Ciltacabtagene autoleucel (cilta-cel), is a B-cell maturation antigen-directed, genetically modified autologous chimeric antigen receptor T-cell (CAR-T) immunotherapy. It is indicated for treatment for adult patients with relapsed or refractory multiple myeloma (RRMM) after four or more prior lines of therapy, including a proteasome inhibitor, an immunomodulatory agent, and an anti-CD38 monoclonal antibody. The objective of this study was to estimate the per-patient US commercial healthcare costs related to cilta-cel (CARVYKTI®) CAR-T therapy (i.e., costs separate from cilta-cel therapy acquisition) for patients with RRMM. US prescribing information for cilta-cel, publicly available data, and published literature were used with clinician input to identify the cost components and unit costs associated with administration of cilta-cel. Cost components included apheresis, bridging therapy, conditioning therapy, administration, and postinfusion monitoring for 1 year of follow-up. Adverse event (AE) management costs for all grades of cytokine release syndrome and neurologic toxicities, and additional AEs grade ≥ 3 occurring in > 5

The treatment of multiple myeloma (MM) remains a challenge as patients eventually progress through several lines of therapy (LOTs), requiring use of multiple MM drug classes. In this retrospective US claims-database study, we examined the healthcare costs of patients with MM who received ≥ 4 prior LOTs, including triple-class exposure (TCE). Adult patients with MM were selected from the IBM MarketScan Commercial and Medicare claims databases (1 January 2012–30 June 2021). Eligible patients were required to have received at least four prior LOTs, and TCE (i.e., received a proteasome inhibitor, immunomodulatory drug, and anti–CD38-targeted monoclonal antibody) after the first-observed diagnosis of MM. The index date was defined as the initiation date of the first subsequent LOT after meeting the eligibility criteria for the study, and this date had to be after 1 January 2017 to capture contemporary cost estimates. The primary outcome measurements were all-cause and MM-related healthcare costs after the index date. The study population included 68 patients with MM (63

Chimeric antigen receptor T-cell (CAR-T) therapies targeting the B-cell maturation antigen are a new class of therapy for treating Relapsed or Refractory Multiple Myeloma (RRMM). As CAR-T therapies are introduced, payers will need to balance the higher efficacy, upfront costs, and total treatment costs when evaluating potential value. We developed a cost per responder (CPR) model which incorporates efficacy and total treatment cost to evaluate the value of RRMM CAR-T therapies (ciltacabtagene autoleucel [cilta-cel] and idecabtagene vicleucel [ide-cel]). Without available head-to-head trial data, unanchored matching adjusted indirect comparisons (MAIC) were used to evaluate the comparative efficacy of cilta-cel and ide-cel in the CPR model. MAIC results indicated that cilta-cel was associated with statistically significant improved overall response rate (odds ratio [OR]: 94.93 [95% confidence interval [CI]: 21.86, 412.25; p<.0001]), complete response or better rate (OR: 5.65 [95% CI: 2.51, 12.69; p<.0001]) and progression-free survival (PFS) (hazard ratio: 0.37 [95% CI: 0.24, 0.59; p<.0001]) when compared with ide-cel. To estimate total treatment costs, the CPR analysis also included the cost of apheresis, bridging therapy, CAR-T acquisition and administration, supportive care and monitoring, adverse event management, and any costs associated with delivery of inpatient or outpatient clinical services. A time horizon of approximately 31 months was used based on follow-up times available from the CARTITUDE-1 and KarMMa clinical trials. Preliminary results indicate that ide-cel is associated with an approximate cost per overall responder of $763,000, cost per complete responder of $1,710,000, and cost per month in PFS of $50,000. Corresponding results for cilta-cel will be generated closer to the PDUFA date (February 28, 2022) and presented at ISPOR 2022. CPR models have significant potential to support payers in evaluating the value of newer, more innovative RRMM therapies by incorporating information on both treatment efficacy and total costs.

Proteasome inhibitors (PIs) and immunomodulatory drugs (IMiDs) have significantly improved survival in Multiple Myeloma (MM) patients, but patients continue to progress or become refractory to these treatments, requiring the use of additional lines of therapy (LOTs). This retrospective study assessed real world healthcare resource utilization (HCRU) and subsequent costs in MM patients in the United States, after receiving 1-3 LOTs, exposed to a PI and an IMiD, and exposed to (and discontinued) lenalidomide.

Background: Chimeric antigen receptor T-cell (CAR-T) therapy represents a new frontier in multiple myeloma. It is important to understand critical success factors (CSFs) that may optimize its use in this therapeutic area. Methods: We estimated the CAR-T process using time-driven activity-based costing. Information was obtained through interviews at four US oncology centers and with payer representatives, and through publicly available data. Results: The CAR-T process comprises 13 steps which take 177 days; it was estimated to include 46 professionals and ten care settings. CSFs included proactive collaboration, streamlined reimbursement and CAR-T administration in alternative settings when possible. Implementing CSFs may reduce episode time and costs by 14.4 and 13.2%, respectively. Conclusion: Our research provides a blueprint for improving efficiencies in CAR-T therapy, thereby increasing its sustainability for multiple myeloma.

Chimeric antigen receptor T (CAR-T) cell therapies are newly developed treatments for relapsed refractory multiple myeloma (RRMM) patients who have been triple-class exposed (i.e., proteasome inhibitors, immunomodulatory agents, and monoclonal antibodies during treatment). CAR-T acquisition costs are known and readily available, however other costs associated with CAR-T therapy, such as the required pre-, peri-, and post-infusion costs are unknown. This study estimated healthcare costs related to CAR-T therapy (i.e., costs separate from CAR-T therapy acquisition) for RRMM patients.

8045 Background: Pts with RRMM who are triple-class exposed (to immunomodulatory drugs [IMiDs], proteasome inhibitors [PIs] and an anti-CD38 antibody) cycle through multiple salvage regimens with progressively worse outcomes. CARTITUDE-1 (NCT03548207) is a single-arm phase 1b/2 study evaluating cilta-cel, a chimeric antigen receptor T-cell therapy with 2 B-cell maturation antigen–targeting single-domain antibodies, in pts with RRMM who received ≥3 prior lines of therapy (LOT) or were double refractory to an IMiD and PI, were triple-class exposed, had ECOG score of 0 or 1, and had disease progression ≤12 mo after the last LOT. Here, we compare efficacy outcomes for pts who received cilta-cel in CARTITUDE-1 (N = 97) with pts treated with SOC in a synthetic cohort from RW clinical practice. Methods: The Flatiron database, a primarily US community-based MM registry (Sep 2020 data cutoff), was used to identify a RW pt cohort who met CARTITUDE-1 (Sep 2020 data cutoff) eligibility criteria, including organ function. Progression-free/overall survival (PFS/OS) were compared between the cilta-cel–treated US pts and RW SOC cohort, using inverse probability of treatment (tx) weighting (IPTW) propensity scores adjusting for unbalanced baseline covariates of prognostic significance. Sensitivity analyses were conducted using multivariate Cox regression models and propensity score matching. Results: Baseline characteristics were similar between the 2 cohorts after propensity score weighting (Table). SOC tx regimens in the RW cohort primarily included pomalidomide (33%), carfilzomib (32%), daratumumab (13%), elotuzumab (16%), and ixazomib (8%). Pts had improved PFS and OS with cilta-cel (N = 97; median follow-up 12.4 mo) vs RW SOC (N = 196; median follow-up 9.2 mo) with a reduction in risk of progression/death and death by 84% and 78%, respectively (Table). Cilta-cel treatment benefit was robust across sensitivity analyses. Conclusions: Cilta-cel shows significantly better efficacy outcomes over RW SOC for PFS and OS, highlighting its potential as an effective tx option in pts with triple-class exposed RRMM. Clinical trial information: NCT03548207. [Table: see text]

CAR-T therapies represent a novel advance in oncology, albeit at list prices that exceed $373,000 (and that does not capture their total cost to the healthcare system). Since initial product approval in 2017, stakeholders and observers have attempted to investigate clinical and financial impacts of CAR-T therapies, and potential approaches to optimizing access and use by eligible patients. Most existing research is from a single stakeholder perspective - patients, providers, or payers - limiting the ability to draw broader conclusions on trends and offer prospective recommendations. To address this knowledge gap, we sought to identify and describe critical success factors for optimal delivery of CAR-T therapies. We undertook a qualitative study based on interviews with multiple US-based stakeholders including clinicians, financial and operations staff, and payer-insurers. Interviewees--which included oncologists (n=6), facility financial and operational personnel (n=4), and coverage and reimbursement decision-makers from US health plans (n=3)--completed structured, live, hour-long, interviews covering clinical, administrative, and general topics on patient access to CAR-T therapies. All clinicians had experience with ≥1 FDA-approved CAR-T therapies in both registered clinical trials and clinical practice; financial and operational personnel were affiliated with the same facilities as the clinicians, and also had real-world experience with these therapies; payer representatives were directors from a large national commercial plan, regional integrated delivery network, and a Medicare administrative contractor, respectively. Consensus facility feedback (i.e., clinicians, operational personnel) was that CAR-T is effective, and that their administrative processes had been optimized through care team coordination and experience-based efficiencies; in contrast, 2 of 3 payer interviewees expressed that, while CAR-T therapies have shown efficacy, their real-world benefits and applicability are less well-defined. Facility interviewees noted that: (1) reimbursement from commercial insurers is higher than from Medicare, with the latter associated with per-patient net-neutral or negative margins; (2) when possible, differential reimbursement between inpatient and outpatient settings may drive patient management towards outpatient care; and (3) negative-margin cases are currently deemed acceptable due to nonclinical factors (i.e., competitive pressure within a geographic region, anticipated branding/marketing value) and relatively small treated populations. From payer interviewees, CAR-T cost and perceived cost-to-value have made health plans more receptive to considering outcomes-based contracting, capitated provider payments, or other mitigation methods. Left unoptimized, these factors may adversely impact patient access to, and long-term provider attractiveness of, CAR-T therapies. All interviewees agreed that as the CAR-T marketplace grows, a strong preference exists for manufacturers to develop and communicate for their therapies durable outcomes data, clear and comprehensive reimbursement information, and competitive pricing. With the potential for many approved products in a single indication, and/or a single approval for indications with relatively large eligible patient populations, interviewees also conveyed interest in compelling health economic data. Facility interviewees also acknowledged that if it remains an overall net-negative margin service, new providers will be less able to start CAR-T programs and smaller programs may encounter sustainability issues, collectively jeopardizing patient access to these life-changing therapies. Overall, findings from this study suggest that during the continued maturation of the landscape, stakeholders will need to be proactive to ensure that CAR T-cell therapies can be maintained amidst financial and operational pressures. Several CAR-T therapy options for multiple myeloma are on the immediate horizon, likely increasing demand among eligible patients. Accordingly, the need to link real-world evidence of the clinical value and institutional investment burden of these therapies to reimbursement is imperative, both to insulate payers and enable clinicians to provide innovative therapies. Figure 1 Figure 1. Faber: Amgen: Honoraria; Adaptive: Honoraria; Cardinal Health: Honoraria; Celgene: Honoraria; Astra Zeneca: Honoraria; GlaxoSmith Kline: Honoraria; Janssen: Honoraria; Juno: Honoraria; Karyopharm: Honoraria; Kite: Honoraria; Takeda: Honoraria; Sanofi Genzyme: Honoraria. Hunter: BMS: Consultancy, Honoraria; Kite: Consultancy, Honoraria, Speakers Bureau; Novartis: Consultancy, Honoraria. Deol: Kite, a Gilead Company: Consultancy. Crivera: Johnson & Johnson: Current Employment, Current equity holder in publicly-traded company. Riccobono: Legend Biotech: Current Employment, Current holder of individual stocks in a privately-held company, Current holder of stock options in a privately-held company. Garrett: Legend Biotech USA: Current Employment. Jackson: Memorial Sloan Kettering Cancer Center: Consultancy; Janssen: Current Employment. Fowler: Amgen: Ended employment in the past 24 months; Janssen: Current Employment. Berger: Janssen Scientific Affairs: Consultancy, Research Funding. Lorden: Janssen Scientific Affairs: Consultancy, Research Funding. Stewart: Janssen Scientific Affairs: Consultancy, Research Funding.

Background and Objective Registrational trials for ciltacabtagene autoleucel [cilta-cel]) and idecabtagene vicleucel [ide-cel] chimeric antigen receptor T-cell (CAR-T) therapies were single-arm studies conducted with relapse refractory multiple myeloma (MM) patients who were triple-class-exposed (TCE) or triple-class-refractory (TCR). It is critical for researchers conducting comparative effectiveness research (CER) to carefully consider the most appropriate data sources and comparable patient populations. The aim of this study was to identify potential data sources and populations for comparing to single-arm CAR-T trials CARTITUDE-1 (cilta-cel) and KarMMa (ide-cel). Methods A 2-part global systematic literature search produced a review of (1) clinical trials of National Comprehensive Cancer Network (NCCN) guideline preferred regimens in previously treated MM, and (2) real-world data cohorts of TCE or TCR populations, published between 1/1/2015 and 12/10/2020, with sample sizes of > 50 patients and reporting survival-related outcomes. Implications on CER and accepted best practices are discussed. Results Nine clinical trials of NCCN preferred regimens were identified along with five real-world data-based publications. No clinical trials evaluated patients with TCE or TCR MM. Among the real-world data-based publications, two evaluated patients exclusively with TCR MM, two analyzed a mixed population of patients with TCE or TCR MM, and one publication assessed patients exclusively with TCE MM. Real-world data treatment patterns were heterogeneous. Conclusion Current NCCN preferred regimens were not specifically studied in TCE or TCR MM patients, although some studies do include a proportion of these types of patients. Therefore, appropriate matching of populations using either real-world data or patient level clinical trial data is critical to putting trials of novel CAR-Ts (i.e., CARTITUDE-1 or KarMMa) into appropriate comparative context.

Traditional statistical techniques for extrapolating short-term survival data for anticancer therapies assume the same mortality rate for noncured and “cured” patients, which is appropriate for projecting survival of non-curative therapies but may lead to an underestimation of the treatment effectiveness for potentially curative therapies. Our objective was to ascertain research trends in survival extrapolation techniques used to project the survival benefits of chimeric antigen receptor T cell (CAR-T) therapies. A global systematic literature search produced a review of survival analyses of CAR-T therapies, published between January 1, 2015 and December 14, 2020, based on publications sourced from MEDLINE, scientific conferences, and health technology assessment agencies. Trends in survival extrapolation techniques used, and the rationale for selecting advanced techniques, are discussed. Twenty publications were included, the majority of which (65%, N = 13) accounted for curative intent of CAR-T therapies through the use of advanced extrapolation techniques, i.e., mixture cure models [MCMs] (N = 10) or spline-based models (N = 3). The authors’ rationale for using the MCM approach included (a) better statistical fits to the observed Kaplan–Meier curves (KMs) and (b) visual inspection of the KMs indicated that a proportion of patients experienced long-term remission and survival which is not inherently captured in standard parametric distributions. Our findings suggest that an advanced extrapolation technique should be considered in base case survival analyses of CAR-T therapies when extrapolating short-term survival data to long-term horizons extending beyond the clinical trial duration. Advanced extrapolation techniques allow researchers to account for the proportion of patients with an observed plateau in survival from clinical trial data; by only using standard-partitioned modeling, researchers may risk underestimating the survival benefits for the subset of patients with long-term remission. Sensitivity analysis with an alternative advanced extrapolation technique should be implemented and re-assessment using clinical trial extension data and/or real-world data should be conducted as longer-term data become available.

Multiple myeloma (MM) is a malignancy of plasma cells; most MM patients will eventually relapse or become refractory to treatment. Treating MM patients remains a challenge since patients eventually progress through several lines of therapy (LOTs), requiring the use of multiple MM drug classes. We examined healthcare resource utilization (HCRU) and the costs incurred by MM patients following triple class exposure (TCE; defined as exposure to a proteosome inhibitor, an immunomodulatory agent, and an anti-CD-38 antibody). Adult MM patients were selected from the MarketScan® commercial and Medicare supplemental databases (January 2009–February 2021). From this cohort, patients who had TCE and ≥ 1 subsequent LOT that occurred after January 1, 2017 were included in the study population. The initiation date for the first post-TCE LOT was defined as the index date. All-cause and MM-related HCRU and the associated costs were examined post-index date. A total of 85 MM patients with TCE who initiated ≥ 1 subsequent LOT post-TCE and had ≥ 1 year of follow-up post-index date were included in the study population; mean age on index date was 58.8 years, and 60.0% were male. The time from first-observed MM diagnosis until index date averaged 47.5 months. During an average follow-up of 20.9 months post-index date, 64.7% of patients (N = 55) initiated a second LOT and 35.2% (N = 30) received at least 3 LOTs. During follow-up, mean total all-cause healthcare cost per patient was $722,992 (equivalent to $34,578 per patient per month [PPPM]). Approximately 90.7% ($655,524 per patient) of the total all-cause healthcare costs were MM related, 66.0% of which were MM drug/infusion costs. In this real-world US study, MM patients with TCE incurred high healthcare costs, with the majority being MM related and primarily attributed to MM drug and infusion costs.

New classes of therapies have emerged for treating Relapsed or Refractory Multiple Myeloma (RRMM) patients, including chimeric antigen receptor T-cell (CAR-T) therapies targeting the B-cell maturation antigen. While CAR-T therapies are expected to be a more expensive class of treatment compared to chemotherapy, 1 they have been shown to have a high overall response rate (ORR) and progression-free survival (PFS). 2,3 As newer, more innovative RRMM therapies are developed and brought to market, payers will need to balance their higher efficacy and total treatment costs when assessing potential value. To assess the value of RRMM CAR-T therapies (ciltacabtagene autoleucel [cilta-cel] and idecabtagene vicleucel [ide-cel]), we developed a cost per responder (CPR) model that incorporates efficacy and total cost of treatment.

Abstract Background: Chimeric antigen receptor T (CAR-T) cell therapy is a recent treatment option for triple-class exposed relapsed refractory multiple myeloma (RRMM) patients, who have previously received proteasome inhibitors, immunomodulatory agents, and monoclonal antibodies. In addition to CAR-T cell therapy acquisition costs, there are expected CAR-T healthcare costs separate from the cost of the CAR-T cell therapy itself. Identification and quantification of these costs have not previously been fully investigated. Healthcare payers, hospitals, and physicians need this important cost information in order to make informed healthcare decisions. Objective: The objective of this study was to quantify CAR-T therapy associated healthcare costs, i.e., costs aside from CAR-T therapy acquisition costs, associated with use of CAR-T therapy in RRMM patients. Methods: RRMM CAR-T clinical trial data and published literature, including peer-reviewed publications and conference presentations, were used for identification of these additional healthcare cost components. Inclusion/exclusion of additional cost components was based on previously published oncology pharmacoeconomic studies and input from key opinion leaders (KOLs) with expertise in the treatment of RRMM patients. The study categorized costs for RRMM patients who receive the CAR-T infusion. Costs were categorized as pre-infusion, peri-infusion (excluding CAR-T therapy acquisition costs), and post-infusion costs. Pre-infusion costs included evaluation costs, apheresis costs, bridging therapy costs, and conditioning therapy costs. Peri-infusion costs included either inpatient or outpatient infusion costs. Post-infusion costs included 100-day post-infusion monitoring costs, additional infusion monitoring costs in the first year, and management of serious adverse event (AE) costs associated with the CAR-T therapy. Serious AEs included AEs that require or prolong hospitalization or result in death. CAR-T acquisition costs are known and readily accessible, but this is not the case for other costs associated with CAR-T therapy, i.e., the pre-, peri-, and post-infusion costs. The costs must be individually calculated utilizing CAR-T clinical trial data, medical resource costs and utilization, and AE costs and rates. Based on a targeted literature review, there are sufficient data in the public domain to quantify the component additional costs, however there are no publications quantifying the entirety of these costs specifically in RRMM patients receiving CAR-T. Methodology was developed for derivation of these costs, which comprise an important and consequential portion of the total CAR-T therapy costs. Results: The RRMM patient pre- and peri-infusion CAR-T healthcare cost, aside from CAR-T therapy acquisition costs, was estimated to be $15,478. The components of this cost were apheresis ($112), bridging therapy ($8,570), conditioning therapy ($3,435), and a single day of inpatient infusion ($3,362). The post-infusion costs (including additional inpatient hospital days, AE management, and monitoring costs) are dependent on the types and rates of AEs associated with CAR-T therapy. These results will be presented at the ASH 2021 meeting. Conclusions: This study developed a methodology for the categorization, quantification, and calculation of the important healthcare costs, aside from CAR-T therapy acquisition costs, associated with the use of CAR-T in triple-class exposed RRMM patients. This information has been lacking in the literature and the analysis provides valuable, holistic information that key stakeholders require to make informed decisions. Disclosures Jagannath: Bristol Myers Squibb: Consultancy; Janssen Pharmaceuticals: Consultancy; Karyopharm Therapeutics: Consultancy; Legend Biotech: Consultancy; Takeda: Consultancy; Sanofi: Consultancy. Joseph: Johnson and Johnson: Current Employment, Current equity holder in publicly-traded company. Crivera: Johnson & Johnson: Current Employment, Current equity holder in publicly-traded company. Jackson: Janssen: Current Employment; Memorial Sloan Kettering Cancer Center: Consultancy. Valluri: Janssen: Current Employment, Current equity holder in publicly-traded company. Cost: Johnson & Johnson: Current Employment, Current equity holder in publicly-traded company. Phelps: Johnson & Johnson: Current Employment, Current equity holder in publicly-traded company. Slowik: Johnson & Johnson: Current Employment, Current equity holder in publicly-traded company. Klein: Medical Decision Modeling Inc.: Current Employment. Yu: Medical Decision Modeling Inc.: Current Employment. Smolen: Medical Decision Modeling Inc.: Current Employment. Cohen: GlaxoSmithKline: Consultancy, Research Funding; Janssen: Consultancy; Takeda: Consultancy; Oncopeptides: Consultancy; BMS/Celgene: Consultancy; AstraZeneca: Consultancy; Genentech/Roche: Consultancy; Novartis: Research Funding.

Abstract Introduction Ciltacabtagene autoleucel (cilta‐cel) is a novel chimeric antigen receptor T‐cell therapy that is being evaluated in the CARTITUDE‐1 trial (NCT03548207) in patients with relapsed or refractory multiple myeloma (RRMM) who received as part of their previous therapy an immunomodulatory drug, proteasome inhibitor, and an anti‐CD38 monoclonal antibody (i.e., triple‐class exposed). Given the absence of a control arm in CARTITUDE‐1, this study assessed the comparative effectiveness of cilta‐cel and physician's choice of treatment (PCT) using an external real‐world control arm from the Flatiron Health multiple myeloma cohort registry. Methods Given the availability of individual patient data for cilta‐cel from CARTITUDE‐1 and PCT in Flatiron, inverse probability of treatment weighting was used to adjust for unbalanced baseline covariates of prognostic significance: refractory status, cytogenetic profile, International Staging System stage, time to progression on last regimen, number of prior lines of therapy, years since diagnosis, and age. Comparative effectiveness was estimated for progression‐free survival (PFS), time to next treatment (TTNT), and overall survival (OS). A range of sensitivity analyses were conducted. Results Baseline characteristics were similar between the two cohorts after propensity score weighting. Patients with cilta‐cel had improved PFS (HR: 0.18 [95% CI: 0.12, 0.27; p < 0.0001]), TTNT (HR: 0.15 [95% CI: 0.09, 0.22; p < 0.0001]), and OS (HR: 0.25 [95% CI: 0.13, 0.46; p < 0.0001]) versus PCT. Cilta‐cel treatment benefit was robust and consistent across all sensitivity analyses. Conclusion Cilta‐cel demonstrated significantly superior effectiveness over PCT for all outcomes, highlighting its potential as an effective therapy in patients with triple‐class exposed RRMM.

Objective: Patients with cancer are at high risk for developing primary but also recurrent venous thromboembolism (VTE). This study examined healthcare utilization (HRU) and costs related to VTE recurrence among cancer patients.Methods: Medical and pharmacy claims from the Humana Database were used to compare HRU (outpatient visits, emergency room visits, hospitalizations, and hospitalization days) and healthcare costs among cancer patients with a single VTE event (between 01/2013 and 06/2015) and those with recurrent VTE during the follow-up period (from initiation of anticoagulant therapy until end of eligibility or data availability). All-cause and VTE-related HRU and costs were evaluated using Poisson regression, and healthcare costs were compared using mean differences reported as per-patient-per-year (PPPY).Results: Of 2,428 newly diagnosed cancer patients who developed VTE, 413 (17.1%) experienced recurrent VTE during the follow-up period (mean = 9 months). Patients with recurrent VTE had higher all-cause and VTE-related HRU and costs compared to those without recurrence. Patients with recurrent VTE also had over 3.19-times more VTE-related hospitalizations (RR [95% CI] = 3.19 [2.93-3.47]), and 3.88-times more VTE-related hospitalization days (RR [95% CI] = 3.88 [3.74-4.02]) than patients without a VTE recurrence. Total VTE-related healthcare costs were $39,641 PPPY among patients with recurrent VTE, $29,142 higher compared to those without recurrence ($10,499 PPPY). This difference was mainly driven by hospitalization costs.Conclusion: Recurrent VTE among cancer patients is associated with significant HRU and healthcare costs, notably hospitalizations. Strategies to reduce VTE recurrence in patients with cancer can contribute to reducing healthcare cost.

e20539 Background: MM patients undergo several lines of treatment (LOT), mainly involving ≥1 proteasome inhibitor (PI), immunomodulatory (IMiD), and novel agents such as daratumumab (dara). Research is underway to address the need of patients previously exposed to a PI, an IMiD, and dara (triple-exposed). This retrospective cohort analysis assessed costs and healthcare resource (HR) utilization in triple-exposed patients. Methods: A pooled cohort of patients from Optum’s Humedica Electronic Health Records and Clinformatics claims data with an index MM diagnosis between 2008-2018 and who 1) had ≥12 months of activity/insurance coverage prior to index MM diagnosis, 2) did not have any other cancer during this period, 3) were aged ≥18 years at index diagnosis, 4) were triple exposed and 5) had ≥1 LOT subsequent to triple-exposure were studied. Costs per LOT after triple-exposure, broken down into cost categories, were analyzed in patients from Optum claims data (N = 94), while HR utilization (hospitalization, ER/outpatient visits, lab tests and MM drugs) was analyzed in the pooled cohort (N = 517). Descriptive statistics are reported. Results: 53% of patients were male; mean follow-up was 8.9 months (272 days). At LOT1 following triple-exposure, mean age was 68 yrs, mean time from index MM diagnosis was 37 months, and median prior LOTs were 4. 50% were penta-exposed (2 PIs + 2 IMiDs + dara) following triple exposure. 42% received a pomalidomide-containing regimen in LOT1 after triple-exposure. 56% of patients had ≥2 LOTs after triple-exposure; 28% had ≥3. Mean duration of LOT1, LOT2, and LOT3 in claims data patients was 132, 102 and 101 days, respectively, with associated mean cost per LOT of $165,453, $131,759, and $116,915. Over the follow-up, patients had a mean of 1.75 hospitalizations, 0.92 ER visits, 32.1 outpatient/office visits and 28.8 lab tests; post triple-exposure mean cost per patient per month was $38,214 (Table). Conclusions: Substantial MM drug costs, inpatient stays and frequent outpatient visits contribute to high cost per month of post triple-exposure treatment, underscoring the need for effective MM treatments with durable response. [Table: see text]

Critical limb ischemia (CLI) is a severe stage of peripheral arterial disease and has a substantial disease and economic burden not only to patients and families, but also to the society and healthcare systems. We aim to develop a personalized prediction model that utilizes baseline patient characteristics prior to CLI diagnosis to predict subsequent 1-year all-cause hospitalizations and total annual healthcare cost, using a novel Bayesian machine learning platform, Reverse Engineering Forward Simulation™ (REFS™), to support a paradigm shift from reactive healthcare to Predictive Preventive and Personalized Medicine (PPPM)-driven healthcare. Patients ≥ 50 years with CLI plus clinical activity for a 6-month pre-index and a 12-month post-index period or death during the post-index period were included in this retrospective cohort of the linked Optum-Humedica databases. REFS™ built an ensemble of 256 predictive models to identify predictors of all-cause hospitalizations and total annual all-cause healthcare costs during the 12-month post-index interval. The mean age of 3189 eligible patients was 71.9 years. The most common CLI-related comorbidities were hypertension (79.5%), dyslipidemia (61.4%), coronary atherosclerosis and other heart disease (42.3%), and type 2 diabetes (39.2%). Post-index CLI-related healthcare utilization included inpatient services (14.6%) and ≥ 1 outpatient visits (32.1%). Median annual all-cause and CLI-related costs per patient were $30,514 and $2196, respectively. REFS™ identified diagnosis of skin and subcutaneous tissue infections, cellulitis and abscess, use of nonselective beta-blockers, other aftercare, and osteoarthritis as high confidence predictors of all-cause hospitalizations. The leading predictors for total all-cause costs included region of residence and comorbid health conditions including other diseases of kidney and ureters, blindness of vision defects, chronic ulcer of skin, and chronic ulcer of leg or foot. REFS™ identified baseline predictors of subsequent healthcare resource utilization and costs in CLI patients. Machine learning and model-based, data-driven medicine may complement physicians’ evidence-based medical services. These findings also support the PPPM framework that a paradigm shift from post-diagnosis disease care to early management of comorbidities and targeted prevention is warranted to deliver a cost-effective medical services and desirable healthcare economy.

e20543 Background: Recent advances in medical treatments have improved survival in multiple myeloma (MM), but relapse is a near certainty. TCE MM patients, i.e. treated with a proteasome inhibitor (PI), an immunomodulatory agent (IMiD), and anti-CD38, have been shown to have improved outcomes compared to patients with prior regimens, but patients who subsequently relapse have limited options. Objective: To describe the course of treatment in a real-world, TCE sample of patients with MM with an emphasis on treatments occurring after triple-exposure. Methods: This retrospective descriptive study used 100% Medicare Fee-for-Service claims data and Inovalon’s MORE² Registry, a commercial multi-payor claims database, to identify patients ≥ 18 years of age, newly diagnosed with MM in 2009-2017, and with ≥ 12 months continuous enrollment post-diagnosis. Patients with ≥ 3 lines of treatment (LOT) were considered relapsed/refractory MM (RRMM), and the TCE subset of those were analyzed in terms of number and timing of LOT. Results: 9534 patients were identified with RRMM and 29.2% (N = 2787) were TCE. TCE patients had a mean age of 70.8 and 50.1% were male. Treatment characteristics are shown in Table. Median number of LOT prior to TCE was 3, median time from diagnosis to TCE was 37 months, and 27.3% had a stem-cell transplant (SCT) prior to TCE. Patients had a median of 10 months of follow-up (range: 0-35) from end of the TCE LOT to end of follow-up. Nearly half (N = 1290, 46.3%) of the patients had at least 1 LOT post TCE, and 8% had at least 3. Over their entire post-TCE course of treatment, 826 (64%) received daratumumab, 443 (34%) received carfilzomib, and 356 (28%) received pomalidomide. 35.5% proceeded to penta-exposure (2 different PIs, 2 different IMiDs and an anti-CD38). Conclusions: While triple-exposure drug regimens have demonstrated improved outcomes, nearly half of the patients in this study received additional treatments beyond TCE and over 1/3 progressed to penta-exposure. Given the findings of this study, fundamentally new approaches are needed to close the gap and unmet medical need. [Table: see text]

Introduction The first pass effect (FPE) is the ability to restore near or complete revascularization (modified Thrombolysis in Cerebral Ischemia [mTICI] ≥2c) of acutely blocked cerebral arteries in a single thrombectomy device pass. FPE has been shown to be an independent predictor of good functional outcomes (modified Rankin Scale [mRS] ≤2), a goal of stroke therapy that impacts healthcare costs, and is associated with reduced 90-day mortality and fewer adverse events. A separate analysis of ARISE-II data showed that the FPE was associated with reduced procedural and in-patient healthcare resource use (length of stay, days in the intensive care unit, standard bed days, and devices used) and accompanying short-term costs; however, the long-term economic impact of achieving the FPE has not been assessed. Methodology Data were obtained from a single-arm, prospective, multicenter study assessing the EMBOTRAP II device, ARISE-II (n=227). Patients who did not achieve complete revascularization were excluded. Among those who achieved complete revascularization (mTICI≥2c), the proportion of patients achieving each mRS score was assessed, stratified by the FPE status. Long-term costs per mRS score, obtained from a 2015 U.S. cost-effectiveness analysis that projected annual post-hospitalization inpatient/outpatient and nursing home costs using data from the National Death Index and Centers for Medicare and Medicaid Services (CMS), were applied to all patients. Post-hospitalization costs, in 2018 USD, were then compared between patients that did or did not achieve the FPE and incremental differences were calculated for a 1-year time horizon. Results In ARISE-II, 76% of patients (n=172) achieved complete revascularization; among these patients, 53% achieved the FPE. A significantly higher percentage of patients that achieved the FPE had good functional outcomes vs. those that did not achieve the FPE (80.5% vs. 61.0%, p=0.006). Estimated annual post-hospitalization costs were lower among patients that achieved FPE vs. those that did not achieve FPE, leading to estimated per-patient cost-savings of $3,876 (table 1). In the absence of cost data reported in ARISE-II, costs for healthcare resource use were obtained from the literature, which may not be generalizable across settings and is a limitation of this analysis. Additionally, the cost-effectiveness analysis used to inform the long-term costs per mRS score did not report costs for death (i.e., mRS 6), which had a lower incidence among patients who achieved the FPE vs. those who did not achieve the FPE (5.75% vs. 14.29%). Conclusion Among patients with final complete reperfusion (mTICI≥2c), achieving FPE may lead to long-term per-patient cost-savings of $3,876 in the first year due to improved functional outcomes. Disclosures O. Zaidat: 1; C; Cerenovus, Stryker, Medtronic, Penumbra, Genentech, Tesla Clinical Trial. 2; C; Cerenovus, Stryker, Medtronic, Penumbra. J. Saver: 2; C; Cerenovus, Stryker, Medtronic, Rapid Medical. H. Mattle: 1; C; Neuravi/Cerenovus. 2; C; Neuravi/Cerenovus. 3; C; Neuravi/Cerenovus. M. Ribo: 1; C; Stryker, Medtronic. 2; C; Cerenovus, Stryker, Medtronic, Anaconda Biomed. 4; C; Anaconda Biomed. A. Narata: None. A. Yoo: 1; C; Cerenovus, Stryker, Medtronic, Penumbra, Genentech. 2; C; Cerenovus, Genentech, Zoll Circulation. 4; C; Insera Therapeutics. H. Bozorgchami: 2; C; Cerenovus, Stryker, Coherex. C. Crivera: 4; C; Johnson & Johnson. 5; C; Johnson & Johnson. H. Cameron: 2; C; Employee of Cornerstone Research Group, contracted by Cerenovus. T. Andersson: 2; C; Cerenovus, Anaconda, Medtronic, Ablynx, Amnis Therapeutics, Rapid Medical.

Wide-necked bifurcation aneurysms (WNBAs) pose unique challenges for treatment via traditional endovascular approaches, due to the risk of coil herniation and the need to preserve patency in both parent and daughter vessels. The purpose of this study was to summarize published data associated with the occlusion of WNBAs via single and dual stent-assisted coil embolization. A systematic literature review was conducted using PubMed, Google Scholar, Ichushi, Cinii, and Medical Online databases. Studies were eligible for inclusion if they reported outcomes of interest for >10 patients between 1-Jan-2004 and 31-July-2018 in English or Japanese, and were not reviews, commentary, or case reports. At least 80% of the study population must have received endovascular treatment for unruptured or non-emergent WNBAs. Thirty-five publications (1,571 patients) were identified. Ten were non-randomized comparative studies while 25 were single-arm. Twenty utilized dual stent-assisted approaches (e.g., Y-stenting) and 15 utilized a single stent. Commonly reported outcomes included: complete/adequate occlusion, mortality, peri-procedural complications, technical success, recanalization, retreatment, and the modified Rankin Scale. No economic data or patient-reported outcome measures were described. With the exception of one study, assessment of clinical success was performed by the investigator rather than an independent core laboratory. Substantial variation was observed in occlusion rates for both single and dual stent-assisted treatment. For the single stent subgroup, complete occlusion ranged from 12.1-94.1% (immediate; n=9), 66.7-86.5% (6-12M; n=2), and 70.3-89.3% (12-24M; n=7). For the dual stent subgroup, complete occlusion ranged from 25.4-90.0% (immediate; n=10), 60.0-95.7% (6-12M; n=7), and 62.5-85.9% (12-24M; n=5). Retreatment and mortality were similarly reported with substantial variations. The evidence base for conventional endovascular treatments for WNBAs consists of low- to medium- quality studies with a limited scope of reported outcomes. As new therapies become available, conventional treatment approaches need to be better understood as an objective performance benchmark.