Impact of electronic interventions on guideline concordant ordering of rituximab infusion rate.

INTRODUCTION: Rituximab carries a boxed warning for severe or fatal infusion reactions; most occurring with the initial infusion. Prior studies established that if the initial rituximab infusion is tolerated, subsequent infusions can be given safely over 90 min. The University of Chicago Medicine (UCM) did not have a standardized method to document infusion reactions for outpatient chemotherapy patients, making it challenging for providers to know a patients' eligibility for rapid infusion. This quality improvement project focused on a series of interventions to improve documentation and electronic ordering of rituximab. METHODS: A flowsheet for nurses to record patients' tolerance of chemotherapy infusions was created within the electronic health record (EHR). Following results of flowsheet impact, a second intervention was implemented to modify ordering of rituximab. The primary endpoint was the incidence of guideline concordant rate ordering of rituximab. Secondary endpoints included the incidence of accurate chair time scheduling pre- and post-interventions and nursing compliance with flowsheet documentation. RESULTS: Prior to flowsheet implementation, 85% of patients were infused at the guideline concordant rate, compared to 79% post-implementation. Prior to modification of rituximab ordering in the EHR, 85% of patients were infused at the guideline concordant rate, compared to 87% after implementation. Complete nursing documentation was done 89% of the time when the flowsheet was utilized, compared to 11% pre-interventions. CONCLUSION: No difference in primary or secondary endpoints was found following our interventions. However, the infusion documentation flowsheet, when used, provided more complete reaction data compared to when it was not used.

Changes in Intravenous Immunoglobulin Usage for Hypogammaglobulinemia After Implementation of a Stewardship Program.

PURPOSE: Intravenous immunoglobulin (IVIG) is used to replenish immunoglobulins in hypogammaglobulinemia (HG) caused by hematologic malignancies (HM) or their treatment (autologous stem-cell transplantation [ASCT] and chimeric antigen receptor T-cell therapy [CAR-T]), in an effort to reduce the risk of infections. However, there is limited evidence to support this use, and IVIG supplies are limited and shortages are common. METHODS: An IVIG stewardship program (ISP) was implemented with the following requirements for IVIG administration: immunoglobulin G (IgG) level < 400 mg/dL (corrected for paraprotein) for post-ASCT and post-CAR-T patients, or IgG < 400 mg/dL with a history of a bacterial infection within the preceding 3 months for those with HM. Comparisons of the amount of IVIG administered, the incidence of infections, and the use of antimicrobials were performed between the 3 months before ISP and the 3 months after ISP. RESULTS: IVIG administered for HG decreased from 4,902 g in 86 patients before ISP to 1,777 g in 55 patients after ISP, a cost savings of $44,700. Adherence to ISP guidelines was 80%. Compared with before ISP, patients who stopped receiving IVIG after ISP had lower nadir IgG, fewer infections/patient-months, less antimicrobial usage, and a lower hospitalization rate for infection; no deaths occurred. Compared with before ISP, patients receiving IVIG after ISP had lower predose IgG and fewer infections/patient-months; the antibiotic usage, hospitalization rate for infection, and deaths from infection remained stable. CONCLUSION: To our knowledge, this is the first ISP to lead to a dramatic decrease in IVIG usage with high adherence, primarily by selecting out patients at low risk of infection after IVIG discontinuation. Such an ISP is replicable and warrants adoption.

Impact of an Oncology Clinical Pharmacist Specialist in an Outpatient Multiple Myeloma Clinic.

INTRODUCTION: Improvements in cancer treatment and supportive care, as well as the approval of oral chemotherapy medications over the past decade, have resulted in an increasing number of cancer patients being treated in outpatient settings. Transitioning cancer treatments to the outpatient setting places greater emphasis on proper medication counseling and optimal management of adverse effects. We therefore evaluated the clinical and financial impact of an oncology clinical pharmacist specialist in an interdisciplinary multiple myeloma clinic by using a validated scoring tool. METHODS: The oncology clinical pharmacist specialist was available for consult by the multiple myeloma clinic staff. The pharmacist may be consulted for any medication-related inquiry. On the basis of the consult, the pharmacist categorized interventions into 12 predefined intervention categories. RESULTS: Implementation of a clinical pharmacy specialist into a multiple myeloma clinic over 39 clinic days resulted in 241 patient consults and 474 interventions made by the pharmacist. The most frequent interventions made by the pharmacist were medication teaching (n = 97), dose adjustments (n = 82), and medication reconciliation (n = 63). The value of interventions made by the pharmacist during the study period was $189,441, with a predicted annual value of $757,764. CONCLUSION: The addition of an oncology pharmacist to an outpatient multiple myeloma clinic can improve clinical and financial outcomes.

HIPEC with cisplatin in a patient with a prior hypersensitivity reaction to systemic oxaliplatin.

Platinum-based chemotherapeutic agents are commonly used in the treatment of several cancers. While effective, they are often discontinued due to toxicities and hypersensitivity reactions (HSRs) that occur more frequently with repeated exposure. Following discontinuation of one agent, therapy may be continued with a second platinum salt, though the cross-reactivity between agents in this class is not well understood. This is particularly true for alternative routes of administration such as hyperthermic intraperitoneal chemotherapy (HIPEC). In this case report, we describe the use of cisplatin during HIPEC in a patient who previously experienced an HSR to systemic oxaliplatin. The patient tolerated HIPEC including 200 mg cisplatin for 1 hour without any adverse effects and did not require a desensitization protocol prior to therapy. This case suggests that HIPEC with platinum-based agents can be performed in patients with prior HSRs to systemic therapy, though further studies are needed to understand safety parameters, the cross-reactivity between agents and the necessity of skin testing or desensitization protocols.

Implementation of pharmacogenomic testing in oncology care (PhOCus): study protocol of a pragmatic, randomized clinical trial.

BACKGROUND: Many cancer patients who receive chemotherapy experience adverse drug effects. Pharmacogenomics (PGx) has promise to personalize chemotherapy drug dosing to maximize efficacy and safety. Fluoropyrimidines and irinotecan have well-known germline PGx associations. At our institution, we have delivered PGx clinical decision support (CDS) based on preemptively obtained genotyping results for a large number of non-oncology medications since 2012, but have not previously evaluated the utility of this strategy for patients initiating anti-cancer regimens. We hypothesize that providing oncologists with preemptive germline PGx information along with CDS will enable individualized dosing decisions and result in improved patient outcomes. METHODS: Patients with oncologic malignancies for whom fluoropyrimidine and/or irinotecan-inclusive therapy is being planned will be enrolled and randomly assigned to PGx and control arms. Patients will be genotyped in a clinical laboratory across panels that include actionable variants in UGT1A1 and DPYD. For PGx arm patients, treating providers will be given access to the patient-specific PGx results with CDS prior to treatment initiation. In the control arm, genotyping will be deferred, and dosing will occur as per usual care. Co-primary endpoints are dose intensity deviation rate (the proportion of patients receiving dose modifications during the first treatment cycle), and grade ⩾3 treatment-related toxicities throughout the treatment course. Additional study endpoints will include cumulative drug dose intensity, progression-free survival, dosing of additional PGx supportive medications, and patient-reported quality of life and understanding of PGx. DISCUSSION: Providing a platform of integrated germline PGx information may promote personalized chemotherapy dosing decisions and establish a new model of care to optimize oncology treatment planning.

The impact of initiating posaconazole on tacrolimus pharmacokinetics in allogeneic stem cell transplantation.

BACKGROUND: Posaconazole reduces the risk of invasive Aspergillus in transplant patients, but significantly inhibits tacrolimus metabolism. One study demonstrated that a three-fold dose reduction of tacrolimus was required to obtain therapeutic concentrations when used with posaconazole. However, with empiric dose reduction, there is a risk of subtherapeutic tacrolimus levels and subsequent graft failure or graft-versus-host disease. Overall, the existing data on the impact of posaconazole on tacrolimus pharmacokinetics is limited. OBJECTIVE: The purpose of this study is to determine whether tacrolimus doses should be decreased upon initiation of posaconazole in patients receiving an allogeneic stem cell transplant. METHODS: This is a retrospective chart review at an academic medical center. All allogeneic stem cell transplant adults who received concomitant posaconazole and tacrolimus from February 2016 through December 2017 were included. RESULTS: Seventy-nine patients identified using an internal electronic database were analyzed. The median time to therapeutic tacrolimus concentration was significantly longer in patients who did not receive an empiric dose reduction (0% DR, 10d; 1-30% DR, 4d; 31-65% DR, 5d; >65% DR, 4d; p = 0.0395). The rate of supratherapeutic levels was highest amongst patients who did not receive an empiric DR, and was noted to be significant compared to the group that had 31-65% DR (p < 0.001). CONCLUSION: This study validates our current practice of instituting an empiric 50% dose reduction of oral tacrolimus to 0.03 mg/kg/day when used concomitantly with posaconazole to achieve therapeutic levels in allogeneic stem cell transplant patients.

Pharmacy Operationalization of the Intralesional Oncolytic Immunotherapy Talimogene Laherparepvec.

Objective: Oncolytic immunotherapy involves the use of viruses to target and destroy cancer cells and to induce immune responses for an enhanced antitumor effect. Talimogene laherparepvec, a genetically modified herpes simplex virus type 1 (HSV-1) that selectively replicates in tumors to induce lytic cell death, tumor antigen release, and the local production of granulocyte-macrophage colony-stimulating factor (GM-CSF), has been approved for the treatment of a defined population of patients with metastatic melanoma. Talimogene laherparepvec is administered as a series of intralesional injections, and specific procedures are implemented to minimize the risk of viral exposure. Because talimogene laherparepvec represents a novel therapeutic modality, its preparation, administration, and handling requirements differ from current therapies; pharmacists have an important role in developing new procedures to incorporate it into clinical practice. Methods: In this review, pharmacists with experience dispensing talimogene laherparepvec, in the clinical trial setting and/or as a commercially available product at US academic institutions, synthesized their personal experiences through group discussions to provide insights on the ordering, receipt, storage, preparation, administration, and handling of talimogene laherparepvec. Results: Suggestions for patient education and practical guidance to assist hospital pharmacists and decision makers with implementing talimogene laherparepvec at their institutions are provided. Conclusion: These insights may further inform the development of policies or procedures to incorporate talimogene laherparepvec into clinical settings and improve patient outcomes.

Biosimilars in Oncology in the United States: A Review.

IMPORTANCE: Biosimilars are biological medicines that contain a highly similar version of the active substance of an already approved biologic reference product. The availability of biosimilars might provide an opportunity to lower health care expenditures as a result of the inherent price competition with their reference product. Understanding how biosimilar cancer drugs are regulated, approved, and paid for, as well as their impact in a value-based care environment, is essential for physicians and other stakeholders in oncology. OBSERVATIONS: Important structural and regulatory differences exist between biosimilar and generic medications. Minor differences in clinically inactive components with no clinically meaningful differences between biosimilars and their reference biologic are allowed. A biosimilar uses the same mechanism of action as the reference biologic, and its condition of use is the same as the approved indication, although extrapolation is permitted across indications under regulatory guidance. A biosimilar has to have a similar route of administration, dosage, and strength as the reference biologic. As patent expiration of multiple cancer biologics will occur in the next few years, more biosimilars might enter the market. Whether the approval and use of biosmilars as replacements for these heavily prescribed reference biologics will ultimately lead to cost savings is unknown and requires longer follow-up. Two biosimilars with an oncology supportive care indication are currently approved in the United States; both are myeloid growth factors. CONCLUSIONS AND RELEVANCE: The financial impact of generic drug competition can be dramatic, but significant differences in regulatory and development processes between generics and biosimilars limit such comparisons and likely present significant challenges for biosimilar approval and adoption in the US market. However, a value-based care environment and their cost-savings potential make biosimilars an attractive option for the therapeutic arsenal. Oncologists' understanding of biosimilars is critical to moving forward.

Impact of a clinical pathway on appropriate empiric vancomycin use in cancer patients with febrile neutropenia.

Objectives Febrile neutropenia management guidelines recommend the use of vancomycin as part of an empiric antimicrobial regimen when specific criteria are met. Often, vancomycin use among patients with febrile neutropenia is not indicated and may be over utilized for this indication. We sought to evaluate the impact of implementing a febrile neutropenia clinical pathway on empiric vancomycin use for febrile neutropenia and to identify predictors of vancomycin use when not indicated. Methods Adult febrile neutropenia patients who received initial therapy with an anti-pseudomonal beta-lactam with or without vancomycin were identified before (June 2008 to November 2010) and after (June 2012 to June 2013) pathway implementation. Patients were assessed for appropriateness of therapy based on whether the patient received vancomycin consistent with guideline recommendations. Using a comorbidity index used for risk assessment in high risk hematology/oncology patients, we evaluated whether specific comorbidities are associated with inappropriate vancomycin use in the setting of febrile neutropenia. Results A total of 206 patients were included in the pre-pathway time period with 35.9% of patients receiving vancomycin therapy that was inconsistent with the pathway. A total of 131 patients were included in the post-pathway time period with 11.4% of patients receiving vancomycin inconsistent with the pathway ( p = 0.001). None of the comorbidities assessed, nor the comorbidity index score were found to be predictors of vancomycin use inconsistent with guideline recommendations. Conclusion Our study has demonstrated that implementation of a febrile neutropenia pathway can significantly improve adherence to national guideline recommendations with respect to empiric vancomycin utilization for febrile neutropenia.

BK virus infection is associated with hematuria and renal impairment in recipients of allogeneic hematopoetic stem cell transplants.

BK virus (BKV) is an important pathogen and cause of nephropathy in renal transplant recipients, but its significance following hematopoetic stem cell transplantation (HSCT) is less well described. We measured blood and urine BKV in 124 allogeneic HSCT patients (67 had undergone prior HSCT [surveillance cohort]; 57 were monitored from transplant day 0 [prospective cohort]). BK viruria was manifest in 64.8% of the patients; 16.9% developed viremia. In the prospective cohort, the median time from transplantation to BK viremia development (128 days) was longer than for viruria (24 days; P < .0001). Among clinical factors (sex, disease, transplant type, alemtuzumab use, cytomegalovirus [CMV] viremia, graft-versus-host disease [GVHD], donor HLA C7 allele), only CMV viremia was more common in patients with BKV infection (P < or = .04). There was a direct relationship between blood and urine BKV levels and the occurrence, and degree, of hematuria (P < or = .03). Finally, BKV infection was analyzed along with other clinical factors in relation to the development of post-HSCT renal impairment. On multivariate analysis, only BK viremia (P=.000002) and alternative-donor transplantation (P=.002) were independent predictors of development of post-HSCT renal impairment, with BK viremia associated with a median 1.62mg/dL rise in creatinine from the pretransplant baseline. Among 8 patients in the surveillance cohort with BK viremia, 2 developed biopsy-proven BKV nephropathy requiring hemodialysis. Investigation of whether prophylaxis against, or treatment of, BKV in the post-HSCT setting mitigates the associated morbidities, especially kidney injury, warrants prospective evaluation.