Tan, Jia Yi

Abstract Introduction Chimeric antigen receptor (CAR) T-cell therapies have revolutionized the treatment of relapsed or refractory (R/R) diffuse large B-cell lymphoma (DLBCL), with axicabtagene ciloleucel (axi-cel) and tisagenlecleucel (tisa-cel) both being approved for use. Axi-cel was approved for second-line setting based on studies showing improved outcomes compared to high-dose salvage chemoimmunotherapy followed by autologous hematopoietic stem cell transplantation (HSCT). In contrast, tisa-cel did not demonstrate superiority over traditional salvage therapies in the second-line setting. Although both therapies are currently used in clinical practice, real-world comparative data on the safety of axi-cel versus tisa-cel remain limited. This retrospective study aims to compare the one-year outcomes of axi-cel and tisa-cel in patients with R/R DLBCL, offering practical insights into their outcomes outside of clinical trial settings. Methods A retrospective cohort study was conducted using TriNetX, a global federated health research network that provides access to electronic medical records from approximately 132 million patients, primarily in the United States. Adult patients (≥18 years) diagnosed with R/R DLBCL between January 1, 2022, and January 1, 2024, were identified using ICD-10-CM codes. Patients were categorized into two cohorts: those who received axi-cel and those who received tisa-cel. Propensity score matching (1:1) using nearest neighbor matching with a 0.1 pooled standard deviation caliper was performed for demographics, comorbidities, prior stem cell transplantation, and medications. Study outcomes included 1-year rates of all-cause mortality, all-cause hospitalization, cytokine release syndrome (CRS), immune effector cell-associated neurotoxicity syndrome (ICANS), anemia, neutropenia, thrombocytopenia, heart failure exacerbation, and acute myocardial infarction. Statistical analyses were conducted on the TriNetX platform, with significance set at P<0.05 (two-sided). TriNetX calculates hazard ratios (HRs) and cumulative incidences (CIs) using R survival package version 3.2-3 with the proportional hazard assumption tested using Schoenfeld residuals. This study does not require Institutional Review Board review or informed consent due to the use of de-identified data. Results Our study identified 1,250 patients with R/R DLBCL, including 1,083 patients who received axi-cel and 167 who received tisa-cel. After propensity score matching (PSM), 160 patients were in the axi-cel group (mean age 61.7 ± 11.8 years; 38.8% female; 73.1% White, 8.1% African American) and 160 patients were in the tisa-cel group (mean age 62.3 ± 16.0 years of age; 39.4% female; 75.0% White, 7.5% African American). Axi-cel group had 45% lower risk of all-cause mortality compared to tisa-cel group (HR: 0.55; 95% CI: 0.34–0.87). However, axi-cel group was associated with higher risks of all-cause hospitalization (HR: 1.33; 95% CI: 1.04–1.70), CRS (HR: 2.19; 95% CI: 1.43–3.36), and ICANS (HR: 2.69; 95% CI: 1.42–5.11) compared to tisa-cell group. No significant differences were observed in anemia (HR: 1.18; 95% CI: 0.82–1.72), neutropenia (HR: 1.30; 95% CI: 0.96–1.77), and thrombocytopenia (HR: 0.96; 95% CI: 0.65–1.43) between these two treatment groups. Additionally, there were no significant differences in terms of septic shock (HR: 0.79; 95% CI: 0.42–1.47), pneumonia (HR: 0.64; 95% CI: 0.34–1.21), and heart failure exacerbation (HR: 1.16; 95% CI: 0.76–1.76) between axi-cel group and tisa-cell group. Conclusion This large and multicenter cohort study provides real-world valuable insights into the one-year comparative outcomes of axi-cel and tisa-cel in patients with R/R DLBCL. Our study suggested axi-cel was associated with lower mortality rate, despites its higher rates of all-cause hospitalization, CRS, and ICANS compared to tisa-cell. These findings highlight the importance of close monitoring and supportive care during the first year following CAR-T therapy to optimize patient outcomes. An important limitation of our study is the lack of data on the number of prior lines of therapy, which may have differed between treatment groups and could have influenced clinical outcomes. Future prospective studies with comprehensive clinical data and inclusion of lisocabtagene maraleucel (liso-cel) would be valuable to provide a more complete comparison across currently available CAR T-cell therapies.

Abstract Introduction Chimeric antigen receptor (CAR) T-cell therapy and bispecific antibodies have emerged as transformative options for patients with relapsed or refractory multiple myeloma (MM). Both modalities commonly target B-cell maturation antigen (BCMA) and have demonstrated high overall response rates in pretreated populations ranging from 65-83%. However, the optimal sequencing and comparative effectiveness of these two novel therapies remain unclear. Understanding their treatment outcomes is critical to inform treatment decisions in this rapidly evolving therapeutic landscape. Method A retrospective cohort study was conducted using TriNetX, a global federated health research network that provides access to electronic medical records from approximately 132 million patients, primarily in the United States. Adult patients (≥18 years) diagnosed with relapsed or refractory MM between January 1, 2022, and January 1, 2024, were identified using ICD-10-CM codes. Patients were categorized into two cohorts: those who received CAR T-cell therapy including idecabtagene vicleucel and ciltacabtagene autoleucel and those who received bispecific antibodies including teclistamab and elranatamab. Propensity score matching (1:1) using nearest neighbor matching with a 0.1 pooled standard deviation caliper was performed for demographics, comorbidities, prior stem cell transplantation, medications, and performance status. Study outcomes included 1-year rates of all-cause mortality, all-cause hospitalization, cytokine release syndrome (CRS), immune effector cell-associated neurotoxicity syndrome (ICANS), anemia, neutropenia, thrombocytopenia, sepsis, and pneumonia. Statistical analyses were conducted on the TriNetX platform, with significance set at P<0.05 (two-sided). TriNetX calculates hazard ratios (HRs) and cumulative incidences (CIs) using R survival package version 3.2-3 with the proportional hazard assumption tested using Schoenfeld residuals. This study does not require Institutional Review Board review or informed consent due to the use of de-identified data. Results Our study identified 2,023 patients, including 911 patients who received CAR T-cell therapy and 1,112 who received bispecific antibiotics. After propensity score matching (PSM), each cohort included 649 patients. The CAR T-cell therapy group had a mean age of 66.8 ± 8.4 years, with 41.4% female, 68.0% White, 20.6% African American, and 2.3% Asian. The bispecific antibody group had a mean age of 66.3 ± 9.3 years, with 41.1% female, 67.3% White, 21.1% African American, and 2.2% Asian. CAR T-cell therapy group experienced a 64% lower risk of all-cause mortality (HR 0.36; 95% CI, 0.26–0.48) and a 44% lower risk of all-cause ICU admission (HR 0.56; 95% CI, 0.42–0.75) compared with bispecific antibodies group. However, CAR T-cell therapy group was associated with higher risk of CRS (HR: 1.91; 95% CI: 1.57–2.31), ICANS (HR: 1.50; 95% CI: 1.12–2.01), neutropenia (HR: 2.32; 95% CI: 1.96–2.76), and thrombocytopenia (HR: 1.80; 95% CI: 1.43–2.28) compared to bispecific antibodies group. There was no significant difference observed in anemia (HR: 0.96; 95% CI: 0.82–1.13) between these two treatment groups. Additionally, CAR T-cell therapy group was associated with 46% lower risk of sepsis (HR: 0.54; 95% CI: 0.39–0.75) and 68% lower risk of pneumonia (HR: 0.32; 95% CI: 0.17–0.61) compared to bispecific antibodies group. ConclusionIn this real-world analysis, CAR T-cell therapy demonstrated a substantial lower mortality and reduced ICU utilization compared with bispecific antibodies in patients with relapsed or refractory MM, despite its higher risks of CRS, ICANS, and hematologic toxicities. An important limitation of our study is the lack of data on the number of prior lines of therapy, which likely differed between groups, as bispecific antibodies are typically used in the fourth line or beyond, while CAR T-cell therapies are approved to be used as the second line. This discrepancy may have influenced both mortality and infection rates. Despite the limitation, our findings underscore the need for prospective clinical trials directly comparing CAR T-cell therapy and bispecific antibodies to validate these observations and define the optimal sequencing of these modalities. Furthermore, research into predictive biomarkers and personalized selection algorithms will be crucial to optimize treatment decisions in this rapidly evolving therapeutic landscape.

e19524 Background: Carfilzomib, a second-generation proteasome inhibitor, has emerged as one of the therapeutic agents in the treatment of relapsed or refractory multiple myeloma (MM). Despite its known cardiotoxicity, real-world data on its long-term cardiovascular outcomes remain limited. This study aimed to evaluate the real-world cardiovascular outcomes in patients with relapsed or refractory MM treated with carfilzomib. Methods: We utilized the TriNetX network to identify patients (≥18 years old) with relapsed or refractory MM between January 1, 2014, and January 1, 2019. We further categorized the patients into two groups: patients exposed to carfilzomib and patients not exposed to carfilzomib. Inclusion in the carfilzomib group required exposure to carfilzomib during the 5-year study period. Propensity score matching was performed to match these two groups based on comorbidities, medications, baseline hemoglobin A1c, low-density lipoprotein, and left ventricular ejection fraction to produce two comparable cohorts. The study outcomes were cardiovascular outcomes, including acute heart failure, acute myocardial infarction, cerebrovascular accident, acute venous thromboembolism, all-cause hospitalization, and all-cause mortality over the 5-year follow-up duration. Results: A total of 151,802 patients with relapsed or refractory MM were identified, including 6,386 patients (mean age 64.8 ± 10.6 years) who were exposed to carfilzomib and 145,416 patients (mean age 66.1 ± 12.7 years) who were not. After propensity score matching, there were 4,559 (65.3 ± 10.8 years of age, 44.7% female, 18.2% African American [AA]) patients who were exposed to carfilzomib and 4,559 patients who were not (65.2 ± 12.2 years of age, 45.1% female, 17.0% AA). Exposure to carfilzomib was associated with higher odds of acute heart failure (adjusted odds ratio [aOR]: 1.61; 95% CI: 1.48-1.77, P < 0.001), acute myocardial infarction (aOR: 1.24; 95% CI: 1.03-1.48, P = 0.020), cerebrovascular accident (aOR: 1.97; 95% CI: 1.47-2.64, P < 0.001), acute venous thromboembolism (aOR: 1.79; 95% CI: 1.58-2.03, P < 0.001), all-cause hospitalizations (aOR: 1.91; 95% CI: 1.75-2.09, P < 0.001), and all-cause mortality (aOR: 1.97; 95% CI: 1.80-2.16, P < 0.001). Conclusions: Patients with relapsed or refractory MM who were exposed to carfilzomib had poorer cardiovascular outcomes compared to those who did not.

e19515 Background: The prevalence of diabetes mellitus (DM) is significantly higher in patients with multiple myeloma (MM) compared to the general population. DM has been associated with worse outcomes in MM, including reduced overall survival and increased mortality. The impact of diabetes in patients with MM is further compounded by cardiotoxicity from proteasome inhibitors and the increased thromboembolic risk linked to immunomodulatory agents. Given the potential benefits of sodium-glucose cotransporter-2 (SGLT2) inhibitors, we hypothesized that their use in MM patients with DM could improve clinical outcomes and mitigate adverse events in this population. Methods: We utilized the TriNetX network to identify patients (≥18 years old) with MM and DM between January 1, 2013, and January 1, 2019. We categorized the patients into SGLT2 inhibitors users and SGLT2 inhibitors users. Inclusion in the SGLT2 inhibitors group required exposure to SGLT2 inhibitors for at least 1 year. 1:1 Propensity score matching was performed to match these two groups based on comorbidities, medications, baseline hemoglobin A1c, low-density lipoprotein, and left ventricular ejection fraction to produce two comparable cohorts. The study outcomes include all-cause mortality, all-cause hospitalization, acute venous thromboembolism (VTE), acute heart failure (HF), acute myocardial infarction (MI), cardiac arrhythmia, and cardiac arrest over the 5-year follow-up duration. Results: A total of 43,078 patients were identified, including 3,640 SGLT2 inhibitors users and 39,438 non-SGLT-2 inhibitors users. After 1:1 propensity-score matching, there were 3,379 SGLT-2 inhibitor users (68.9 ± 10.3 years of age, 38.0% female, 23.9% African American [AA]) and 3,379 non-SGLT-2 inhibitor users (68.9 ± 11.0 years of age, 35.9% female, 22.2% AA). SGLT-2 inhibitors users were associated with lower rates of all-cause mortality (odds ratio [OR]: 0.34, 95% confidence interval [CI]: 0.30-0.39) and all-cause hospitalization (OR: 0.52, 95% CI: 0.47-0.58). Lower odds of acute VTE (OR: 0.59, 95% CI: 0.49-0.70), acute HF (OR: 0.89, 95% CI: 0.81-0.98), acute MI (OR: 0.81, 95% CI: 0.69-0.95), cardiac arrhythmia (OR: 0.82, 95% CI: 0.70-0.97), and cardiac arrest (OR: 0.57, 95% CI: 0.44-0.74) were reported among SGLT-2 inhibitors users compared to non-SGLT2 inhibitor users. Conclusions: Our study revealed that only 8.4% of patients with DM and MM were prescribed an SGLT-2 inhibitor. Our study also demonstrated that SGLT2 inhibitor use was associated with lower odds of all-cause mortality and hospitalization, reduced risk of VTE, and favorable cardiovascular outcomes in this patient population.

e19538 Background: Patients with multiple myeloma (MM) and type 2 diabetes mellitus (T2DM) experience increased risks of morbidity and mortality. GLP-1 receptor agonists (GLP-1 RA) offer glycemic and cardiovascular benefits, but their impact on cancer-related outcomes is unclear. This study evaluates the association of GLP-1 RA therapy with clinical outcomes, MM-related biomarkers, and survival in MM patients with T2DM. Methods: We conducted a retrospective cohort analysis using the TriNetX network, including data from 104 healthcare organizations (2014–2019). Two cohorts were defined: (1) MM patients with T2DM starting GLP-1 RA therapy within three months of MM diagnosis and continuing therapy for at least one year (n=1,606 before matching), and (2) MM patients with T2DM not receiving GLP-1 RAs (n=40,306 before matching). Patients included were aged 18 years and older. One-to-one propensity score matching (PSM) balanced systemic MM therapy, BMI, and diabetes medications (e.g., insulin, metformin), yielding 1,279 matched pairs. Outcomes included five-year mortality, ICU and non-ICU hospitalizations, and MM-related biomarkers (hemoglobin, creatinine, neutrophils, and calcium). Most recent lab values were compared in the two groups. Statistical analyses included Kaplan-Meier survival estimates, hazard ratios (HR), risk differences, and T-Test statistics. Results: After PSM, baseline characteristics were well balanced. The mean age was ~ 66 years, white race was ~46%, females were ~ 40%, and hypertension was ~85%. Around 20% of MM patients received autologous transplants and ~27% received lenalidomide in the past. GLP-1 RA therapy was associated with less mortality (HR: 0.44, 95% CI: 0.36–0.54, P < 0.01), ICU admissions (HR: 0.59, 95% CI: 0.50–0.71, P < 0.01), and non-ICU hospitalizations (HR: 0.59, 95% CI: 0.53–0.65, P < 0.01). Patients on GLP-1 RAs had higher hemoglobin levels (11.61 ± 2.30 g/dL vs. 10.75 ± 2.47 g/dL, P < 0.01), with no significant differences in serum creatinine (119.068 µmol/L vs 115.648 µmol/L, P = 0.720) or neutrophils (P = 0.226). Patients who received GLP-1 RAs had higher serum calcium levels (9.17 mg/dL vs. 8.96 mg/dL, P < 0.01). GLP-1 RA use also decreased the incidence of septic shock (HR: 0.53, 95% CI: 0.44–0.64, P < 0.001) and pneumonia (HR: 0.59, 95% CI: 0.49–0.70, P < 0.001). Conclusions: GLP-1 RA therapy improves survival, reduces ICU and non-ICU hospitalizations, and lowers complications in MM patients with T2DM. Biomarker trends over five years suggest potential anticancer effects. Further research should explore whether GLP-1 RAs impact other malignancies, broadening their role in cancer therapy.

ABSTRACTBackgroundChimeric Antigen Receptor (CAR) T‐cell therapy has arisen as a revolutionary treatment for hematologic malignancies. Our study aimed to evaluate how sex differences affect outcomes and complications following CAR T‐cell therapy.MethodsUtilizing the Nationwide Readmissions Database (2018–2020), we identified patients and divided them into male and female groups. Hospital outcomes and complications were compared among these two groups after propensity score matching to match groups based on comorbidities, producing two comparable cohorts.ResultsWe analyzed 2928 patients (1832 males, 62.6%, mean age 60.3 ± 13.7 years; 1096 females, 37.4%, mean age 59.1 ± 13.8 years). After propensity score matching (1:1ratio), 1092 males and females were compared. There were no significant sex differences in early mortality (adjusted odd ratios (aOR): 1.04 [95% CI 0.69–1.57]), 30‐day readmissions (aOR: 1.05 [95% CI 0.86–1.30]), or nonhome discharge (aOR: 0.89 [95% CI 0.60–1.31]). Females had higher odds of leukopenia (aOR: 1.26 [95% CI 1.06–1.50]) but lower odds of acute kidney injury (aOR: 0.68 [95% CI 0.52–0.88]).ConclusionsNo sex differences were found in hospital outcomes, including early mortality, 30‐day readmission, and nonhome discharge after CAR T‐cell therapy.

e15543 Background: In the last two decades, colorectal cancer (CRC) mortality has been decreasing in the United States (US). However, the mortality trends for the different subtypes of CRC, including different sides of colon, rectosigmoid, and rectal cancer remain unclear. Methods: We analyzed death certificate data from CDC WONDER from 1999 to 2020. We calculated age-adjusted mortality rates (AAMR) per 100,000 individuals of CRC and its different subtypes and examined the trends over time by estimating the average annual percent change (AAPC) using the Joinpoint Regression Program. Results: From 1999 to 2020, 1,166,099 deaths were attributed to CRC, of which 957,182 deaths (82.08%) were due to colon cancer, 148,862 deaths (12.77%) from rectal cancer, and 60,055 deaths (5.15%) from rectosigmoid cancer. The overall CRC rates decreased significantly from 26.42 (95% CI, 26.20-26.64) to 15.98 (95% CI, 15.84-16.12) per 100,000 individuals, with AAPC of -2.41 (95% CI, -2.55, -2.27). However, the AAMR of rectosigmoid cancer increased significantly from 0.82 (95% CI, 0.78 -0.86) to 1.08 (95% CI, 1.04-1.11) per 100,000 individuals and the AAMR of right-sided colon cancer increased from 0.57 (95% CI, 0.54-0.60) to 0.70 (95% CI, 0.67-0.73) per 100,000 individuals, with AAPC of +1.10 (95%, 0.21-2.00) and +2.06 (95% CI, 0.85 - 3.27) respectively. Men had higher AAMR of CRC than women (23.90 [95% CI, 23.84-23.96] vs. 17.03 [95% CI, 16.99-17.08] per 100,000 individuals). African Americans had the highest AAMR of CRC (26.93 [95% CI, 26.79-27.07]), followed by Whites (19.60 [95%, 19.56-19.64] per 100,000 individuals), American Indians (14.53 [95%, 14.15-14.92] per 100,000 individuals), and Asians (13.04 [95%, 12.89-13.19] per 100,000 individuals). The overall AAMR of CRC decreased for those aged ≥ 50 years but increased significantly from 1.02 to 1.58 per 100,000 individuals for those aged 15-49 years, with an AAPC of +0.75. The AAMR from CRC was the highest in the Midwest (21.04 [95% CI, 20.96-21.12] per 100,000 individuals), followed by the South (20.51 [95% CI, 20.44-20.57]), the Northeast (20.30 [95% CI, 20.22-20.38] per 100,000 individuals), and the West (18.03 [95% CI, 17.95-18.10] per 100,000 individuals). Rural populations had higher AAMR than urban populations (22.40 [95% CI, 22.30-22.49] vs. 19.60 [95%, 19.56-19.64] per 100,000 individuals). Conclusions: Although overall CRC mortality declined, there were rising trends in young-onset CRC, rectosigmoid cancer, and right-sided colon cancer. Disparities persist in terms of sex, race, geographic region, and urbanization level, emphasizing the need for targeted public health measures.

e23252 Background: The UPMC-Kline Health Center (KHC) in Harrisburg, PA, shows a lower cervical cancer screening rate compared to the general population in the USA (57.08% vs 78%, respectively, based on the Medical Group Fiscal Year 2023 Internal Quality Measures). To understand this gap, we distributed a comprehensive questionnaire to patients, aiming to pinpoint factors contributing to the lower screening rate and plan targeted interventions for improvement. Methods: We randomly distributed questionnaires to female patients aged 21 to 61 during appointment check-in at the KHC, considering our linguistically diverse patient population with surveys available in Spanish, English, and Nepali. Given the diverse linguistic landscape of our patient population, we prepared questionnaires in Spanish, English, and Nepali. The survey aims to identify and address specific clinic-related problems, with a follow-up assessment after a few months to gauge improvements following interventions targeting the underlying causes of screening gaps. Results: Over a three-month span, 65 questionnaires were completed. Among the participants, 38% (25 patients - 7 white/Caucasian, 11 black/African American, 1 Asian, 7 others; 12 Hispanic, 13 non-Hispanic) revealed that they had not undergone screening within the past three years. The analysis of this subgroup unveiled significant issues: 84% (21/25) did not receive paperwork to schedule the test, 88% (22/25) were not contacted to schedule the test, 76% (19/25) did not receive reminder notifications before appointments, and 72%(18/25) expressed concerns about the lack of insurance coverage for costs. Furthermore, 76% (19/25) indicated the requirement to pay a co-pay, and an equal percentage reported difficulties in obtaining the screening test. Additionally, 72%(18/25) mentioned that their healthcare providers did not discuss the screening's importance, while 76%(19/25) noted their providers did not explain the purpose of the test. Conclusions: These findings underscore critical gaps in communication, accessibility, and cost-related barriers to cervical cancer screening at KHC. This ongoing quality improvement project, scheduled for data recollection in a few months, encompasses proposed interventions such as automated reminders, technology integration for communication, and distributing flyers in clinic and waiting areas to foster open communication and address inadequate discussions about the importance of screening. The aim is to improve patient awareness, engagement, and ultimately prevent delayed cancer diagnoses. KHC is committed to enhancing the cervical cancer screening rate to minimize the likelihood of delayed cancer diagnoses.