HOPA 12th Annual Meeting Poster Award Winners
Morgan Belling, PharmD
Lisa M. Cordes, PharmD BCOP BCACP
Oncology Clinical Pharmacy Specialist
National Institutes of Health
Featured in this article are excerpts from Dr. Burke’s and Dr. Folan’s research posters. Their posters, as well as those submitted by other residents and students, may be found on the HOPA website by selecting the “Education and Conference” tab, then “Conference Archives.” Please note that access to these electronic posters is limited to registered attendees of the HOPA Annual Conference.
The HOPA Annual Conference consistently offers educational sessions to encourage sharing information and ideas among attendees, and the 12th Annual Meeting was in keeping with this tradition. One of the best opportunities for students, residents, and practitioners to disseminate and discuss research is through the poster presentation sessions. The research projects presented at the annual conference are assessed by a committee of HOPA members, and particularly impactful projects are recognized with awards in the categories of clinical/translational research or practice management. This year’s award winners were Dr. Ellen Burke, PGY-2 oncology pharmacy resident at the University of Kansas Hospital (UKH), and Dr. Stephanie Folan, PGY-2 oncology pharmacy resident at the University of Texas MD Anderson Cancer Center.
Dr. Burke was recognized for her research in the area of practice management focusing on “Assessment of Cetuximab- Induced Infusion Reactions and Administration Re-Challenge at an Academic Medical Center.” Although cetuximab is typically well-tolerated, the U.S. Food and Drug Administration-approved labeling includes a black-box warning for serious infusion reactions (IR). Clinical trials have reported a 15%–20% incidence for all grades of IR, and a 3%–5% incidence for grade 3/4. Retrospective studies have demonstrated a higher incidence of all grade IR and grade 3/4 IR in areas of the southeastern United States as well as Kansas and Missouri. Limited data are available regarding cetuximab rechallenge after an initial IR, and patients who experience an IR may be excluded from potentially beneficial therapy with cetuximab if the medication is discontinued. Patients at UKH are rechallenged on the same day as an initial IR using a slower infusion rate and administering additional premedications to help prevent an IR secondary to the rechallenge dose.
The primary objective of Dr. Burke’s study was to determine the incidence, IR grade, timing, and completion of a rechallenge dose in patients who experienced an initial cetuximab IR. Secondary objectives included determining the incidence and IR grade that occurred with the administration of the first dose of cetuximab and identifying specific risk factors to further characterize patients who experienced an initial cetuximab IR. This retrospective, single-center study included patients with squamous cell carcinoma of the head and neck who were treated with cetuximab as monotherapy or in combination with chemotherapy between June 2008 and September 2015 at UKH or Westwood Cancer Center. Patients were excluded if they had previous exposure to cetuximab or received cetuximab outside of the UKH health system. IR were graded using the Common Terminology Criteria for Adverse Events (CTCAE v4.03).
Patients were categorized as either not experiencing an IR (NR = 132) or experiencing an IR (n = 33). Baseline patient characteristics of the two groups were similar. There was no statistically significant association between any of the patient-specific risk factors evaluated and the development of an initial IR. Risk factors assessed included receiving chemotherapy within the past 12 months, the treatment of the initial malignancy, single-agent chemotherapy, underlying respiratory disease, history of allergies, use of nonsedating allergy medication, and mean absolute neutrophil, lymphocyte, and eosinophil counts. Various combinations of premedications given prior to the initial IR also were assessed, and no statistical difference in the incidence of an initial IR was observed. Among patients who experienced an initial IR, none had a grade 1 IR, 87.9% had a grade 2 IR, 9.1% had a grade 3 IR, and 3% had a grade 4 IR. Approximately 88% of patients who experienced an initial IR were rechallenged, and all but one patient completed the rechallenge dose. Of those who were rechallenged, the majority (approximately 38%) received the rechallenge dose between 30–59 minutes after the initial dose.
This study found incidences of all grades of IR similar to those reported in clinical trials. However, this study demonstrated a much higher incidence of initial IR of grade 3/4 than that reported in clinical trials (12.1% versus 3%–5%). Dr. Burke’s study demonstrated that the majority of patients were able to be quickly and successfully rechallenged after an initial IR, which demonstrates that the institution’s current practice of same-day rechallenge is feasible and safe. Additional plans for this research include extending the study period to evaluate more patients.
Dr. Folan’s research, “Clinical Outcomes Associated with Linezolid-Resistant S. epidermidis Bloodstream Isolates in Leukemia Patients Empirically Treated with Linezolid,” was recognized with a Clinical/Translational Research Award. Staphyloccocus epidermidis is a common isolate in bloodstream infections among patients with hematologic malignancies. At the University of Texas MD Anderson Cancer Center, linezolid is used as empiric therapy in 85% of leukemia patients with febrile neutropenia. However, an estimated one-third of S. epidermidis bloodstream isolates in patients with leukemia at MD Anderson are resistant to linezolid; the clinical significance of this finding was unknown. The objective of Dr. Folan’s study was to assess short-term clinical outcomes in adult leukemia patients with linezolid-resistant S. epidermidis bloodstream infections treated empirically with linezolid. This retrospective, single-center cohort study included patients ≥18 years old with a primary diagnosis of leukemia who had at least one blood culture positive for S. epidermidis between June 2013 and July 2015 and for whom linezolid therapy was initiated within 1 day of the first positive blood culture.
The primary endpoint was a composite of short-term outcomes on day 3 including persistent fever (> 38° C), persistent S. epidermidis bacteremia, intensive care unit admission, and death from any cause. Secondary endpoints evaluated were individual components of the primary outcome, time to blood culture clearance, and time to hospital discharge from initial positive culture (within 10 days). These outcomes were compared between patients with linezolid-resistant isolates versus those with linezolid-susceptible strains. Of the 82 patients included in the study, 33 (40%) had a linezolid-resistant isolate, a substantial increase from the institution-specific rate of 5.5% in 2009. Patients with linezolid-resistant S. epidermidis tended to have worse short-term clinical outcomes as defined by the investigators’ composite endpoint compared to those with linezolid-sensitive organisms (60.7% versus 34.7%, p = 0.022). No differences existed between groups based on the individual components of the composite endpoint, with the exception of persistent bacteremia (36.4% versus 8.2%, p = 0.009). In addition, linezolid resistance was associated with a significantly longer median time to discharge. The study demonstrated that patients with a linezolid-resistant S. epidermidis bloodstream infection treated empirically with linezolid had significantly worse short-term clinical outcomes, primarily because of persistent bacteremia, as compared to patients with linezolid-susceptible isolates. Long-term morbidity is being assessed, and the results from Dr. Folan’s study will be used to discuss comprehensive treatment for leukemia patients with febrile neutropenia and gram positive bacteremia in light of the current resistance rates and antimicrobial usage trends at the institution.