cause mortality and worse clinical outcomes in sepsis inpatients. Addressing this rising epidemic will be of paramount importance to improve sepsis in-hospital outcomes.