Soefje, Scott A

Background: Immunotherapy-based regimens have expanded the treatment landscape for unresectable hepatocellular carcinoma (uHCC); however, real-world data are limited. Methods: This retrospective, observational study used data from electronic medical records from Mayo Clinic sites across the United States. Patients with uHCC who initiated a first-line (1L) systemic therapy between June 2020–October 2022 with ≥2 follow-up visits were included. Treatment patterns, overall survival (OS), and post-index gastrointestinal (GI) bleeding were assessed by GI bleeding risk defined by Child–Pugh Class B or C, pre-index GI bleeding, uncontrolled hypertension, or significant varices and band ligation. Results: Of 186 included patients, 68.8% had GI bleeding risk and 31.2% did not. Atezolizumab plus bevacizumab was the most common 1L systemic therapy in patients with or without GI bleeding risk (72.7% and 29.3%, respectively). Median OS (95% confidence interval) with atezolizumab plus bevacizumab was 12.8 (8.0–19.3) months and not reached in patients with and without GI bleeding risk, respectively. OS rates with atezolizumab plus bevacizumab in patients with or without GI bleeding risk, respectively, were 52.3% and 70.6% at 12 months, 41.6% and 57.8% at 18 months, and 34.6% and 51.3% at 24 months. Post-index GI bleeding with atezolizumab plus bevacizumab occurred in 19.4% and 5.9% of patients with and without GI bleeding risk, respectively. Conclusions: During this study period, atezolizumab + bevacizumab was the most common 1L therapy for patients with uHCC, regardless of GI bleeding risk. OS rates with atezolizumab + bevacizumab were lower in patients with versus without GI bleeding risk. Findings highlight the unmet need for guidance on characteristics-driven treatment decisions.

Introduction Taxane medications, paclitaxel, and docetaxel, are chemotherapy agents that have a higher incidence of reported hypersensitivity and infusion reactions. To help classify these reactions, the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) is utilized. Prophylactic medications have been used to decrease the incidence and severity of these events. At our institution, medications that patients can receive prior to the initiation of a taxane infusion are a histamine 1 receptor antagonist (H1RA), histamine 2 receptor antagonist (H2RA), a steroid or a combination of these medications. The purpose of this retrospective review was to compare the rates and severity of infusion reactions based on the timing of prophylactic medication administration in the first and second doses of taxane infusions. Methods Patients who received paclitaxel or docetaxel from January 30 th , 2022, through January 30 th , 2023, were included in the analysis. To assist in the identification of a reaction, taxane administrations were flagged for review if a rescue medication was administered after the start of a paclitaxel or docetaxel infusion. The rates and severity of infusion reactions were analyzed based on the timing of prophylactic medication administration. A sub-group analysis comparing infusion reaction characteristics between taxanes given, was performed. Results Of the 1486 taxane infusions that were completed within the year, 249 infusion reactions were confirmed and graded utilizing the NCI CTCAE. When examining the first and second doses of a taxane (N = 536), we identified 222 infusions reactions. The odds of a patient having an infusion reaction, during the first and second doses, was found to be less likely for patients given a prophylactic medication 30 min prior to receiving a taxane compared to those who did not receive a pre-medication (p = 0.037). Conclusion This multisite retrospective study showed that administration of prophylactic medications 30 to 80 min prior to the first and second infusion of a taxane was the optimal timing to decrease the likelihood of patients having an infusion reaction. No difference in the severity of the reaction was seen. Most patients were able to complete the entire infusion, regardless of what rescue medications were used following the infusion reaction.

PURPOSE Teclistamab is initiated with a step-up dosing (SUD) schedule to mitigate the risk of cytokine release syndrome (CRS) and immune effector cell–associated neurotoxicity syndrome (ICANS). Early teclistamab users commonly received SUD in a hospital setting. This study aimed to evaluate safety and health care resource utilization (HRU) in real-world patients with multiple myeloma who initiated teclistamab SUD in an outpatient setting. METHODS This was a retrospective study using Mayo Clinic's electronic medical records from October 26, 2022, to October 31, 2023. Patient characteristics were summarized for all patients treated with teclistamab and separately for patients who started SUD outpatient. SUD pattern, safety, HRU, and post-SUD dosing schedule were described in patients with complete SUD. RESULTS At data cutoff, 65 patients received ≥1 teclistamab dose, including 58 patients who initiated SUD outpatient (median age, 69.2 years; male, 63.8%; White, 89.7%). Among 57 patients who completed SUD in an outpatient setting, all received premedications on the days of teclistamab administrations per label recommendation; 18 (31.6%) developed CRS (13 grade 1, four grade 2, and one grade 4) and two developed ICANS (one each with grade 2 and 4). All CRS and ICANS resolved with supportive care and all patients continued treatment. Eighteen patients were admitted to the hospital for CRS treatment, with a median CRS-related hospital stay of 2 days per admission. Most (60%) doses during SUD required <1 hour clinic time between administration and checkout. Post-SUD, clinic time for treatment doses decreased to <30 minutes for most doses (82%). CONCLUSION Outcomes of this study support outpatient administration as a safe and feasible option for teclistamab SUD to potentially reduce HRU and improve patient experiences.

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.

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: 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.