Soefje, Scott A.

PURPOSE Globally, cancer drug expenditure exceeds $185 in US dollars (USD) billion, with the United States contributing $75 (USD) billion. Many cancer drug doses are calculated on the basis of body weight or body surface area, which often results in leftover drug in partially used single-dose vials (SDVs). The cost of wasted drug is a huge financial burden on the US health care system. We evaluated the cost savings resulting from the reduction of SDV wastage, achieved through the implementation of automated dose rounding rules in electronic health records (EHRs). METHODS Mayo Clinic implemented automated dose rounding rules within the EHR. These rules were designed to round calculated doses to the nearest SDV if the vial size closely matched the original calculated dose, within a 10% threshold. We assessed doses administered between January 2019 and December 2021, and computed cost-savings, waste reduction, and cost of waste for chemotherapy drugs. RESULTS In 3 years, 36.1% of doses were rounded down, 35.8% were rounded up, and 28.1% were exact doses. By rounding doses down to a vial size, we achieved cost-savings of $39.75 (USD) million and prevented 62,065 SDV of cancer drugs from going to waste. By rounding doses up, we avoided wasting $9.95 (USD) million worth of drugs. However, there were still instances where the rounding fell outside of the 10%, resulting in wasted drugs worth $25 (USD) million. CONCLUSION The substantial burden imposed on patients and the US health care system because of cancer drug wastage is of significant concern. Although the automated dose rounding system represents a partial solution for this issue, a comprehensive approach involves the imperative development of policy and legislative solutions to effectively mitigate the challenges associated with cancer drug waste.

11176 Background: Progression-free survival (PFS) is frequently measured in oncology clinical trials. In analyses outside of the trial setting, various strategies have been utilized to assess real-world PFS (rwPFS), including manual abstraction of clinical records, natural language processing (NLP) of oncology notes and radiology reports, and longitudinal analyses of radiologic images. Here we develop and validate a new semi-automated workflow that combines NLP of clinical notes with structured electronic health record data to facilitate the evaluation of rwPFS in patients with metastatic breast cancer (mBC). Methods: This study analyzes de-identified EHR data using nference nSights. The data is extracted following privacy-preserving protocols and is HIPAA compliant. The overall cohort included 316 patients with HR-positive, HER2-negative mBC who initiated Palbociclib and Letrozole combination therapy between January 1, 2015 and December 31, 2021. We developed and implemented an ensemble of deep-learning NLP frameworks to capture progression events from unstructured clinical notes and radiology reports. A change in the line of therapy, as determined by structured drug order/administration records, was also considered a progression event. We used manually curated “ground-truth” datasets to evaluate the performance of the progression-event capture workflow at the levels of both sentences (N = 1000) and patients (N = 100) by calculating sensitivity, specificity, precision, accuracy, and F1 scores. Progression events and censoring events (death, loss to follow-up, end of study period) were considered to compute rwPFS. Results: At the sentence level, progression events were captured from clinical notes and radiology reports with a sensitivity of 99.8%, specificity of 96.7%, and accuracy of 98.2% (Table). At the patient level, initial progression was correctly captured within a window of +/-30 days with a sensitivity of 92.5%, specificity of 83.0%, and accuracy of 88.0% (Table). In a sample of 100 patients, the median rwPFS was determined to be 25 months (95% CI; 15-35 months) by manual curation and 22 months (95% CI; 15-35 months) by the semi-automated workflow. In the overall cohort, median rwPFS was 20 months (95% CI; 18-25 months). Conclusions: An ensemble of NLP algorithms extracted progression events from clinical notes and radiology reports with high accuracy. A semi-automated workflow enabled rapid and accurate determination of rwPFS in mBC patients receiving a combination chemotherapy regimen. Further evaluation of this workflow to estimate rwPFS in other cancers and therapeutic settings is warranted. [Table: see text]

PURPOSE Daratumumab is an anti-CD38 monoclonal antibody used to treat multiple myeloma and light chain amyloidosis. Because daratumumab may cause reactions after intravenous or subcutaneous (SC) administration, the manufacturer labeling recommends administration of premedications before every dose. Given incidence of infusion reactions appears to be rare after cycle 1, in April 2022, the Mayo Clinic implemented a practice change in which premedications were omitted from all daratumumab order sets after completion of cycle 1. This study investigated the safety of this practice. METHODS A retrospective chart review at the Mayo Clinic reviewed eligible patients with multiple myeloma or amyloid light-chain (AL) amyloidosis who received their first dose of daratumumab within the 4 months preceding the date of implementation (preimplementation group) or no more than 4 months after (postimplementation group) the date of implementation on April 13, 2022. Data were collected only from the first eight once per week doses of daratumumab. The primary outcome was the incidence of infusion-related reactions. Data analyzed used descriptive statistics. RESULTS Nearly all patients (95.9%) received daratumumab by SC route of administration. Of the 97 patients in the preimplementation group, >90% received premedications throughout cycles 1 and 2, and five patients (5.2%) experienced infusion reactions. Of 72 patients in the postimplementation group, <20% received premedications during cycle 2 and three patients (4.2%) experienced infusion reactions. All infusion reactions occurred within the first daratumumab cycle, indicating elimination of cycle 2 premedications did not cause any infusion reactions. No patient experienced more than one infusion reaction. CONCLUSION Omission of premedications after cycle 1 of daratumumab did not increase the incidence of infusion. Premedications may safely be omitted after cycle 1 of daratumumab when administered by the SC route.

Background Teclistamab, the first-in-class B-cell maturation antigen (BCMA) x CD3 bispecific therapy was recently approved by the FDA for the treatment of triple-class exposed relapsed or refractory multiple myeloma (MM) after ≥ 4 prior lines of therapy. Because of the risk of cytokine release syndrome (CRS) and immune effector cell-associated neurotoxicity syndrome (ICANS), the step-up dosing (SUD) of teclistamab is commonly administered in an inpatient setting among early users. Mayo Clinic has a well-established hospital-based outpatient program for novel immunotherapies. Since the FDA approval, teclistamab SUD has been administered as part of this program. Each dose of the SUD is administered in an outpatient setting, and the patient is given a remote monitoring kit to regularly measure vital signs and stay connected with the command center for signs and symptoms of CRS and ICANS throughout the entire SUD period. This study aimed to evaluate early safety outcomes and healthcare resource utilization during SUD in real-world (RW) patients who initiated teclistamab under the outpatient administration model across 3 Mayo Clinic locations (Rochester, MN, Phoenix/Scottsdale, AZ, Jacksonville, FL). Methods This was a retrospective study using Mayo Clinic's electronic medical records from October 26, 2022 to June 12, 2023. Eligible patients were adults diagnosed with MM who had initiated commercial teclistamab at any of the 3 Mayo Clinic locations. Patient characteristics, rates and severity of CRS and ICANS, as well as healthcare resource utilization during SUD were described. Time between teclistamab administration and patient check-out was reported for SUD and treatment doses, respectively. Results At the time of data cutoff, 39 patients received at least 1 teclistamab dose across the 3 locations (median age 67.2 years; male: 74%; White: 87%; non-Hispanic: 92%), including 36 patients who initiated teclistamab SUD directly in an outpatient setting. A total of 8 (21%) patients had MM with high-risk cytogenetics and 14 (36%) had prior exposure to other BCMA-targeted therapies. Prevalent comorbidities prior to receiving teclistamab included anemia (77%), hypertension (56%), lytic bone lesions (51%), neutropenia (49%), and hypogammaglobulinemia (41%). Renal impairment or failure was observed in 31% of the patients (Table 1). Almost all patients received acetaminophen (95%), diphenhydramine (95%), and dexamethasone (92%) as pre-medications on the same day as teclistamab administrations during SUD. Of the teclistamab doses with clinic time data, the majority (62%) of doses during SUD required 30 minutes to 1 hour of clinic time for monitoring between administration and check-out. After SUD, the clinic time for weekly treatment doses decreased to less than 30 minutes for most (79%) doses (Figure 1). In patients who completed SUD by data cutoff (n = 37), most patients (70%) received the SUD on a 3-day dose interval (i.e., day 1, 4, 7). The mean time between the first and third doses was 6.3 days. Among the 37 patients with complete SUD, 12 (32%) developed CRS. The highest CRS grade was grade 1 for 10 patients; 1 patient had a grade 2 CRS, and 1 patient had a grade 4 CRS. The patient with grade 4 CRS concurrently decompensated during a dialysis session and all symptoms were considered for CRS grading. A total of 6 patients had recurrent CRS, including 1 patient with 3 events during SUD. All patients who developed CRS during SUD (n=12) were admitted to the hospital for treatment, with a total of 19 admissions across all patients and a median length of stay of 1.7 days per admission. Among patients who were admitted for CRS (n=12), the majority were treated with acetaminophen (92%), diphenhydramine (83%) and dexamethasone (83%); tocilizumab was given to the 2 patients with CRS grade 2 or higher. Only 1 ICANS event (grade 2) was observed in 1 patient during SUD, after dose 3, and the patient was admitted to the hospital for treatment. Conclusion This study evaluated early RW safety outcomes of teclistamab under an outpatient administration model and found the CRS rate and severity to be comparable with other RW evidence generated from various data sources. Outcomes related to teclistamab SUD from Mayo Clinic supported the safety and feasibility of outpatient administration model as a potential option to reduce healthcare resource utilization and improve treatment experiences.

68 Background: While immune checkpoint inhibitors (ICIs) have revolutionized cancer treatment, their high cost and limited global supply pose major challenges. Optimizing ICI dosing to achieve a minimum effective dose that has shown to maintain clinical benefit may be a potential solution with significant savings to the health system. We investigated potential savings in Medicare that could be attained from alternative ICI dosing. Methods: We conducted a literature review including original Phase 1/2 trials describing the minimal effective dose of three commonly used ICIs: Pembrolizumab (P), Nivolumab (N) and Atezolizumab (A). Alternate dosing strategies based on existing data for Pembrolizumab (2 mg/kg), Nivolumab (1 mg/kg) and Atezolizumab (4 mg/kg) were proposed. Publicly available CMS data on Medicare Part B expenditure for these therapies was utilized to obtain average cost per dosage unit, mg/dosage unit, and number of Medicare beneficiaries between 2018-2021. Average cost per dose and total cost per ICI was calculated based on current FDA approved dosing and alternate dosing strategies. Results: The average wholesale cost per fixed dose for P (200 mg), N (480 mg), and A were $9,242.00, $12,460.80, and $8,616.00, respectively. Implementing the proposed alternate dosing strategies led to a substantial reduction in drug costs: P ($7,393.60), N ($2,076.80), and A ($2,297.60). The ensuing cost savings were calculated based on the annual number of Medicare beneficiaries. From 2018-2021, the average total savings were estimated to be $95,545,182 for Pembrolizumab, $294,734,264 for Nivolumab, and $62,937,582 for Atezolizumab (Table). The cumulative average total cost savings from 2018-2021 exceeded $453 million. Conclusions: We demonstrate potential savings in Medicare with implementation of an alternative ICI dosing strategy. Our study underscores an urgent need to better understand clinical efficacy and cost savings from a patient perspective, and feasibility from a regulatory standpoint. This perspective may hold considerable global implications, providing a roadmap for cost-effective care in the domain of immunotherapy. [Table: see text]

Background: Pharmacist order verification is a critical step in ensuring medication safety for patients. While the second pharmacist verification (SPV) before dispensing anticancer therapies has been a longstanding practice, its continued necessity in the context of modern electronic health systems lacks robust evidence. Objective: This study aimed to assess the frequency of interventions performed by a second pharmacist to determine the ongoing effectiveness of the SPV process. Methods: This retrospective chart review was conducted at the Mayo Clinic, encompassing all anticancer therapy orders that necessitated an SPV. The study period extended from January 1, 2019, to June 30, 2021, and included inpatient and outpatient anticancer orders. The quantification and reporting of alterations made to discrete order fields subsequent to initial pharmacist verification of clinical significance were performed, utilizing the total number of anticancer therapy orders as the denominator. Results: Approximately 300 000 anticancer therapy orders were screened for inclusion criteria and 2.6% (N = 7634) of orders were modified on the SPV. Most changes were in the categories of rate (N = 1962), order start time (N = 1219), and pharmacy communication note (N = 777). Dosing changes greater than 10% accounted for 0.03% (N = 99) of the orders, with 10 anticancer therapies responsible for more than 50% of these changes. Conclusion and relevance: This study represents the largest report on the impact of SPV in a modern era. Our results suggest the SPV may be valuable for a small proportion of chemotherapy orders but raises questions about the necessity for broad application of this practice.

Introduction Prioritization and acuity tools have been leveraged to facilitate targeted and efficient clinical pharmacist interventions. However, there is a lack of established pharmacy-specific acuity factors in the ambulatory hematology/oncology setting. Therefore, National Comprehensive Cancer Network's Pharmacy Directors Forum conducted a survey to establish consensus on acuity factors associated with hematology/oncology patients that are high priority for ambulatory clinical pharmacist review. Methods A three-round electronic Delphi survey was conducted. During the first round, respondents were asked an open-ended question to suggest acuity factors based on their expert opinion. Respondents were then asked in the second round to agree or disagree with the compiled acuity factors, in which those with ≥75% agreement were included in the third round. The final consensus was defined as a mean score ≥3.33 on a modified 4-point Likert scale (4 = strongly agree, 1 = strongly disagree) during the third round. Results A total of 124 hematology/oncology clinical pharmacists completed the first round of the Delphi survey (invitation response rate, 36.7%), of which 103 completed the second round (response rate, 83.1%) and 84 the third round (response rate, 67.7%). A final consensus was achieved for 18 acuity factors. Acuity factors were identified in the following themes: antineoplastic regimen characteristics, drug interactions, organ dysfunction, pharmacogenomics, recent discharge, laboratory parameters, and treatment-related toxicities. Conclusions This Delphi panel of 124 clinical pharmacists achieved consensus on 18 acuity factors that would identify a hematology/oncology patient as a high priority for ambulatory clinical pharmacist review. The research team envisions incorporating these acuity factors into a pharmacy-specific electronic scoring tool.

Background: Many health care organizations offer pediatric infusions in outpatient infusion centers or, as in our organization, in a hospital-based outpatient Pediatric Infusion Therapy Center (PITC). When restrictions related to the COVID-19 pandemic decreased our PITC appointment capacity by 40%, other patient and family satisfaction issues were exacerbated. We implemented a new approach to pediatric infusions with the aim of improving patient and family satisfaction and reducing the amount of time in an appointment itinerary without negatively affecting patient safety. Methods: Our team used a phased approach to pilot the administration of short chemotherapy infusions in the same outpatient clinic examination rooms where consultation and routine office visits were conducted. Patients saw their specialist for an examination and, if clinically indicated, their infusion was administered in the same room. Appointment itineraries were then completed. The team tracked efficiency, satisfaction, and safety metrics related to the new process. Results: All efficiency metrics improved. No harm came to the 49 unique patients who received a total of 184 infusions. Patient appointment itineraries were shortened by an average of 1.03 hr. Satisfaction survey responses indicated a clear preference (93%) for the new process. Discussion: The novel approach of offering short infusions in outpatient clinic examination rooms provides an opportunity to ease capacity constraints and further increase patient and family satisfaction. This method may be especially helpful for health care organizations when external influences (e.g., lack of physical space, challenging patient volumes, and pandemics) necessitate a change.

PURPOSE: Median duration of daratumumab (DARA) administration for treatment of multiple myeloma is 3-7 hours for the intravenous formulation (DARA IV) and 3-5 minutes for the subcutaneous formulation (DARA SC). Here, we describe clinical administration characteristics of DARA using a novel method for data extraction from electronic health records. METHODS: Time-based measurements were extracted using a scheduling/pharmacy software program that tracked patient movement through appointments for patients initiating DARA in Mayo Clinic infusion centers from April 5, 2017, to October 14, 2021. Cohorts included patients who received DARA IV or DARA SC, or converted from DARA IV to DARA SC. The DARA SC cohort was further analyzed before (DARA SC initial) and after (DARA SC shortened) a reduction in the postadministration observation time mandated by the treatment plan. Events associated with administration-related reactions (ARRs) were also identified. RESULTS: Median total clinic times were 2.7-3.0 hours shorter for DARA SC versus DARA IV. Median clinic times were highest at dose 1 and decreased with subsequent doses. Median total chair times were 2.7-2.8 hours shorter for DARA SC versus DARA IV. Incidences of ARR-related events with DARA SC were low across doses. CONCLUSION: Reduced clinic times were observed with DARA SC, indicating that use of DARA SC as a treatment option results in time savings that may free clinic resources. Furthermore, novel methods of electronic health record data extraction can provide insights that may help inform clinic resource optimization.

8 Background: At Mayo Clinic, the implementation of an automated chemotherapy dose rounding program has resulted in significant cost savings when doses are rounded down to a vial size, however, the cost burden from drug waste continues to be a significant issue when rounding to a vial size is not within our 10% rounding allowance. The mismatch between drug doses and the marketed vial sizes, along with the limitations to the use of single dose vials is a recognized problem, resulting in billions of dollars of wasted drugs in the United States.The goal of our study was to quantify the cost of the wasted amount of chemotherapy and biologic drugs after the implementation of an automated dose rounding program. Methods: Using the electronic health record (EHR), data was collected for biologic and oncolytic agents administered from 1/1/2019 through 12/31/2021. Drugs with waste documented during preparation and that were administered to cancer patients were selected for analysis. The % of doses with waste documented was calculated based upon the total number of all doses given. The total cost of the drug administered along with the cost of the amount of drug wasted were calculated based upon costs listed in the EHR at the time of administration. Results: For the 3-year period, 446,832 doses were dispensed with 47,626 (10.7%) of those doses having waste documented. The total cost of the drugs with documented waste was $114,323,203 with 21.9% ($25,086,608) accounting sole for wasted drug. Five drugs accounted for 59% of the total cost of the drug waste (Table). When examining individual drugs with a high % of doses with documented waste, methoxsalen, epirubicin, eribulin, topotecan, & bortezomib each had > 70% of doses with a documented wasted amount. Conclusions: Despite having an aggressive institutional dose rounding policy, drug waste still results in considerable and significant costs to the Mayo Clinic System. Our data likely underestimates the total cost of drugs waste given that waste documentation requires manual entry into the EHR at the time of preparation. Our results support the need to create and develop solutions that could lead to reduced waste costs which include re-examining the weight based dosing of drugs, mandating pharmaceutical companies to have vial sizes that more appropriately meet the range of standard dosing, developing more multi-dose vials that can be shared across multiple patients, utilizing closed-system transfer devices to extend beyond-use-dating time, or requiring pharmaceutical companies to reimburse payers and patients for the cost of the amount wasted. Drug waste is still a considerable issue and one that needs to be addressed at a policy level.[Table: see text]