Rational use of rasburicase for the treatment and management of tumor lysis syndrome.

Purpose There is a lack of high-level evidence identifying meaningful outcomes and the optimal place in therapy of rasburicase in patients with, or at high risk for tumor lysis syndrome. The primary objective of this study was to evaluate and characterize outcomes resulting from an institution-specific guideline emphasizing supportive care, xanthine oxidase inhibitors, and lower doses of rasburicase. Methods In this retrospective chart review, we compared conservative rasburicase dosing, in accordance with newly developed UMHS tumor lysis syndrome guidelines, with aggressive rasburicase in adult patients (≥ 18 years of age) with hematological or solid tumor malignancies, and a uric acid level between 8 and 15 mg/dL. The primary efficacy outcome assessed the difference in the proportion of patients achieving a uric acid level <8 mg/dL within 48 h using a one-sided noninferiority test. The principle safety outcomes analyzed included incidence of acute kidney injury and hemodialysis requirement. Results One hundred sixty-one patients met inclusion criteria and were included in the study. Within 48 h of an elevated uric acid level, treatment was successful in 97.03% of patients in the conservative group, as compared with 98.33% in the aggressive group (difference, 1.3 percentage points; 95% confidence interval [CI], -3.33 to 5.93). Furthermore, there was no difference in the proportion of patients requiring hemodialysis (2.97% vs. 10.0%, p-value 0.079), or incidence of acute kidney injury (4.0% vs. 12.5%, p-value 1.00) between the treatment group and control group, respectively. Conclusions Conservative rasburicase use was noninferior to aggressive rasburicase use in patients with or at high risk for tumor lysis syndrome.

Risk factors for piperacillin/tazobactam-resistant Gram-negative infection in hematology/oncology patients with febrile neutropenia.

PURPOSE: Febrile neutropenia (FN) is a life-threatening complication of cancer therapy, and initial ineffective therapy is associated with poor outcomes. Piperacillin/tazobactam (PTZ) is a commonly used empiric antibiotic for the treatment of FN, but resistance among Gram-negative pathogens is well described. We conducted a retrospective case-control study to identify risk factors for PTZ-resistant (PTZ-R) Gram-negative isolates. METHODS: Hematology/oncology patients with FN from November 2007 to November 2013 with a positive culture for Gram-negative bacilli were divided into two groups: PTZ-sensitive (PTZ-S) and PTZ-R. A multivariable model using logistic regression was constructed to identify risk factors for PTZ-R. RESULTS: A total of 171 patients were included (25 PTZ-R, 146 PTZ-S), yielding a 14.6 % resistance rate. Thirty-day all-cause mortality was significantly higher in the PTZ-R group (29 vs 11 %, P = 0.024). Multivariable analysis yielded intensive care unit (ICU) status (odds ratio (OR) 20.18; 95 % confidence interval (CI) 1.03-397.35; P = 0.048), antibiotics for > 14 days in the previous 90 days (OR 6.02; CI 1.17-30.93; P = 0.032), and respiratory source (OR 13.65; CI 1.14-163.57; P = 0.039) as significant risk factors for PTZ-R, and the receiver operating characteristic area under the curve of the model was 0.894. Among PTZ-R isolates, 88 % were sensitive to meropenem and 100 % were sensitive to amikacin. CONCLUSIONS: Given the high mortality rates in the PTZ-R group, a risk-factor-guided approach driven by this multivariable model may help identify patients that could benefit from amikacin combination therapy to help optimize empiric therapy in this setting.

Financial Impact of an Automated Oncology Dose-Rounding Initiative: One-Year Analysis.

PURPOSE: Infusion drugs are regarded as one of the high-cost health care expenditures. One approach to decrease drug expenditures is by dose-rounding biologics and cytotoxic agents. The Hematology/Oncology Pharmacy Association recommends that biologic and cytotoxic agents are rounded to the nearest vial size if they are within 10% of the ordered dose. The purpose of this initiative is to determine the impact of an automated dose-rounding algorithm on drug expenses. METHODS: The dose-rounding algorithm was developed and integrated into the computerized physician order entry system for automated dose rounding to minimize impact on current workflow and to reduce medication errors. Twenty-four medications were preselected for dose rounding and included in the analysis. Ordered doses were automatically rounded to the nearest vial size if the dose was within 10% of the original dose. Prescribers then either reviewed and signed the rounded dose or manually entered the nonrounded dose. Cost savings were calculated as drug expense savings from doses rounded down. RESULTS: From July 2018 to June 2019, 10,206 doses of the selected medications were administered. Dose rounding occurred in 5,069 doses (49.7%). All 24 medications within the initiative were administered within the time of analysis. Of the rounded doses administered, 2,516 (49.6%) were rounded down to a commercially available vial size. Using wholesale acquisition cost pricing, the drug expense savings was approximately $3.6 million US dollars (USD). The medications with the highest savings were trastuzumab and ipilimumab, with annual savings of $756,780 USD and $494,517 USD, respectively. CONCLUSION: The automated dose-rounding algorithm at Michigan Medicine reduced drug expenditures substantially, and its integration within the computerized physician order entry system had minimal impact on current workflow.

Clinical developments in the treatment of relapsed or relapsed and refractory multiple myeloma: impact of panobinostat, the first-in-class histone deacetylase inhibitor.

BACKGROUND: Panobinostat is a new agent for the treatment of relapsed and refractory multiple myeloma (rrMM) as part of a combination regimen. This article presents an overview of the mechanism of action, pharmacokinetics, safety, efficacy, patient care strategies, and role of the agent in treating rrMM patients. RESULTS: Panobinostat belongs to the class of drugs known as histone deacetylase inhibitors, and has high activity against Class I, II, and IV nonhistone deacetylases and histone deacetylases. It represents the first of its class to receive approval for use in MM, and received priority review and orphan drug status in both US and Europe, when used in combination with bortezomib and dexamethasone in the treatment of rrMM. Approval of panobinostat was based on subgroup analysis of Phase III data obtained in the PANORAMA trial program for evaluation of the combination of panobinostat, bortezomib, and dexamethasone. Additional clinical trials have continued to explore optimal dosing regimens and novel combination regimens to further clarify the optimal role of panobinostat in the arsenal of drugs for rrMM. Panobinostat has shown a manageable safety profile characterized primarily by hematologic toxicities (thrombocytopenia, neutropenia, lymphopenia, and anemia), gastrointestinal toxicities, notably diarrhea and nausea, as well as fatigue/asthenia, electrolyte abnormalities, and less commonly cardiac toxicities. CONCLUSION: Panobinostat represents an important addition to the treatment armamentarium for patients with rrMM, and studies are underway evaluating its optimal dosing strategy and role in combination with other drugs used to treat this patient population.