Introduction Older adults represent the majority of patients with acute myeloid leukemia (AML), and an increasing proportion receive allogeneic hematopoietic cell transplantation (alloHCT). Mutations in the FMS-like tyrosine kinase 3 gene (FLT3) confer high relapse risk, and post-transplant maintenance with FLT3 tyrosine kinase inhibitors (FLT3-TKIs) is guideline-recommended. However, real-world utilization, adherence, and tolerability of FLT3-TKIs in older adults remain poorly characterized. Materials and methods Using 100% Medicare claims (Parts A/B/D and Medicare Advantage encounter data), we conducted a retrospective cohort study of beneficiaries ≥65 years old with AML who received alloHCT between January 1, 2016 and June 30, 2024, and initiated FLT3-TKI maintenance (gilteritinib, midostaurin, or sorafenib) within 100 days post-transplant. Baseline demographics, comorbidities, prior therapy, and health care resource utilization (HCRU) were captured from 2010 through the index date. Adherence was assessed using proportion of days covered (PDC). Dose modification, FLT3-TKI switching, and post-transplant HCRU were evaluated descriptively. Centers for Medicare & Medicaid Services suppression rules were applied throughout. Results Of 7403 eligible older adults with AML undergoing alloHCT, 150 (2.0%) initiated FLT3-TKI maintenance (gilteritinib: 54.7%, midostaurin: 24.0%, sorafenib: 21.3%). Mean age was 70.5 years, and 59.3% had Charlson Comorbidity Index ≥4. Utilization of post-transplant FLT3-TKIs was sustained from 2020 onwards at approximately 20% of eligible patients annually. Overall adherence was modest, with a mean PDC of 47% and very few patients achieving PDC ≥80%. Higher mean PDC was observed in patients ≥70 years of age, those with fewer comorbidities, those previously treated with low-intensity chemotherapy, and those who received gilteritinib as maintenance. Among patients treated with gilteritinib, two-thirds had no evidence of dose change, and no patients switched to an alternative FLT3-TKI. Across all patients, post-alloHCT HCRU was predominantly outpatient visits, with low hospitalization rates across FLT3-TKIs. Discussion In this first real-world analysis of post-alloHCT FLT3-TKI maintenance in older adults, utilization was low and adherence was modest, although not impaired by age alone. Gilteritinib demonstrated the highest adherence and appeared to have favorable tolerability. Strategies to improve adherence and prospective data in older adults are needed to maximize the benefits of FLT3-TKI maintenance in this population.

Chemotherapy-naïve patients with metastatic castration-resistant prostate cancer (mCRPC) treated with abiraterone (ABI) have a higher cardiovascular (CV) event-related hospitalization risk than those treated with enzalutamide (ENZA). This study aimed to assess CV event risk in chemotherapy-naïve patients with mCRPC treated with ENZA or ABI and to provide outcome data based on CV disease (CVD) history using the US Medicare database. Chemotherapy-naïve patients with mCRPC (≥ 65 years) who initiated ENZA or ABI (September 2014 − May 2017) were included. The primary endpoint was a 4-point major adverse CV event (MACE; a composite of acute myocardial infarction, stroke, unstable angina/revascularization, and heart failure). Atrial fibrillation, venous thromboembolism, and all-cause death were also analyzed. Further, the risk of adverse CV outcomes was compared between ENZA- and ABI-treated cohorts (overall population and by CVD-risk subgroup). Sensitivity analysis was performed using a 5-point MACE (4-point MACE plus CV-related death) as the endpoint. Of 6319 patients (ENZA: 2934; ABI: 3385), 2913 propensity score-matched patients were included from each group (prior CVD: 76

In FLT3-mutated (FLT3mut+) acute myeloid leukemia (AML), relapse after allogeneic hematopoietic cell transplantation (alloHCT) is the leading cause of treatment failure and mortality. We evaluated real-world adherence and persistence of FLT3-like-tyrosine kinase inhibitors as alloHCT maintenance in FLT3mut+ AML. Claims data were extracted from adults with AML with ≥1 alloHCT between January 2016 and June 2022 who received gilteritinib, midostaurin, or sorafenib as post-alloHCT maintenance. Adherence (PDC; days covered ≥80% during follow-up) and persistence (days receiving treatment without switch/gap >60 days) were assessed. Of 162 patients, 41, 53, and 68 received post-alloHCT gilteritinib, midostaurin, or sorafenib, respectively. Adherence was higher in patients with a history of relapsed/refractory disease before alloHCT (n = 106 [65.4%], p = .021). Although this study did not focus on outcomes, no significant differences in post-alloHCT relapse by PDC were found. Discontinuation risk was higher for midostaurin (HR = 2.79, p = .0005) and sorafenib (HR = 1.74, p = .046) versus gilteritinib in patients with Commercial insurance vs Medicare/Medicaid (HR = 1.68, p = .019).

OBJECTIVE:To describe real-world patient characteristics, prior treatment patterns, and associated healthcare resource utilization (HRU) and costs among patients with locally advanced/metastatic urothelial carcinoma (la/mUC) treated with enfortumab vedotin (EV). METHODS:This retrospective study used the United States (US) Centers for Medicare and Medicaid Services 100% Medicare claims data from 2015 to 2020. Included patients had a diagnosis of la/mUC and received treatment with EV. The index date was the EV initiation date. Endpoints included HRU and costs 12 months before the index date (baseline period) and treatment patterns before EV initiation. Results were summarized descriptively using means and standard deviations for continuous variables, and frequency counts and percentages for categorical variables. RESULTS:Among the 529 included patients, the mean age at the time of EV initiation was 76.5 years. Most patients were White (88.1%) and male (77.1%). Common comorbidities were hypertension (85.1%), renal disease (65.2%), and peripheral vascular disease (42.5%). Platinum-based chemotherapy was the most frequent therapy two lines before EV initiation (43.9%). The most frequent therapy in the line before EV initiation was PD-1/L1 inhibitors (61.4%). The median duration of EV therapy was 4.1 months. The mean all-cause healthcare cost during the baseline period was $106 258 per patient, and 86% had at least one outpatient visit. CONCLUSIONS:This real-world study demonstrated that most US patients with la/mUC received platinum-based chemotherapy or a PD-1/L1 inhibitor prior to EV therapy from 2015 to 2020. HRU and costs 12 months before EV initiation suggest a substantial burden in this population. Long-term studies with more recent data are warranted.

698 Background: Due to the evolving treatment landscape for muscle-invasive bladder cancer (MIBC), a better understanding of current treatment patterns among real-world patients is needed. This study reported demographic and clinical characteristics and examined the real-world treatment patterns of patients with MIBC in the US. Methods: This non-interventional, retrospective cohort study extracted data from the Inovalon Insights Payer-Sourced dataset, a claims database, from January 1, 2020–December 31, 2021. Patients aged ≥18 years with MIBC who were treated with cystectomy with or without neoadjuvant systemic treatment were followed from index date (first day of cystectomy or neoadjuvant systemic treatment) until the end of the study, loss of follow-up, diagnosis of metastasis, or end of enrollment in their medical or pharmacy health plan, whichever occurred first. Patients with metastasis from tumor types such as solid tumors, leukemia, lymphoma and, myeloma, with secondary malignancies, or participating in clinical trials by the index date were excluded. Results were reported for patients who received neoadjuvant and/or adjuvant treatment by therapy type. Results: Among 332 eligible patients, the mean (standard deviation [SD]) age was 64.3 (10.2) years, and 245 (73.8%) patients were male. Prior transurethral resection of a bladder tumor was reported for 236 (71.1%) patients. Common comorbidities were hypertension (198 [59.6%]), urinary tract infection (94 [28.3%]), diabetes without chronic complications (88 [26.5%]), and chronic pulmonary disease (80 [24.1%]). The mean (SD) age-adjusted Charlson Comorbidity Index was 6.3 (2.3). A total of 137 (41.3%) patients underwent cystectomy alone, while 195 (58.7%) patients received neoadjuvant systemic therapy followed by cystectomy. A total of 27 (8.1%) patients received both neoadjuvant and adjuvant therapies. In the 195 patients receiving neoadjuvant systemic therapies, 153 (78.5%) received chemotherapy with cisplatin; most commonly cisplatin + gemcitabine (76 [39.0%]) followed by cisplatin + doxorubicin + methotrexate + vinblastine (56 [28.7%]). Chemotherapy without cisplatin (41 [21.0%]) and immunotherapy (1 [0.5%]) were also given as neoadjuvant systemic therapies. Adjuvant therapies were received by 39 (11.7%) patients; of which, 20 (51.3%) received immunotherapy, 15 (38.5%) received chemotherapy with cisplatin, and 4 (10.3%) received chemotherapy without cisplatin. Cisplatin + gemcitabine (10 [25.6%]) and nivolumab monotherapy (10 [25.6%]) were the most common adjuvant treatments. Conclusions: Patients with MIBC had a substantial comorbidity burden. Many patients did not receive neoadjuvant or adjuvant treatment, indicating a persistent unmet need in this patient population for alternative therapeutic regimens. Further evaluation of treatment patterns is needed as the landscape evolves.

5041 Background: Prior studies suggest that chemotherapy-naïve pts with mCRPC treated with AA have a higher CV event-related hospitalization risk than those treated with ENZA. To further explore this association, this real-world, comparative causal inference study used a large US dataset to assess CV event risk in chemotherapy-naïve pts with mCRPC who initiated treatment (Tx) with ENZA or AA and provide outcome data based on history of (h/o) CV disease (CVD). Methods: Using US Medicare fee-for-service claims (Jan 2010–Dec 2022), we identified chemotherapy-naïve pts aged ≥65 years with mCRPC who initiated ENZA or AA between Sep 2014 and May 2017. The primary endpoint was a 4-point major adverse CV event (MACE-4; composite of acute myocardial infarction [AMI], stroke, unstable angina/revascularization [UA/R], and heart failure). Atrial fibrillation (AFib), venous thromboembolism (VTE), and all-cause death were also analyzed. Groups were propensity score matched (PSM) to adjust for differences in pt characteristics, assessed using standardized mean difference (SMD). Cause-specific Cox proportional hazards models were used to comparethe risk of CV outcomes between intention-to-treat cohorts, with death as a competing event. Subgroup analyses were conducted based on h/o CVD. Sensitivity analysis was performed with a MACE-5 endpoint, defined as MACE-4 or CV-related death. Results: Of 6319 pts in the total study population (ENZA: 2934; AA: 3385), 2913 PSM pts were included from each group. The ENZA and AA cohorts had similar baseline characteristics even before PSM (SMD<0.1), with a mean (standard deviation) age of 78.8 (7.3) years; 76% of pts had prior CVD. Compared with pts on ENZA, pts on AA had a significantly higher risk of experiencing MACE-4—particularly UA/R—as well as a higher risk of AFib and VTE (Table). Similar results were found in the subgroup of pts with a h/o CVD and the sensitivity analyses. Additionally, pts on AA had a higher risk of all-cause death than pts on ENZA, regardless of CVD history (h/o CVD hazard ratio [HR]: 1.14, 95% confidence interval [CI]: 1.07–1.21, P =0.0001; no h/o CVD HR: 1.12, 95% CI: 1.01–1.26, P =0.036). Conclusions: This matched analysis of US Medicare beneficiaries showed an increased risk for MACE-4, AFib, and VTE in pts with mCRPC treated with AA compared to ENZA, in the overall pt population and pts with a h/o CVD. The risk of all-cause death was higher with AA in all pts. These findings provide insights into Tx decision-making for pts with mCRPC, especially those at high risk of CV events. Outcomes HR* (95% CI) P -value MACE-4 1.12 (1.02–1.24) 0.028 AMI 1.01 (0.76–1.32) 0.987 Stroke 0.92 (0.70–1.20) 0.505 UA/R 1.13 (1.01–1.26) 0.041 Heart failure 1.19 (0.90–1.58) 0.237 AFib 1.73 (1.31–2.29) 0.0001 VTE 1.37 (1.02–1.85) 0.037 All-cause death 1.13 (1.07–1.19) 0.0001 *ENZA = reference group.

Background Given the changing treatment landscape for locally advanced or metastatic urothelial carcinoma (la/mUC), this study aimed to describe real-world treatments, overall survival (OS), health care resource utilization (HCRU), and costs among US patients with la/mUC receiving first-line therapy. Methods This retrospective study was conducted using 100% Medicare claims data (2015-2020). Patients with la/mUC were selected; initiation of first-line therapy was the index date. Treatments and OS were assessed during follow-up (index date to the earliest of end of data availability, health plan coverage, or death). All-cause HCRU and costs (2021 USD) were assessed during the first-line treatment period (index date to the earliest of first-line discontinuation, switch to second-line therapy, end of follow-up, or death). Outpatient pharmacy costs were not included. All-cause OS from start of first-line therapy was estimated using the Kaplan-Meier approach. The HCRU, cost, and OS analyses were stratified by 3 index treatment groups-platinum-based chemotherapy, non-platinum-based chemotherapy, and programmed cell death protein 1/ligand 1 (PD-1/L1) inhibitor monotherapy-and adjusted for baseline characteristics. Results Of 9,939 patients included, 77.1% were men and mean age was 76 years. In total, 5,050 (50.8%) received platinum-based chemotherapy, 1,361 (13.7%) received non-platinum-based chemotherapy, and 3,242 (32.6%) received PD-1/L1 inhibitor monotherapy for first-line la/mUC. Median OS was 12.9, 12.9 (P = 0.960), and 9.0 months (P < 0.001) with platinum-based chemotherapy (reference), non-platinum-based chemotherapy, and PD-1/L1 inhibitor monotherapy, respectively. Most (> 99%) patients had >= 1 outpatient visit during the treatment period; mean number of visits per patient was 13.1 with platinum-based chemotherapy, 10.5 with non-platinum-based chemotherapy, and 18.3 with PD-1/L1 inhibitor monotherapy. In general, HCRU was significantly lower for patients receiving PD-1/L1 inhibitor monotherapy versus platinum-based chemotherapy. However, costs were significantly higher with PD-1/L1 inhibitor monotherapy versus platinum-based chemotherapy. Mean total monthly cost per patient was $10,285 for platinum-based chemotherapy, $8,982 for non-platinum-based chemotherapy, and $18,147 for PD-1/L1 inhibitor monotherapy. Conclusions From 2015 to 2020, patients with la/mUC had substantial HCRU and costs and short survival, regardless of first-line treatment. More effective therapies were needed to prolong survival and reduce the economic burden of la/mUC. (c) 2024 The Authors. Published by Elsevier Inc. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/)

Background : Older patients with relapsed acute myeloid leukemia (AML) often require transfusion support due to persistent cytopenias from both disease progression and targeted therapy. Gilteritinib is an approved treatment for adults with relapsed or refractory AML with FLT3 mutations, yet real-world data on transfusion burden during its use remains limited. This study characterizes transfusion burden among Medicare beneficiaries with relapsed AML receiving gilteritinib. Understanding transfusion burden is critical, as high transfusion dependence has been associated with increased healthcare utilization, reduced quality of life, and poorer clinical outcomes in this population. Methods : This retrospective observational cohort study analyzed Medicare beneficiaries aged ≥65 years with relapsed AML using claims data from the Centers for Medicare & Medicaid Services, including both Medicare Fee-for-Service (Parts A, B, and D) and Medicare Advantage (Part C) enrollees. The study period was from July 1, 2016, to December 31, 2024 (Part C: January 1, 2017, to December 31, 2022). Eligible patients had a confirmed AML diagnosis, evidence of relapse, and a prescription for gilteritinib following relapse. Patients were required to have ≥180 days of continuous enrollment prior to diagnosis and no prior history of acute promyelocytic leukemia, acute lymphocytic leukemia, chronic lymphocytic leukemia, chronic myeloid leukemia or allogeneic hematopoietic cell transplantation. Transfusion independence was defined as a continuous 56-day period without any red blood cell or platelet transfusions, assessed on a rolling basis. Results : Among 169,642 Medicare beneficiaries diagnosed with AML, 962 met the study's eligibility criteria, of whom 799 initiated gilteritinib for relapsed disease. The median follow-up duration was 136 days [Interquartile range (IQR)=71-320] and the median age at diagnosis was 74 years (IQR=70-78) in all patients. The majority of patients were male (52.9%, n=423) and White (84.7%, n=677). Patients had a mean Charlson Comorbidity Index score of 2.9 (SD=1.46), including common comorbidities: 28.9% (n=231) with congestive heart failure, 27.7% (n=221) with chronic pulmonary disease, 27.4% (n=219) with renal disease, and 25.0% (n=200) with peripheral vascular disease. Among other comorbidities of interest, anemia (93.7%, n=749) and thrombocytopenia (79.7%, n=637) were the most prevalent, followed by kidney-related conditions such as kidney failure (47.1%, n=376), acute kidney issues (38.7%, n=309), and chronic kidney disease (26.7%, n=213). Most patients (76.0%, n=607) received an initial gilteritinib dose of 120 mg, followed by 12.3% (n=98) who received 80 mg, and 11.8% (n=94) who received other doses. Within 56 days prior to treatment initiation (baseline), 56.0% (n=444) of patients were red blood cell transfusion independent (RBC-TI) and 64.0% (n=514) of patients were platelet transfusion independent (PLT-TI). During the first 8 weeks of follow-up, 74.8% (n=332) of RBC TI and 75.1% (n=386) of PLT TI patients maintained independence, while 26.8% (n=95) of initially RBC transfusion-dependent (RBC-TD) and 30.9% (n=88) of PLT transfusion-dependent (PLT-TD) patients achieved TI. A substantial proportion of patients maintained TI over time. At ≥8 weeks, 63.9% of patients achieved RBC TI and 65.7% achieved platelet TI. These strong results continued across longer durations, with over half of patients remaining transfusion-independent at ≥16 weeks (50.0% for RBC and 50.9% for platelets). Even at ≥24 weeks, a notable 40.5% (RBC) and 41.6% (platelets) sustained TI. Conclusions : In this real-world study of older Medicare beneficiaries with relapsed AML, many patients receiving gilteritinib experienced periods of transfusion independence for both RBCs and platelets, suggesting low transfusion burden.

e18505 Background: The use of allogeneic hematopoietic cell transplantation (alloHCT) is increasing in older adults with acute myeloid leukemia (AML). Although FLT3 tyrosine kinase inhibitor (FLT3-TKI) use for post-alloHCT maintenance is recommended by the NCCN Clinical Practice Guidelines in Oncology for AML (v.1.2025), real-world data in this setting is limited, especially in older adults. Methods: An observational cohort study assessed healthcare resource utilization (HRU), treatment adherence (proportion of days covered [PDC]), and dose modifications among patients with AML who received alloHCT with FLT3-TKI (gilteritinib, midostaurin or sorafenib) maintenance therapy. Patients were identified from Medicare claims databases from Jan 1, 2016–Jun 30, 2024. Index date was the first FLT3-TKI claim within 100 days post alloHCT, with follow up until relapse, death or end of study. Data were summarized descriptively. Results: Of 150 patients, mean age was 70.5 years and Charlson Comorbidity Index score was 4.5. Mean time to FLT3-TKI maintenance initiation was 56.2 days post-alloHCT; 82 (54.7%) received gilteritinib, 36 (24.0%) midostaurin and 32 (21.3%) sorafenib. Relative to patients who received midostaurin or sorafenib, gilteritinib patients were older (57.3% vs. 45.6% ≥70 years) and a greater proportion received low-intensity induction chemotherapy (50.0% vs. 19.1%). A similar proportion of patients had relapsed/refractory (R/R) AML prior to alloHCT; 54.9%, 58.3%, and 46.9% for gilteritinib, midostaurin, and sorafenib, respectively. The greatest HRU overall was outpatient physician visits (mean 3.2 per patient per month), with no differences in either outpatient visits or hospitalizations among treatment groups. Mean PDC was 47% overall (54% gilteritinib, 43% midostaurin and 34% sorafenib); adherence was better for patients with vs. without a history of R/R AML pre-alloHCT at 52% vs. 41%. Rate of dose reductions were low on maintenance with gilteritinib; 84% of patients maintained or increased their gilteritinib dose during follow-up and no gilteritinib dose change was observed in 36.1% and 28.9% of patients with and without a history of R/R AML pre-alloHCT, respectively. Dose modification results were blinded for midostaurin/sorafenib groups. Switching among FLT3-TKIs was also uncommon: all patients initiated on gilteritinib remained on gilteritinib, while <32% and 38% of patients initiated on midostaurin or sorafenib, respectively, switched to an alternative FLT3-TKI. Conclusions: Real-world treatment patterns suggest gilteritinib maintenance is well-tolerated among older adult alloHCT recipients with AML. While the low sample size limits interpretability of some study results, gilteritinib may be associated with improved adherence and tolerability relative to other FLT3-TKIs.

Allogeneic hematopoietic cell transplantation (alloHCT) is used to treat patients with acute myeloid leukemia (AML) with internal tandem duplication of the FMS-like tyrosine kinase 3 gene (FLT3-ITDmut+). However, the effect of different characteristics on outcomes after transplant is not fully understood. The aim of this study was to determine the impact of patient, disease, and transplant characteristics on clinical outcomes and trends in maintenance therapy for patients with FLT3-ITDmut+ AML who underwent their first alloHCT. This was an observational cohort study of adults >= 18 years who were recipients of human leukocyte antigen identical sibling, haploidentical, 8/8 or 7/8 unrelated, or cord blood donor alloHCT in the United States and Canada between 2014 and 2019. Patient, disease, and transplant characteristics were collected from Center for International Blood & Marrow Transplant Research between 2014 and 2022. Patients enrolled in the MORPHO clinical trial (NCT02997202) were excluded. Clinical outcomes were measured from the time of alloHCT by disease status: first complete remission (CR1), second or greater complete remission (>= CR2), or relapsed/refractory (R/R). The primary endpoints of this study were overall survival (OS) and leukemia-free survival (LFS). Key secondary endpoints included relapse after alloHCT, nonrelapse mortality (NRM), time from diagnosis to complete remission, time from complete remission to alloHCT, and maintenance therapy before and after alloHCT. Univariate analyses were conducted with Gray's test and log-rank test, while multivariable analyses were conducted using Cox proportional hazards models. A total of 3147 eligible patients (CR1, n = 2389; >= CR2, n = 340; R/R, n = 418) were included. Most patient, disease, and transplant characteristics were similar between different disease statuses. In univariate analyses, disease status of CR1 compared with >= CR2 or R/R was significantly (P < .001) associated with improved OS and LFS, and decreased probability of relapse; NRM likely differed across cohorts after alloHCT (P = .003). In multivariable analyses, patients with a disease status of >= CR2 and R/R compared with CR1 had significantly shorter OS (hazard ratio [HR] 95% confidence interval [CI], 1.43 [1.19 to 1.72], P = .0001, and 2.14 [1.88 to 2.44], P < .0001, respectively). Patients with a disease status of CR1 at <= 2.6 months had better LFS compared with >= CR2 and R/R (HR [95% CI], 2.03 [1.56 to 2.63], P < .0001 and 3.98 [3.07 to 5.17], P < .0001, respectively). Patients with a >= CR2 or R/R disease status at <= 2.6 months had an increased likelihood of relapse compared with CR1 (HR [95% CI], 2.46 [1.82 to 3.33], P < .0001 and 4.68 [3.46 to 6.34], P < .0001, respectively). Disease status was not significantly associated with NRM. We also identified several additional patient, disease, and transplant characteristics that may have been associated with inferior OS and/or LFS and greater relapse and/or NRM. Maintenance therapy usage after alloHCT increased from 2014 to 2019 primarily due to increased FLT3 inhibitor use. In this largest study to date of patients from the United States and Canada with FLT3-ITDmut+ AML, disease status of CR1 at the time of alloHCT was associated with better clinical outcomes. Additional factors were identified that may also impact clinical outcomes, and in total, have the potential to inform clinical decision-making. (c) 2024 The American Society for Transplantation and Cellular Therapy. Published by Elsevier Inc. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/)

Aim: Androgen receptor pathway inhibitors (ARPIs) prolong metastasis-free survival and overall survival in patients with nonmetastatic castration-resistant prostate cancer (nmCRPC). This study aimed to evaluate real-world treatment patterns, utilization and survival outcomes in patients with nmCRPC. Patients & methods: This retrospective cohort study used Optum database electronic health records of patients with nmCRPC from 1 January 2007 to 31 December 2020 in the US. Results: Of 1955 patients, >80% received androgen-deprivation therapy (ADT) alone or ADT + first-generation nonsteroidal antiandrogen (NSAA) as first-line treatment, while only 8.24% received ADT + ARPI. ADT + ARPI remained underutilized even among those with high-risk nmCRPC. Further, ADT + NSAA had no survival benefit compared with ADT alone. Conclusion: Practice-improvement strategies are needed for treatment intensification with ARPIs for patients with nmCRPC. Plain language summary Prostate cancer cells often use hormones called androgens to grow and survive. Hormone therapy is a treatment that lowers the amount of these hormones in the body to slow down the cancer's growth. It includes androgen-deprivation therapy (ADT), which can either be used alone or along with nonsteroidal antiandrogens (NSAAs) or with androgen receptor pathway inhibitors (ARPIs). Nonmetastatic castration-resistant prostate cancer (nmCRPC) is defined as prostate cancer that has not spread to other parts of the body but exhibits rising levels of serum prostate-specific antigen despite surgery or ADT to reduce androgens. Research shows that ARPIs can improve survival in patients with nmCRPC, but more data on its use are needed. This study looked at the electronic health records of patients with nmCRPC to review the treatment they had received and their survival. Between 2008 and 2020, most patients received ADT alone or with NSAA. Even though the number of patients receiving ADT with ARPI increased during this period, it remained underused, even in patients with a high risk of cancer spreading to other body parts. Post-2018, even after 2 years of these drugs being available, only about one in five patients received ADT with ARPI. Also, people who received ADT with NSAA did not have a longer survival than patients treated with ADT alone. The study indicates that ARPIs, which could improve survival of patients with nmCRPC, are not being utilized optimally. Strategies that promote early use of ARPIs are needed to improve survival of patients with nmCRPC.

Context FMS-like tyrosine kinase 3 inhibitors (FLT3-TKIs) are recommended for post-allogeneic hematopoietic cell transplant (alloHCT) maintenance in patients with acute myeloid leukemia (AML) in the United States (US), but real-world data on patient adherence and persistence are limited. Objective Evaluate adherence/persistence of FLT3-TKI as post-alloHCT maintenance in patients with AML with and without pre-alloHCT relapsed/refractory (R/R) disease. Design/Patients Observational study of US Inovalon Insights payer-sourced claims database. Eligible adult patients with AML received ≥1 alloHCT between 01/01/2016 and 06/30/2022; initiated gilteritinib, midostaurin, or sorafenib as maintenance ≤100 days post-alloHCT; and were followed from FLT3-TKI initiation to earliest post-alloHCT relapse, end of enrollment or study (adherence/persistence), or treatment end (persistence). Main Outcome Measures Adherence (proportion of days covered [PDC] with FLT3-TKI in follow-up period ≥80%) and persistence (days of FLT3-TKI with <60 days treatment gap and without switching agents). Adjusted multivariate regression analyses were conducted. Results Patients (n=162; median age 52.0 [interquartile range: 39.0–60.0] years) received post-alloHCT FLT3-TKI maintenance; 65.4% (106/162) had pre-alloHCT R/R disease. Median PDC for gilteritinib, midostaurin, and sorafenib was 61.6%, 28.9%, 43.2% in patients without and 80.5%, 51.8%, 61.5% in those with pre-alloHCT R/R disease. Patients with pre-alloHCT R/R disease were less likely to be nonadherent than those without (P=0.009). Compared with gilteritinib, nonadherence was numerically greater for patients receiving midostaurin (odds ratio [OR]: 2.1; 95% CI, 0.9–5.0; P=0.097) or sorafenib (OR: 2.0; 95% CI, 0.9-4.7; P=0.099). Kaplan-Meier median days of persistence was 188 for gilteritinib, 51 midostaurin, and 113 sorafenib in patients without and 324, 127, and 155 in patients with pre-alloHCT R/R disease. Adjusted risk of discontinuation was 2.93 times higher for midostaurin (P=0.0003) and 1.75 times higher for sorafenib (P=0.0418) than for gilteritinib. At 18 months after FLT3-TKI initiation, 10.1% patients without and 13.9% with pre-alloHCT R/R disease continued treatment (gilteritinib: 25.6%, 31.9%; midostaurin: 7.6%, 6.5%; sorafenib: 8.6%, 11.4%, respectively). Conclusions Overall real-world adherence to FLT3-TKI was modest, particularly among patients without pre-alloHCT R/R disease, and risk of discontinuation was lowest for gilteritinib regardless of R/R status. Additional studies exploring patient and disease-specific factors most predictive of adherence are warranted.

e23287 Background: Historically, cisplatin-containing chemotherapy has been the recommended first-line (1L) treatment for locally advanced or metastatic urothelial carcinoma (la/mUC). For those ineligible for cisplatin due to poor performance status, impaired renal function, or comorbidities, alternative choices include carboplatin-based chemotherapy and PD-1/L1 inhibitors. This study aimed to describe real-world treatment patterns and overall survival (OS) among US Medicare patients with la/mUC receiving 1L therapy. Methods: This retrospective study used Medicare fee-for-service claims data from 2015 through 2022 to identify patients diagnosed with la/mUC who received systemic treatment. Initiation of 1L therapy was the index date for study inclusion; treatment patterns and OS were assessed until end of data availability, discontinuation of health plan enrollment, or death. OS was estimated using the Kaplan–Meier approach, and a log-rank test was used to compare OS across the following 1L treatment groups: platinum-based chemotherapy (PBC; cisplatin- and carboplatin-based), non-PBC monotherapy, and PD-1/L1 inhibitor monotherapy. Hazard ratios (HRs) were estimated across groups using Cox proportional hazards models adjusting for baseline characteristics. Results: Of 13,104 patients included in this analysis, 77.5% were male, and mean (SD) age was 76.2 (7.5) years. The most commonly observed 1L treatment categories were PBC (cisplatin-based, 19.7%; carboplatin-based, 28.4%), PD-1/L1 inhibitors (34.8%), non-PBC (13.7%), and other combination therapies (2.9%). Common comorbidities included renal disease (39.9%), chronic obstructive pulmonary disease (36.1%), and diabetes (32.2%). Compared with patients in the cisplatin cohort, patients in other cohorts had higher NCI Comorbidity Index scores. Median duration of 1L treatment was 3.5 months for PD-1/L1 inhibitors, 3.2 months for carboplatin, 3.0 months for cisplatin, and 2.0 months for non-PBC. Median OS was longest with cisplatin (17.0 months; IQR: 7.8–51.9), followed by non-PBC (14.7; 5.5–39.7), carboplatin (10.5; 4.9–25.1), and PD-1/L1 inhibitors (9.4; 2.8–27.9). In the adjusted Cox model, all treatment groups had statistically significantly higher hazards of death compared with cisplatin, with an HR (95% CI) of 1.50 (1.41, 1.59; P< 0.001) for PD-1/L1 inhibitors, 1.38 (1.30, 1.46; P< 0.001) for carboplatin, and 1.11 (1.03, 1.19; P= 0.007) for non-PBC. Conclusions: In this large retrospective study of US Medicare patients from 2015–2022 with la/mUC, PBC was the most common 1L treatment, followed by PD-1/L1 inhibitors and non-PBC. While cisplatin-treated patients had longer OS than patients in other groups, treatment durations were short, and OS was generally poor across regimens. These findings highlight an unmet need for more effective 1L therapies in la/mUC.

BACKGROUND:The current guidelines for treating metastatic castration-sensitive prostate cancer (mCSPC) recommend treatment intensification of androgen deprivation therapy (ADT) with the addition of an androgen receptor pathway inhibitor (ARPI), with or without docetaxel. However, the adoption of these treatment options has been slow, leading to therapeutic inertia. This real-world study was conducted to investigate the occurrence of adverse events (AEs) among treated patients diagnosed with mCSPC in the United States. METHODS:This retrospective claim review estimated the occurrence of AEs among patients with mCSPC from January 2014 to June 2021 in the PharMetrics® Plus data set. The study focused on 10 common AEs (fatigue/asthenia, gastrointestinal [GI] AEs, skin/nail/hair AEs, immunodeficiency/thrombocytopenia, hot flash, sexual function AEs, anemia, hypertension, pain, and edema) known to occur in ≥10% of patients and ≥2% more prevalent than those treated with ADT alone as selected from the US Food and Drug Administration prescribing information and published results from clinical trials. Proportions of patients experiencing these AEs at Day 90, 180, and then every 180 days until month 30 during the follow-up period were estimated using cumulative hazard plots. Results were adjusted using inverse probability of treatment weighting (IPTW) across four treatment groups: ADT alone, ADT + nonsteroidal anti-androgen (NSAA) (bicalutamide, nilutamide, or flutamide), ADT + docetaxel, and ADT + ARPIs (abiraterone, apalutamide, or enzalutamide). ADT-alone cohort was the reference group for all comparisons. RESULTS:A total of 4145 patients were included (ADT alone: 2318, ADT + NSAA: 632, ADT + docetaxel: 471, ADT + ARPIs: 724). At baseline, median (interquartile range [IQR]) age was 64.3 (60.1-73.1) years; most common sites of metastasis were bone only (n = 1886, 45.5%) and node only (n = 1237, 29.8%); most used medications were pain medications (n = 2182, 52.6%) and corticosteroids (n = 1213, 29.3%). Median (IQR) duration of follow-up 10.2 (6.1-16.6) months in ADT alone, 6.7 (4.1-11.5) months in ADT + NSAA, 5.1 (4.3-5.9) months in ADT + docetaxel, and 11.0 (6.6-17.0) months in ADT + ARPI cohort. The reported AEs increased over time for all assessed AEs, across all treatment groups. Compared with ADT alone, no statistically significant difference in the proportion of patients with AEs was seen in the ADT + ARPI or ADT + NSAA cohorts at months 3 and 12; a significantly higher proportion of patients in the ADT + docetaxel cohort experienced 6 of the 10 assessed AEs at month 3 (fatigue/asthenia, GI AEs, skin/nail/hair AEs, immunodeficiency/thrombocytopenia, hot flash, anemia). During the follow-up period, on IPTW analysis, compared with ADT alone, a significantly higher proportion of patients experienced AEs with seven AEs in the ADT + docetaxel group (fatigue/asthenia, GI AEs, skin/nail/hair AEs, immunodeficiency/thrombocytopenia, hot flash, anemia, edema; p < 0.001 for all seven), three AEs in the ADT + ARPI group (hot flash, p = 0.05; anemia, p = 0.01; edema, p = 0.019), and one AE in the ADT + NSAA group (anemia, p = 0.029). The proportion of patients with sexual function AE did not significantly differ between the treatment groups and ADT alone. CONCLUSION:Results of this large, real-world study demonstrated that all treatment groups experienced an increase in the rates of AEs over time, including ADT alone. Most AE rates with ADT + ARPIs were comparable with ADT + NSAA and not significantly different from ADT alone. ADT + docetaxel cohort was associated with significantly higher rates for all AEs over time except hypertension, sexual dysfunction, and pain. This study provides real-world evidence on AEs, beyond controlled clinical trials, and may assist healthcare providers to make better-informed decisions about disease management among patients with mCSPC.

ObjectiveWe describe the impact of acute myeloid leukemia (AML) diagnosis on workplace absenteeism and disability days among patients and their caregivers.MethodsThis retrospective study included adults with newly diagnosed AML (2009-2019) and adult caregivers of patients with newly diagnosed AML, identified from the US Merative (TM) MarketScan (R) Commercial Database. The Merative MarketScan Health and Productivity Management Database provided linked patient-level records of workplace absence and short-term (STD) and long-term disability (LTD) data. Endpoints included workplace absence, STD and LTD for patients and caregivers during 12 months pre-AML (baseline) and <= 3 years' follow-up, and corresponding cost of work loss.ResultsPatient workplace absence decreased in the months post-AML diagnosis, but the number of STD and LTD leave days claimed increased significantly by sixfold and fourfold, respectively. The proportion of patients making STD leave claims increased within 4-5 months of diagnosis, while the proportion making LTD leave claims increased significantly starting from month 5. Caregiver workplace absence peaked in the first 2 months post-diagnosis and remained elevated versus baseline throughout the study.ConclusionAML diagnosis leads to workplace absenteeism and increased economic burden for patients with AML and their caregivers.

e19002 Background: Treatment for acute myeloid leukemia (AML) includes intensive chemotherapy and/or hematopoietic stem cell transplant, and patients usually require extended hospital stays and absence from work. Caregivers may also take workplace absence to provide care during and after treatment. As data on the indirect burden of AML are underreported, we aimed to understand the impact of work absenteeism (ABS) and disability days among patients with AML and caregivers. Methods: This non-interventional, retrospective analysis of healthcare claims data was conducted using MarketScan Databases containing ABS data. Two cohorts were analyzed: patients newly diagnosed with AML between January 1, 2009 and December 1, 2019 (index period), and caregivers with an adult family member newly diagnosed with AML during the index period. All participants were full-time employees, aged 18–64 years, and had ≥12 months of continuous enrollment prior to index date and ≥30 days of continuous enrollment after index date. The index date was the date of first AML diagnosis for patients, or the date of the linked family member’s first AML diagnosis for caregivers. Participants were followed for ≥30 days up to 3 years, until the end of continuous enrollment, end of database eligibility, or end of the study period. Participants who were pregnant or in families with > 1 member with AML were excluded. Days of work loss and associated wage loss were calculated for each work loss type: ABS, short-term disability (STD), and long-term disability (LTD). Results: This analysis included 1,037 patients with AML and 781 caregivers. From baseline to follow-up (FU) period, the proportion of patients reporting ABS numerically decreased from 72.8% to 62.7% (p = 0.054), and changes in ABS days per patient per month (PPPM) (2.21– 2.10, p = 0.735) or ABS-related wage loss PPPM ($562–$511, p = 0.516) were not statistically significant. However, the proportion of patients reporting STD and LTD significantly increased (24.6%–50.0%, p < 0.001, and 4.0%–20.0%, p < 0.001, respectively). The number of days PPPM lost due to STD and LTD significantly increased (0.85–4.94, p < 0.001, and 0.24–1.40, p < 0.001), as did STD- and LTD-related wage loss PPPM ($203–$1194, p < 0.001, and $57–$330, p < 0.001). Among caregivers, the proportion reporting ABS and ABS days PPPM were similar between baseline and FU periods (83.2%–83.9%, p = 0.871, and 2.41–2.64, p = 0.315). The proportion of caregivers with STD claims significantly increased (5.4%–11.8%, p < 0.001), and days PPPM lost due to STD and associated wage loss PPPM numerically increased (0.15–0.25, p = 0.057 and $38–$60, p = 0.087). Conclusions: Following AML diagnosis, the proportion of patients with STD and LTD leave increased significantly, while absenteeism did not change significantly. Days of STD leave also increased among caregivers. Future research is needed to determine how work loss varies by AML treatment type and/or sequencing.

Introduction: Central nervous system (CNS) involvement in acute myeloid leukemia (AML) has been understudied due to the lack of guidelines for screening and treating in this population.In this study, we evaluated the treatments and outcomes of CNS AML patients at two large academic institutions.Methods: Patients with CNS AML were retrospectively identified at Mount Sinai Hospital and the University of Kansas Medical Center.CNS AML was defined as the presence of leukemic blasts in the cerebral spinal fluid (CSF) or atypical immature myeloid cells in the CSF with either suspicious imaging findings and/or neurologic symptoms.Descriptive statistics were employed, and the Kaplan-Meier method was used for survival analysis.Results: A total of 52 adult patients were identified.Features associated with CNS AML included monocytic differentiation (40%), elevated LDH (67%), white blood cells >100K (37%), and FLT3 mutation (46%).Neurologic symptoms were reported in 69% of patients, with headache as the most common (33%), followed by vision changes (25%) and radicular pain (10%).Ninety percent of patients received at least one dose of intrathecal (IT) methotrexate, 71% at least one dose of IT cytarabine, and 65% at least one dose of both.The median number of IT doses received was 4 (range 0-31).Eighty-four percent of patients achieved CSF clearance, with a median number of IT doses required for clearance of 1 (range 1-9).Of these patients, 21% had a CSF relapse with 67% of those with CSF relapse having concurrent bone marrow relapse.Of the 36 patients with baseline neurologic symptoms, 69% had improvement in symptoms post-IT therapy.The median overall survival was 9.3 months and 3.5 months for patients with CNS involvement diagnosed before/during induction and after induction, respectively.Discussion: In this study, IT therapy was shown to be rapidly effective in clearing CSF blasts and improving neurologic symptoms in most patients.Few patients experienced CSF relapse which typically occurred with concomitant bone marrow relapse.Prospective trials and larger multi-institutional collaborations are needed to inform better the optimal surveillance and treatment of CNS involvement in AML.

109 Background: Treatment options for mCSPC patients include adding novel hormonal therapy (NHT) with/without docetaxel (DOC) to androgen deprivation therapy (ADT). Uptake of these agents has been slow, and safety concerns may contribute to therapeutic inertia. This study aims to understand the RW occurrence of prespecified AEs among pts with mCSPC in the US. Methods: Claims from the PharMetrics Plus database (IQVIA, Durham, NC) were used to retrospectively estimate the proportion of pts with AEs among those with mCSPC from Jan 2014 through Jun 2021. Common AEs (≥10%) specified in FDA labels of treatments of interest or clinical trials ≥2% more prevalent than ADT alone were included in the study. Results of four clinically important AEs (fatigue, hot flash, sexual function and gastrointestinal [GI] AEs) are reported here. The proportions of pts with each of these AEs at specific timepoints plus 95% confidence intervals (CI) were estimated from cumulative hazard plots. Results were adjusted using inverse probability of treatment weighting across ADT alone, ADT+ nonsteroidal antiandrogen (NSAA), ADT+DOC and ADT+NHT. Results: The mean age of the overall study population (N=4145) was 66 years. At baseline, common sites of metastasis were bone only (n=1886, 45.5%) and node only (n=1237, 29.8%); the most common medications used were for pain (n=2182, 52.6%) and corticosteroids (n=1213, 29.3%). The reference group for all comparisons of AEs was ADT alone. For the entire study period, GI AEs and fatigue were significantly higher only in the ADT+DOC group ( P<0.001). Hot flash was higher in ADT+NHT ( P=0.05) and the ADT+DOC groups ( P<0.001). No statistically significant differences in sexual function AEs in the groups was noted. The table shows the proportions of pts with specified AEs. Conclusions: In this large RW study, all groups, including ADT alone, showed an increase in AE reporting over time. Most AE rates with ADT+NHT were comparable to ADT alone and ADT+NSAA, while ADT+DOC showed an increase in GI AEs, fatigue and hot flash. [Table: see text]