Dose Intensity in Real-World Patients With Metastatic Renal Cell Carcinoma Taking Vascular Endothelial Growth Factor Receptor Tyrosine Kinase Inhibitors.

BACKGROUND: Tyrosine kinase inhibitors (TKIs) that target the vascular endothelial growth factor receptor (VEGFR) are oral therapies used to treat metastatic renal cell carcinoma (mRCC). VEGFR TKI treatment is often complicated by dose-limiting adverse events (AE). We sought to describe dose intensity and clinical outcomes in a real-world cohort of patients treated with VEGFR TKIs to better characterize dosing patterns and toxicity management compared with previously reported clinical trials. MATERIALS AND METHODS: We conducted a retrospective chart review of sequential patients with mRCC treated with VEGFR TKIs at 1 academic medical center from 2014 to 2021. RESULTS: 139 patients (75% male, 75% white, median age 63 years) were treated with 185 VEGFR TKIs in our real-world cohort. Per International Metastatic RCC Database Consortium criteria, 24% had good risk, 54% intermediate risk, and 22% poor risk mRCC. With their first VEGFR TKI, median relative dose intensity (RDI) was 79%. 52% of patients required a dose reduction, 11% discontinued treatment due to AEs, 15% visited the ED, and 13% were hospitalized for treatment-related adverse events. Cabozantinib had the highest rate of dose reductions (72%) but a low rate of discontinuation (7%). Real-world patients consistently had lower RDI than reported clinical trials with more frequent dose reductions, fewer drug discontinuations, shorter progression-free survival, and shorter overall survival. CONCLUSION: Real-world patients were less able to tolerate VEGFR TKIs compared to patients treated on clinical trials. Low real-world RDI, high dose reductions, and low overall discontinuation rates can inform patient counseling prior to treatment initiation and during therapy.

Outpatient initiation of venetoclax in patients with acute myeloid leukemia.

INTRODUCTION: Venetoclax is a treatment option in patients with acute myeloid leukemia (AML) in both the front-line and relapsed/refractory settings. Initiation of therapy has been previously restricted to the inpatient setting at some institutions due to a risk of tumor lysis syndrome (TLS) and limitations in medication access efficiency given the high cost of therapy. METHODS: We assessed the safety of initiating venetoclax in the outpatient setting through a single-arm, retrospective study of adult AML patients between April 1, 2019 and June 30, 2020. RESULTS: Eighty-two patients started venetoclax during this time, with 47 (57%) patients initiated in the outpatient setting. Fifty-five percent of patients received venetoclax as first-line treatment for AML (n = 45) and 45% of patients received venetoclax for relapsed/refractory AML (n = 37). Successful initiation, defined as no hospitalizations secondary to TLS within seven days of therapy initiation, occurred in 98% of patients. The rate of TLS was 2.1% (n = 1) following venetoclax initiation. TLS symptoms were managed during hospitalization, requiring only one day of missed AML therapy. Median turnaround time for medication access was three days. Hospitalizations within seven days occurred in 17% of patients (n = 8), with the majority due to febrile neutropenia. CONCLUSIONS: The results of our study provide further evidence for the safety and feasibility of initiating venetoclax in the outpatient setting with a pharmacist-led interdisciplinary protocol.

Levofloxacin for Antibacterial Prophylaxis in Pediatric Patients With Acute Myeloid Leukemia or Undergoing Hematopoietic Stem Cell Transplantation.

OBJECTIVE: This study aimed to evaluate the use of levofloxacin for the prevention of bacterial infections in pediatric patients with acute myeloid leukemia or those undergoing hematopoietic stem cell transplantation. METHODS: This study was a single-center, retrospective review designed to assess the frequency of bacteremia with levofloxacin prophylaxis compared with historical controls that used other, clinician-directed antibacterial prophylaxis. The primary outcome of the study was microbiologically documented bacteremia. Secondary outcomes included febrile neutropenia, clinically documented infection, duration of neutropenia, treatment antibiotic exposure days, Clostridioides difficile infection, and infection-related mortality. RESULTS: Of the 60 patients included, 24 patients with 32 hospital admissions received levofloxacin and 36 patients with 48 hospital admissions received clinician-directed prophylaxis. There was no difference found in the frequency of bacteremia between levofloxacin and clinician-directed prophylaxis (15.6% vs 10.4%, p = 0.49). There was no difference in the incidence of febrile neutropenia, clinically documented infection, treatment antibiotic exposure days, or 30-day infection-related mortality between the 2 groups. The levofloxacin group had a longer mean duration of neutropenia compared with clinician-directed prophylaxis (26.8 days vs 16.4 days, p = 0.01). CONCLUSIONS: There was no difference in bacteremia between levofloxacin prophylaxis and clinician-directed prophylaxis in pediatric patients with acute myeloid leukemia or those undergoing hematopoietic stem cell transplantation. Levofloxacin prophylaxis is an appropriate alternative for the prevention of serious bacterial infections in this patient population, although further studies are needed to confirm these results.

Pharmacists' Role in Managing Patients with Chronic Lymphocytic Leukemia.

Chronic lymphocytic leukemia (CLL) is a hematologic malignancy that has seen significant advances in care over the last 5 years with the approval of oral agents such as ibrutinib and venetoclax for the treatment of this disease. As such, there has been a substantial shift away from the traditional chemotherapy infusions which have allowed patients greater autonomy with oral cancer therapies. This paradigm shift poses new challenges for the medical team, including drug-drug interactions, adherence counseling, and financial toxicity. Pharmacists are uniquely trained and equipped to help to manage the changing landscape of CLL care. From identifying common medications which may impair ibrutinib clearance to ensuring patients are on the appropriate anti-infective prophylaxis while receiving obinutuzumab, pharmacists can play a vital role in ensuring the highest quality of patient care. Furthermore, additional credentialing of clinical pharmacists in select states allows for independent visits with the pharmacists, allowing for greater involvement, particularly for initiation of venetoclax and management of ibrutinib-induced toxicities. Pharmacists are essential to both expanding and enhancing the care of patients with CLL and should be leveraged to improve patient outcomes whenever possible.

Effectiveness of oral antibiotics for definitive therapy of non-Staphylococcal Gram-positive bacterial bloodstream infections.

BACKGROUND: Data on the effectiveness of definitive oral (PO) antibiotics for BSIs in preparation for discharge from hospital are lacking, particularly for Gram-positive bacterial BSIs (GP-BSI). The objective of this study was to determine rates of treatment failure based on bioavailability of PO antimicrobial agents used for GP-BSI. METHODS: This was a single-center, retrospective cohort study of adult inpatients admitted to an academic medical center over a three-year period. Patients with a non-staphylococcal GP-BSI who received intravenous antibiotics and were then switched to PO antibiotics for at least a third of their treatment course were included. The cohort was stratified into high (⩾90%) and low (<90%) bioavailability groups. The primary endpoint was the proportion of patients experiencing clinical failure in each group. Secondary endpoints included clinical failure stratified by antibiotic group, bactericidal versus bacteriostatic PO agents, and organism. RESULTS: A total of 103 patients met criteria for inclusion, which failed to reach the a priori power calculation. Of the patients included, 26 received high bioavailability agents and 77 received low bioavailability agents. Infections originated largely from a pulmonary source (30%) and were caused primarily by streptococcal species (75%). Treatment failure rates were 19.2% in the high bioavailability group and 23.4% in the low bioavailability group (p = 0.66). Clinical failure stratified by subgroups also did not yield statistically significant differences. CONCLUSIONS: Clinical failure rates were similar among patients definitively treated with high or low bioavailability agents for GP-BSI, though the study was underpowered to detect such a difference.

Exploring the Consequences on Memory of Students Who Know They Have Access to Recorded Lectures.

Objective. To elucidate how students' knowledge of future access to recorded lectures impacts their ability to immediately recall, to delay recall, and to restudy information. Methods. Seventy-eight participants were randomly divided into two groups: knowledge of future access to recorded lectures after class and knowledge of no future access to recorded lectures after class. Participants viewed two mini lectures (10-12 minutes each) in a simulated classroom. Participants were told whether they would or would not be able to restudy lectures through future access to the recorded lectures just prior to their test one week later. Participants were tested immediately following the lectures and after a one-week delay. Prior to the delayed test, participants restudied one of the two lectures. The primary outcome was the participants' performance on the lecture material following immediate testing. Secondary outcomes included performance on delayed tests, performance after restudying the lectures and note-taking behavior. Results. Having access to a recorded lecture did not influence immediate recall. One week after the simulated class, reviewing videos did improve performance (d∼.70). Participants with knowledge of no future access forgot less information (d=.42) over time compared to the group that knew they had future access (d=.53); even though this latter group wrote longer notes. Conclusion. These findings suggest that there is no mnemonic-benefit to having knowledge of access to recorded classes. Reviewing recorded lectures did improve scores on an immediate test. However, participants with knowledge they had access to the recorded lectures to restudy them had larger effect sizes for loss of material.

Recorded Lectures as a Source of Cognitive Off-loading.

Objective. To assess and elucidate the impact of student pharmacists' knowledge of future access to recorded lectures on their ability to remember information presented during lecture. Methods. Pharmacy students viewed 50 minutes of videotaped lecture in a simulated class period. For the early lecture material, participants were instructed as to whether or not they would have future access to the recorded lectures for restudy prior to their test one week later. For the late lecture material, participants were instructed they would not have future access to lecture material. Participants were tested immediately following the lectures and again one week later. The primary outcome was the participants' performance on the examination administered immediately following presentation of the late lecture material. If participants had preserved cognitive resources (eg, memory, attention) because of knowledge they would have future access to recorded lectures, performance was expected to be higher on the late lecture material. Results. Overall performance on the examinations did not differ between participants who knew they would have access to the lecture material for later restudy and those who did not. There was, however, loss of knowledge over time. Participants with knowledge of future access to recorded lectures wrote more notes, which correlated with better performance on the examination. Conclusion. These findings suggest knowledge of future access to recorded lectures did not enhance the ability of participants to remember other information and therefore, may not free-up cognitive resources that could be used for other tasks within the classroom.