Shah, Vishal

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]

Objective: To review the new indication of cyclin-dependent kinase (CDK4/6) inhibitor abemaciclib for the adjuvant treatment of hormone receptor positive (HR+), human epidermal growth factor receptor 2 negative (HER2−), axillary lymph node (LN) positive early breast cancer (EBC) at high risk of recurrence and a Ki-67 ≥20%. Data Sources: A literature search was performed through PubMed, ClinicalTrials.gov, and Food and Drug Administration (FDA) website (February 1, 2018, to December 23, 2021) to identify relevant information. Study Selection and Data Extraction: Human and animal studies related to pharmacology, pharmacokinetics, efficacy, and safety of abemaciclib were identified. Data Synthesis: Addition of abemaciclib to standard of care endocrine therapy (ET) for patients with high-risk clinicopathologic features and Ki-67 ≥20% demonstrated 30% reduction in the risk of developing invasive disease and distant recurrence. At 15.5 months, abemaciclib + ET demonstrated a significant improvement in invasive disease-free survival (IDFS) vs ET alone (hazard ratio [HR], 0.75; 95% confidence interval [CI], 0.60-0.93, P = 0.01). At 27 months, IDFS benefit was maintained (HR, 0.70; 95% CI, 0.59-0.82, P < 0.0001). Diarrhea occurred in more than 80% of patients in the abemaciclib arm. Relevance to Patient Care and Clinical Practice: This review describes the clinical applicability of adjuvant abemaciclib for patients with HR+, HER2− EBC at high risk for recurrence. Conclusion: Adjuvant abemaciclib significantly reduces the risk for early development of invasive disease and distant recurrence in patients with HR+, HER2− node positive EBC. Longer follow-up is needed to determine the impact of adjuvant abemaciclib on late disease recurrence and survival outcomes.

Abstract Purpose To decrease drug waste and cost by implementing automated chemotherapy dose rounding rules in the electronic health record (EHR). Dose rounding of chemotherapy is a recognized method for reducing drug waste, and professional organizations have published guidelines recommending dose rounding when possible. Summary On the basis of current literature and guideline recommendations, Mayo Clinic developed system-wide consensus to allow dose rounding for biologic and chemotherapy agents to the nearest vial size if rounding resulted in the dose being within 10% of the originally calculated dose or to a convenient measurable volume, based on concentration of the drug, if rounding to the nearest vial size resulted in the dose being outside the 10% range. Oncology pharmacists reviewed and analyzed all drugs listed in the EHR used in injectable form for the treatment of cancer and developed dose rounding rules. The rules were implemented and applied at the dose calculation stage before provider signature. From January to June 2019, approximately 40,000 cancer treatment doses were administered. The rounding rules saved a total of 9,814 vials of drug, of which 5,329 were for biologic agents and 4,485 were for oncolytic drugs. This resulted in a total 6-month cost savings of $7,284,796 (in 2019 dollars; biologics, $5,727,402; oncolytics, $1,557,394). Conclusion Systematic implementation of dose rounding rules utilizing the EHR can result in significant reduction of drug waste and realization of savings.

Abstract Introduction: Hematologic response (HR) particularly complete response (CR) is critical in patients (pts) with AL since it improves overall survival (OS) because of organ response (OrgR). Bor based therapies especially in combination with cyclophosphamide and dexamethasone (CyBorD) have shown to be an active regimen in AL. So far, there have been no comparative studies studying the effect of treatment with B-based regimens prior to SCT (Bor-SCT) versus SCT upfront or SCT preceded by non-Bor therapies (non-Bor-SCT). We present a retrospective analysis of data with an aim to compare the OS, OrgR and HR in the two cohorts. Methods: Charts were reviewed for the pts who underwent SCT for AL since 2004 until 2015 at Mayo Clinic in Arizona. HR and OrgR were determined using the consensus criteria from International Society of Amyloidosis.1 HR were noted at 3, 6 and 12 months from SCT. Results: Patients and disease characteristics: 63 pts were identified who underwent SCT for AL, of which 34 were in Bor-SCT and 29 were in the non-Bor-SCT cohort. Median age at diagnosis was 59.5 (range, 39 - 72) and 63 (range, 38 - 76) years and at SCT was 60 (range, 40 - 72) and 63 (range, 39 - 76) years for Bor-SCT and non-Bor-SCT, respectively. There were 13 (38%) females in Bor-SCT and 9 (31%) in non-Bor-SCT. Mean bone marrow involvement of plasma cells at diagnosis was 18% (SD±16.5) in Bor-SCT and 6.8% (SD±7.8) in non-Bor-SCT (p = 0.004). All pts had an ECOG performance score of better than 3 at the time of SCT. Fifteen (44%) pts had single organ involvement at diagnosis and 9 (26.5%) had 2-organ involvement in Bor-SCT. In non-Bor-SCT, 21 (72%) pts had single and 6 (21%) had 2-organ involvement (p = 0.04). More than 2 organs were involved in 10 (29%) pts in Bor-SCT and 2 (7%) in non-Bor-SCT. Heart was involved in 18 (53%) pts in Bor-SCT and 8 (28%) in non-Bor-SCT (p = 0.04) while kidney involvement was seen in 27 (79%) in Bor-SCT and 23 (79%) in non-Bor-SCT (p = 0.99). Median creatinine was not significantly different in the 2 groups at diagnosis or at the time of SCT. In Bor-SCT, no pts were on hemodialysis at the time of diagnosis or SCT. In non-Bor-SCT, 1 pt at diagnosis and 3 pts at SCT progressed to need hemodialysis. Lambda light chain was involved in 27 (82%) and 22 (76%) (p = 0.56) with a mean level of involved light chains being 59(SD±88.7) g/dL and 43.3 (SD±64.6) g/dL (p=0.4539) in Bor-SCT and non-Bor-SCT, respectively. Treatment: Thirty-one (91%) out of 34 pts in Bor-SCT group got treatment with CyBorD while 2 (6%) got Bor with dexamethasone and 1 (3%) got Bor with pegylated liposomal doxorubicin. In the non-Bor-SCT group, 20 (69%) out of 29 got no treatment, 4 (14%) got melphalan prednisone, 2 (7%) got dexamethasone alone, 1 (3%) got vincristine dexamethasone and 2 (7%) got lenalidomide dexamethasone prior to SCT. Transplant factors: Median time from diagnosis to SCT was 226.5 (range, 65 - 1108) days in Bor-SCT and 150.5 (48 - 1139) days in non-Bor-SCT (p=0.32). Full dose of melphalan (200 mg/m2) was used in 21 (62%) pts in Bor-SCT and 13 (34%) pts in non-Bor-SCT (p <0.001). Mean dose of cells used for SCT was 4.6 (SD±0.9) and 4.8 (SD±2.2) x 106/kg in Bor-SCT and non-Bor-SCT, respectively. Median time to neutrophil and platelet engraftment was 13 (range, 10 - 27) and 16 (range, 8 - 28) days in Bor-SCT while 11 (range, 7 - 16) and 13 (range, 10 - 25) days in non-Bor-SCT. Responses: HR at 3, 6 and 12 months from SCT and OrgR by the time of last follow up is described in table 1. Survival: Median OS was not reached in Bor-SCT as compared to 53.4 months in non-Bor-SCT (p =0.001), Figure 1. Conclusions: Our study suggests a benefit in HR, OrgR as well as OS by reduction of disease burden by Bor-based therapy prior to SCT. This benefit was observed despite a higher percentage of pts with cardiac involvement, more than 2 organ involvement and mean bone marrow plasma cells at diagnosis in Bor-SCT. Currently, it is not standard practice to use Bor-based therapy prior to SCT. A prospective study with larger number of pts would be required to confirm these findings. References: 1. Gertz MA et al. Definition of Organ Involvement and Treatment Response in Immunoglobulin Light Chain Amyloidosis (AL): A Consensus Opinion From the 10th International Symposium on Amyloid and Amyloidosis. Am J Hematol. 2005;79(4):319-328. Disclosures Dueck: Bayer: Honoraria. Mikhael:Abbvie, Celgene, Onyx, Sanofi: Research Funding. Bergsagel:Amgen, BMS, Novartis, Incyte: Consultancy; Novartis: Research Funding. Reeder:Novartis, Millennium, BMS and Celgene: Research Funding. Stewart:celgene: Consultancy. Fonseca:AMGEN: Consultancy; Janssen: Consultancy; Novartis: Consultancy; Sanofi: Consultancy; Bayer: Consultancy; Millennium, a Takeda Company: Consultancy; Millennium, a Takeda Company: Consultancy; AMGEN: Consultancy; BMS: Consultancy; Celgene: Consultancy; Patent: Patents & Royalties: Prognostication of MM based on genetic categorization of FISH of the disease; Patent: Patents & Royalties: Prognostication of MM based on genetic categorization of FISH of the disease; Patent Pending: Patents & Royalties: The use of calcium isotopes as biomarkers for bone metabolisms; AMGEN: Consultancy; AMGEN: Consultancy; Patent: Patents & Royalties: Prognostication of MM based on genetic categorization of FISH of the disease; Patent Pending: Patents & Royalties: The use of calcium isotopes as biomarkers for bone metabolisms; Millennium, a Takeda Company: Consultancy; Sanofi: Consultancy; Janssen: Consultancy; Millennium, a Takeda Company: Consultancy; Patent: Patents & Royalties: Prognostication of MM based on genetic categorization of FISH of the disease; Patent Pending: Patents & Royalties: The use of calcium isotopes as biomarkers for bone metabolisms; Patent Pending: Patents & Royalties: The use of calcium isotopes as biomarkers for bone metabolisms; Celgene: Consultancy; BMS: Consultancy; Bayer: Consultancy; Novartis: Consultancy.