Oncology pharmacy practice in the United States: Results of a comprehensive, nationwide survey.

Introduction: This study was designed to describe the landscape of oncology pharmacy practice at patient facing institutional healthcare organizations throughout the United States. Methods: The Hematology/Oncology Pharmacy Association (HOPA) Practice Outcomes and Professional Benchmarking Committee conducted a multi-organization, voluntary survey of HOPA members between March 2021 and January 2022. Four overarching domains were targeted: institutional description, job function, staffing, and training/certification. Data were evaluated using descriptive statistics. Results: A total of 68 responses were analyzed including 59% and 41% who self-identified their organization as academic and community centers, respectively. The median number of infusion chairs and annual infusion visits were 49 (interquartile range (IQR): 32-92) and 23,500 (IQR: 8300-300,000), respectively. Pharmacy departments reported to a business leader, physician leader, and nursing leader 57%, 24%, and 10% of the time, respectively. The median oncology pharmacy full-time equivalents was 16 (IQR: 5-60). At academic centers, 50% (IQR: 26-60) of inpatient and 30% (IQR: 21-38) of ambulatory pharmacist FTEs were dedicated to clinical activities. At community centers, 45% (IQR: 26-65) of inpatient and 50% (IQR: 42-58) of ambulatory pharmacist FTEs were dedicated to clinical activities. As many as 18% and 65% of organizations required or encouraged certification for oncology pharmacists, respectively. The median number of Board-Certified Oncology Pharmacists was 4 (IQR: 2-15). Conclusion: As the number of patients with cancer rises, the oncology workforce must grow to support this expanding population. These results describe the practice landscape of oncology pharmacy at US healthcare institutions to serve as a foundation for future research evaluating metrics and benchmarks.

Oral Antineoplastics in Acute Myeloid Leukemia: A Comprehensive Review.

AML is a biologically and clinically heterogeneous disease that is associated with poor overall long-term survival. The expanding knowledge of genomic landscape in AML as well as advancements in molecular and chemical biology over the pathway in AML. After 40 years of stagnancy, the recent approval of numerous novel oral anti-leukemic agents for the treatment of AML has changed both the armamentarium of medications and treatment paradigms. These agents have unique clinical considerations in terms of administration, adverse effects, and monitoring parameters which may differ from clinician's historical expectations. Understanding the data, indication and clinical considerations for such novel oral anti-leukemic agents is paramount for clinicians caring patients with AML.

The Impact of a Hematopoietic Cellular Therapy Pharmacist on Clinical and Humanistic Outcomes: A RE-AIM Framework Analysis.

The hematopoietic cellular therapy (HCT) pharmacist is an essential member of the multidisciplinary care team. Yet, standardized incorporation of a pharmacist at transplantation centers remains challenging. Implementation science uses theory-driven and systematic approaches to integrate interventions into clinical practice. We describe our experience implementing an HCT pharmacist at our center and conducted a program evaluation using the Reach, Effectiveness, Adoption, Implementation and Maintenance (RE-AIM) framework. We implemented 1 full-time equivalent pharmacist to provide medication management services through a collaborative practice agreement (CPA) to the allogeneic transplantation population at a medium-sized center in rural Pennsylvania over a 2-year period. The HCT pharmacist documented all in-person and telephonic care encounters in the electronic medical record. A pharmacist intervention tool was developed to document identified medication-related problems with corresponding interventions and magnitude of intervention. Summary statistics including frequency and percentages were presented for categorical variables in RE-AIM domain. Over the 2-year period, the HCT pharmacist monitored 40 allogeneic patients at our institution accounting for 1531 patient encounters. The average duration of follow-up was 299 days. The HCT pharmacist medication therapy services were able to reach all allogeneic transplants at our institute. The HCT pharmacist managed 388 medications and identified 2156 medication related problems for which the pharmacist provided 2959 interventions. Time in therapeutic range of immunosuppression was 73.9% when managed by the HCT pharmacist through a CPA. Of the 24 patients and 9 caregivers who completed the patient satisfaction survey, 25 (76%) were strongly satisfied with their care. Pharmacy services were gradually adopted and expanded to incorporate additional populations, including 121 autologous transplant and 272 hematology patient encounters. The role of the HCT pharmacist was justified with hospital administration and sustained as a designated pharmacist role at our center. The implementation of an HCT pharmacist service can positively impact patient care. The RE-AIM framework provides a methodological approach for programmatic evaluation and generalizability. © 2022 American Society for Blood and Marrow Transplantation. Published by Elsevier Inc. All rights reserved.

Smaller but more frequent dosing of cefepime in the treatment of febrile neutropenia.

BACKGROUND: Generally national guidelines for febrile neutropenia recommend treatment with cefepime 2 g every 8 h. Due to beta-lactam's time dependent killing effects, it is hypothesized smaller doses given more frequently might be non-inferior. The objective of this study is to retrospectively evaluate the efficacy of cefepime 1 g every 6 h versus 2 g every 8 h in cancer patients with febrile neutropenia. METHODS: This retrospective, single-center, cohort study included patients with a diagnosis of febrile neutropenia treated with cefepime during an inpatient encounter. Patients were grouped based on receipt of cefepime 2 g every 8 h (high dose cohort) versus cefepime 1 g every 6 h (low dose cohort). The primary outcome compared the time to defervescence after cefepime initiation between the two dosing strategies. A subgroup analysis of the primary endpoint was conducted in patients who received both cefepime and vancomycin. RESULTS: Ninety-seven patients were included in the high dose cohort, and seventy-six patients were included in the low dose cohort. Baseline characteristics were similar between cohorts with the exception of race. The time to defervescence between the high dose cohort and low dose cohort were comparable between groups (49.2 vs. 46.7 h). The time to defervescence in subgroup analysis of patients who received empiric vancomycin and cefepime was 65.7 versus 59.7. CONCLUSION: Patients who received cefepime 1 g every 6 h were found to have similar trends in achieving time to defervescence compared to 2 g every 8 h.

Impact of a pharmacist-led telehealth oral chemotherapy clinic.

PURPOSE: Oral oncolytics come with significant concerns of noncompliance due to complex regimens, adverse effects, and high overall costs. The Geisinger Oral Chemotherapy Clinic is a fully telephone-based medication therapy disease management (MTDM) program designed to integrate pharmacists as advanced practitioners in hematology/oncology clinics for comanagement of oral chemotherapy. SUMMARY: To date, Geisinger has 11 oncology clinics and 3 full-time pharmacists designated to the management of oral chemotherapy. Pharmacists receive referrals for comanagement of patients starting oral oncolytics. Under a collaborative practice agreement, they can order laboratory tests as well as supportive care medications and refills. Pharmacists review planned therapies, perform medication reconciliations, and provide medication counseling. Once treatment has been initiated, pharmacists contact patients for laboratory and toxicity assessments. The clinic incorporates the use of customized smart data elements within the electronic medical record to collect data regarding pharmacist interventions and time allocations in the clinic. As of March 31, 2021, the clinic was actively following approximately 1,100 patients, resulting in an average of 80 to 90 encounters per day for new referrals, chemotherapy education, and laboratory and toxicity assessments. Approximately 2,113 patients were followed from December 1, 2019, to March 31, 2021, with 46,929 interventions documented. CONCLUSION: By obtaining provider buy-in for pharmacy services, acquiring enough personnel resources to meet the needs of the growing patient population and respective therapies, and proper utilization of technology, the program has thrived, allowing for increased provider and patient satisfaction. Future goals include expanding collection of pharmacist intervention metrics and analysis of patient perceptions of services provided by the clinic.

Cancer-Associated Venous Thromboembolism Treatment With Anti-Xa Versus Weight-Based Enoxaparin: A Retrospective Evaluation of Safety and Efficacy.

BACKGROUND: Venous thromboembolism (VTE) is a complication of cancer, for which low-molecular-weight heparin (LMWH) remains the preferred anticoagulant. Enoxaparin is traditionally dosed using weight. In certain populations, monitoring anti-Xa levels for therapeutic effect provides pharmacokinetic guidance for dose adjustments. There is a paucity of data regarding anti-Xa-directed enoxaparin dosing for treatment of VTE in patients with cancer. OBJECTIVE: This study aims to evaluate efficacy (recurrent VTE) and safety (major bleed) between enoxaparin anti-Xa-guided dose adjustments and weight-based dosing in patients with cancer-associated VTE. METHODS: This single-center, retrospective cohort study examined patients treated with enoxaparin for cancer-associated VTE using data from electronic health records. RESULTS: There were 674 patients who met the inclusion criteria, with 283 receiving anti-Xa-directed dose adjustments. Recurrent VTE, major bleed, or all-cause death occurred in 102 of 283 patients (36%) in the anti-Xa cohort and 166 of 391 patients (42.5%) in the weight-based cohort (hazard ratio [HR] = 0.73; 95% CI = 0.57-0.93; P = 0.01). When death was removed from the composite end point, there was no significant difference between the cohorts in recurrent VTE or major bleed (HR = 1.18; P = 0.38). In the anti-Xa cohort, a total of 1584 anti-Xa peak levels were collected, with 1324 (83.6%) drawn correctly in relation to enoxaparin administration. Of those, 714 (53.9%) were within therapeutic range. CONCLUSION AND RELEVANCE: Patients with cancer receiving anti-Xa-guided enoxaparin dose adjustments for initial VTE, compared with weight-based dosing, had no significant difference in the rate of recurrent VTE or major bleed.

Pharmacist value-added to neuro-oncology subspecialty clinics: A pilot study uncovers opportunities for best practices and optimal time utilization.

PURPOSE: To evaluate neuro-oncology clinician time utilization for medication management and identify a cost beneficial role for integration of a dedicated pharmacy specialists. METHODS: A pharmacist was temporarily integrated into a neuro-oncology clinic for a 30-day period to evaluate the clinical practice and perform a 14-day clinical chart evaluation and patient interactions as part of a single institutional exploratory analysis. The pharmacist completed screenings for drug-drug interactions, new therapies, medication reconciliation, and advanced interventions as part of a collaborative practice agreement for pharmacist autonomy. Pharmacist time spent was calculated and documented within the patient encounters to support physician decision-making. A comparative estimate of pharmacist versus physician time utilization and cost for each was completed to derive a savings analysis for integration of a dedicated clinic pharmacist. RESULT: During the 14-day clinical assessment, the pharmacist completed 147 encounters with 338 interventions. Of the encounters, 90% (n = 132) were higher complexity requiring plan modification, and approximately 48% (n = 162) of all interventions required ≥10 minutes of the pharmacist's time. Physician non-patient-facing time devoted to medication tasks was 5-hours weekly (0.125 FTE, full time equivalents), an estimated direct salary cost of $937/week ($45,000 yearly). Hire of a part-time pharmacist at 0.50 FTE would cover the clinical need with supported documentation and medication monitoring at a cost of $45,000/year. CONCLUSION: Defining the roles for dedicated neuro-oncology clinic pharmacists allows for cost-savings through re-allocation of physician time and improves subspecialty clinic operations as well as patient care.

Gilteritinib: A Novel FLT3 Inhibitor for Relapsed/Refractory Acute Myeloid Leukemia.

Acute myeloid leukemia (AML) is the most common adult leukemia, with an overall poor prognosis. New agents targeting various receptors may improve treatment outcomes and overall survival. FMS-like tyrosine kinase 3 (FLT3) is a targetable mutation occurring in one third of AML patients. It contributes to increased tumor proliferation and decreased cellular differentiation, ultimately conferring a poor overall prognosis. Among patients with FLT3-positive relapsed/refractory AML, outcomes are particularly dismal. Gilteritinib is a novel, second-generation FLT3 inhibitor approved by the U.S. Food & Drug Administration (FDA) for the treatment of relapsed/refractory AML with an FLT3 mutation as detected by an FDA-approved test.

Current advances in Hodgkin's lymphoma.

Hodgkin's lymphoma is a highly treatable malignancy. It has high cure rates yet there are many patients who relapse or are refractory to treatment. Traditionally, treatment has been with conventional chemotherapy; however, the development of brentuximab vedotin and immune checkpoint inhibitors has revolutionized the care of Hodgkin's lymphoma. This is a review of the current advances in the management of Hodgkin's lymphoma and a review of ongoing clinical trials in the field.

Clozapine drug-induced pancreatitis of intermediate latency of onset confirmed by de-challenge and re-challenge
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Definitive causality for medication-induced illnesses is difficult to determine, as often there are other causes for the condition. Additionally, for disease management there are often alternative treatment paths, and it is therefore clinically unnecessary to re-challenge with the suspected drug causing an adverse reaction; however, that was not the case in this clinical situation. Providers augmented treatment for this patient, but returned to the only therapy that controlled her condition, clozapine, as there appeared to be limited suitable alternatives. As outlined in this medical case, because the patient clinically responded only to clozapine, this forced providers to order multiple de-challenges and re-challenges resulting in confirmed drug-induced pancreatitis. Through courses of re-challenge, they were forced to find an effective dose and timing to maximize options for care using the drug despite inducing pancreatitis. At the time of this submission, providers had resumed a tolerated lower dose of clozapine without inducing pancreatitis. This case adds to the literature of drug-induced pancreatitis confirmation due to clozapine therapy being de-challenge and re-challenge.
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Randomized, Placebo-Controlled, Phase III Trial of Fosaprepitant, Ondansetron, Dexamethasone (FOND) Versus FOND Plus Olanzapine (FOND-O) for the Prevention of Chemotherapy-Induced Nausea and Vomiting in Patients with Hematologic Malignancies Receiving Highly Emetogenic Chemotherapy and Hematopoietic Cell Transplantation Regimens: The FOND-O Trial.

Evidence supports olanzapine for prophylaxis of chemotherapy-induced nausea/vomiting (CINV) for highly emetogenic chemotherapy; however, most studies focus on solid malignancies and single-day regimens. A randomized, double-blinded, placebo-controlled trial was conducted to compare the addition of olanzapine to triplet therapy (fosaprepitant, ondansetron, dexamethasone [FOND-O]) versus triplet therapy alone (FOND) in preventing CINV in hematology patients receiving single-day and multiple-day highly emetogenic chemotherapy and hematopoietic cell transplant (HCT) regimens (NCT02635984). The primary objective of this study was to compare complete response (CR; no emesis and minimal nausea, <25 mm on a 100-mm visual analog scale) during the overall assessment period (chemotherapy days plus 5 days after). Secondary objectives were the number of emesis, number of rescue medications, percent achieving minimal nausea, and percent achieving complete protection (CP; no emesis, rescue antiemetic, or significant nausea), all of which are reported as acute (chemotherapy days), delayed (5 days after chemotherapy), and overall phases. Olanzapine 10 mg or matching placebo were given on each chemotherapy day and 3 days after. Adults with hematologic malignancy receiving HCT regimens of melphalan, BEAM (carmustine, etoposide, cytarabine, melphalan), busulfan (Bu)/cyclophosphamide (Cy), Bu/fludarabine (Flu), Bu/melphalan, FluCy, FluCy-total body irradiation (TBI), etoposide-TBI, and ICE (ifosfamide, carboplatin, etoposide) or 7+3 chemotherapy regimens were included. An estimated 98 patients were required using alpha = .05 and 80% power. No significant differences existed in baseline characteristics between FOND-O (n = 51) and FOND (n = 50) arms. Mean duration of olanzapine was 7.7 days (range, 4 to 11). Discontinuation for possible adverse events occurred in 3 placebo and 0 olanzapine patients. CR was significantly higher for FOND-O in overall (55% versus 26%, P = .003) and delayed (60.8% versus 30%, P = .001) but not acute (P = .13) phases. Significantly more patients receiving FOND-O achieved no more than minimal nausea in overall (P = .001) and delayed phases (P = .0002), as well as fewer overall mean emesis counts (P = .005). CP rates were not different in any assessment phase (P ≥ .05 each). Within the HCT subgroup (n = 64), the CR, CP, and no significant nausea rates were significantly better for FONDO-O in overall and delayed phases (all P < .05). Analysis within the HCT subgroup revealed significant improvement in outcomes in delayed and overall phases with FOND-O in the autologous but not allogeneic cohort. Addition of olanzapine to an NK-1-based triplet antiemetic regimen significantly improved clinically relevant outcomes in the HCT population.

Olaratumab: A Novel Platelet-Derived Growth Factor Receptor α-Inhibitor for Advanced Soft Tissue Sarcoma.

OBJECTIVE: To review and summarize data on olaratumab, which was approved by the US Food and Drug Administration (FDA) in October 2016, in combination with doxorubicin, for the treatment of advanced soft tissue sarcoma. DATA SOURCES: A literature search using PubMed was conducted using the search terms olaratumab, IMC-3G3, and advanced soft tissue sarcoma from January 2005 to June 2017. STUDY SELECTION AND DATA EXTRACTION: The literature search was confined to human studies published in English. Trials of olaratumab for advanced soft tissue sarcomas were prioritized. DATA SYNTHESIS: Olaratumab is a human antiplatelet-derived growth factor receptor α monoclonal antibody. Its accelerated FDA approval was based on a phase II randomized trial of olaratumab plus doxorubicin (n = 66) versus doxorubicin monotherapy (n = 67) in patients with advanced soft tissue sarcoma. Olaratumab 15 mg/kg was administered intravenously (IV) on days 1 and 8 in combination with doxorubicin 75 mg/m2 IV on day 1 every 21 days for a total of 8 cycles compared to doxorubicin 75 mg/m2 IV monotherapy. The response rate was 18.2% with combination therapy versus 11.9% with monotherapy and median progression-free survival of 6.6 and 4.1 months, respectively. Additionally, overall survival was increased by 11.8 months in the olaratumab arm (26.5 months vs 14.7 months). Clinically relevant adverse effects in the olaratumab + doxorubicin arm included neutropenia (58%), mucositis (53%), nausea (73%), vomiting (45%), and diarrhea (34%). CONCLUSION: Olaratumab, in combination with doxorubicin, represents a novel treatment strategy for advanced soft tissue sarcoma and provides a significant survival advantage for this rare disease state with limited treatment options.

A Bioinformatics Practicum to Develop Student Understanding of Immunological Rejection of Protein Drugs.

Objectives. To design and implement a bioinformatics exercise that applies immunological principles to predicting rejection of protein drugs based upon patient genotype. Design. Doctor of pharmacy (PharmD) students used the Immune Epitope Database, a freely available bioinformatics tool. Over a 2-week laboratory, students interrogated whether a protein drug would be predicted to induce an immune response based upon patient genotype. Results were presented at the last laboratory session, and students completed reports discussing their findings. Assessment. Pre-lab quizzes and a final report were graded. Students answered questionnaires assessing perceived learning gains. To determine the impact on student understanding of immunity against protein drugs, the quality of student data analysis and comparisons to class data were graded. Independent measures of student learning demonstrated that students developed a greater understanding of how patient genotype could contribute to treatment failure with protein drugs. Conclusions. This study indicates that questions related to clinical immunology can be posed using bioinformatics tools.

Predicting Hemagglutinin MHC-II Ligand Analogues in Anti-TNFα Biologics: Implications for Immunogenicity of Pharmaceutical Proteins.

The purpose of this study was to evaluate the extent of overlapping immunogenic peptides between three pharmaceutical biologics and influenza viruses. Clinical studies have shown that subsets of patients with rheumatoid arthritis (RA) develop anti-drug antibodies towards anti-TNFα biologics. We postulate that common infectious pathogens, including influenza viruses, may sensitize RA patients toward recombinant proteins. We hypothesize that embedded within infliximab (IFX), adalimumab (ADA), and etanercept (ETN) are ligands of class II major histocompatibility complex (MHC-II) that mimic T cell epitopes derived from influenza hemagglutinin (HA). The rationale is that repeated administration of the biologics would reactivate HA-primed CD4 T cells, stimulating B cells to produce cross-reactive antibodies. Custom scripts were constructed using MATLAB to compare MHC-II ligands of HA and the biologics; all ligands were predicted using tools in Immune Epitope Database and Resources (IEDB). We analyzed three HLA-DR1 alleles (0101, 0401 and 1001) that are prominent in RA patients, and two alleles (0103 and 1502) that are not associated with RA. The results indicate that 0401 would present more analogues of HA ligands in the three anti-TNFα biologics compared to the other alleles. The approach led to identification of potential ligands in IFX and ADA that shares sequence homology with a known HA-specific CD4 T cell epitope. We also discovered a peptide in the complementarity-determining region 3 (CDR-3) of ADA that encompasses both a potential CD4 T cell epitope and a known B cell epitope in HA. The results may help generate new hypotheses for interrogating patient variability of immunogenicity of the anti-TNFα drugs. The approach would aid development of new recombinant biologics by identifying analogues of CD4 T cell epitopes of common pathogens at the preclinical stage.