Venous thromboembolism incidence and risk factors in adults with acute lymphoblastic leukemia treated with and without pegylated E. coli asparaginase-containing regimens.

PURPOSE: Asparaginases, key agents in treatment of acute lymphoblastic leukemia (ALL), are associated with venous thromboembolism (VTE). While risks of short-acting asparaginase-related VTE is well-known, we studied VTE incidence and risk factors in adult ALL patients treated with and without long-acting pegylated asparaginase (PegA). METHODS: Single-center, retrospective analysis of 89 ALL patients treated with (n = 61) or without (n = 28) PegA at Greenebaum Comprehensive Cancer Center. Reviewed patient and disease characteristics, treatment, and VTE incidence. RESULTS: VTE during treatment occurred in 31 patients (35%), and was associated with PegA (p = 0.001) and Philadelphia chromosome negativity (p = 0.002). Among PegA recipients, VTE was associated with a significantly higher mean body mass index (BMI) of 31.3 kg/m2 (p = 0.037), and was more common with pre-T/T cell compared to pre-B/B cell ALL (68.2% vs. 33.3%, p = 0.009). Antithrombin-III (ATIII) levels were measured for 26 patients; 16 (61.5%) were < 50%. Of those, 8 (50%) experienced VTE, while 3 of 10 (30%) patients with ATIII levels ≥ 50% experienced VTE. VTE occurred in 7 of 13 (54%) of patients who received ATIII repletion. There was a trend toward a higher incidence of VTE in the PegA group among patients with non-O compared to O blood type (55.9% vs. 33.3%, p = 0.079) as well as those with a higher hemoglobin at diagnosis (9.3 vs 8.1 g/dL, p = 0.056). CONCLUSION: This study confirms PegA as a risk factor for VTE in patients with ALL. Risk factors among those receiving PegA include higher BMI and pre-T/T cell ALL. ATIII repletion was not shown to be protective against VTE. There was a higher incidence of VTE in patients who received PegA with non-O compared to O blood type, but the precise correlation is uncertain.

Optimizing pegylated asparaginase use: An institutional guideline for dosing, monitoring, and management.

The incorporation of L-asparaginase and pegylated asparaginase into pediatric-inspired regimens has conferred a survival advantage in treatment of adults with acute lymphoblastic leukemia. Use of asparaginase products requires careful prevention, monitoring, and management of adverse effects including hypersensitivity, hepatotoxicity, pancreatitis, coagulopathy, and thrombosis. Currently, there is limited published literature to offer guidance on management of these toxicities. At the University of Maryland Marlene and Stewart Greenebaum Comprehensive Cancer Center, a standard of practice guideline was created to prevent and manage asparaginase-related adverse events. By sharing our long-term experience with asparaginase products and clinical management of asparaginase-induced toxicities, this article aims to improve patient safety and optimize treatment outcomes.

Real-world experience managing blinatumomab toxicities in adults with relapsed/refractory acute lymphoblastic leukemia.

PURPOSE: The purpose of this study was to determine the effect of blinatumomab toxicities on drug therapy modifications in an intended 28-day course of blinatumomab therapy. METHODS: Patients with acute lymphoblastic leukemia who received blinatumomab at the University of Maryland Marlene & Stewart Greenebaum Comprehensive Cancer Center from March 1, 2015 to April 30, 2018 were included. The primary objective of this study was to identify the frequency and severity of blinatumomab toxicities that led to drug therapy modifications; secondary objectives were to identify the frequency and duration of modifications and the total dose and duration of therapy received. RESULTS: This study included 23 patients. Seventy-eight percent of patients experienced cytokine release syndrome and/or neurotoxicity. Eighteen drug therapy modifications occurred due to toxicity with a median interruption time of nine hours. Drug therapy was continued for the majority of grade 1 or 2 events and discontinued during grade 3 or 4 neurotoxicity. The median number of days of therapy delivered was 28 days (range, 27-35). A median of 2 h (range, 0-16) of therapy or 0.2% (range, 0-2.4) of a total 28-day cycle was lost due to transition of care. CONCLUSION: This retrospective study demonstrates a single center experience with blinatumomab toxicity management and appropriate delivery of drug during transitions of care. Overall, these results support to the importance of institutional guidelines in place to facilitate safe and effective delivery of blinatumomab.

A single center retrospective analysis of a protocol for high-dose methotrexate and leucovorin rescue administration.

BACKGROUND: Methotrexate has a wide dosing range. High-dose methotrexate is a dose of 1000 mg/m2 or greater. In the 1970s, the incidence of mortality associated with High-dose methotrexate ranged from 4.6 to 6%. In 2012, the University of Maryland Medical Center implemented a standardized high-dose methotrexate protocol. The purpose of this study was to evaluate whether the institution followed recommendations based on the Bleyer nomogram for the administration of high-dose methotrexate more closely after the implementation of the protocol. METHODS: In this retrospective chart review, 37 patients received 119 cycles of high-dose methotrexate before the protocol implementation (1 January 2009 through 31 December 2010) and 45 patients received 106 cycles of high-dose methotrexate after protocol implementation (1 January 2013 through 31 December 2014). Patient characteristics, protocol data, and complications were analyzed. RESULTS: Protocol implementation significantly reduced the deviation of methotrexate level timing at 24, 48, and 72 h: median 7.47 vs. 1.46 h, 7.23 vs. 1.35 h, and 7.00 vs. 1.52 h before and after implementation, respectively (p < 0.0001 for each). The protocol significantly reduced deviation of the first dose of leucovorin administration: median 5.2 vs. 0.675 h before and after implementation, respectively (p<0.0001). After protocol implementation, there was an increase in the use of leucovorin prescriptions written appropriately for patients discharged before methotrexate levels reached a value of ≤0.05 µmol/L. CONCLUSIONS: Implementation of a protocol for the administration of high-dose methotrexate improved the adherence to consensus recommendations. Further analysis is needed to assess clinical pharmacist involvement and the cost savings implications within this protocol.

Assessing the need for improved strategies and medication-related education to increase adherence for oral anticancer medications in the young adult oncology population.

Rationale Oral anticancer medication adherence is a critical factor in optimizing cancer treatment outcomes and minimizing toxicity. Although potential adherence barriers exist, it is not well understood how these factors impact adherence. Methods This is a prospective, single-center, patient survey-based study conducted at the University of Maryland Greenebaum Comprehensive Cancer Center including 18- to 39-year-old patients who have been actively taking an oral anticancer medication for at least one month from 1 April 2013 to 1 April 2016. The primary objective of this study is to describe institutional practices for medication education and adherence monitoring practices as perceived by young adult patients at the University of Maryland Greenebaum Comprehensive Cancer Center and to describe practice consistency with recommendations from the American Society of Clinical Oncology/Oncology Nursing Society Chemotherapy Administration Safety Standards. The secondary objectives include patient-reported facilitators and barriers to oral anticancer medication adherence. Results Seventeen patients completed the survey; 24% ( n = 4) of patients denied receiving information about what to do in case of a missed dose. The most common facilitators of adherence include understanding of disease and treatment (88%, n = 15), perceived severity of illness (82%, n = 14), and use of oral anticancer medications (82%, n = 14). The most common barriers to adherence are side effects (59% n = 10), forgetfulness (47%, n = 8), and depressive symptoms (35%, n = 6). Conclusion Based on patient-reported guideline adherence, improvement is needed in including family, caregivers, and others in the education process as well as providing education about plan for missed doses and drug-drug and drug-food interactions. The strengths of the current medication education and adherence monitoring practices as perceived by the young adult patient population include education about the purpose and goals of treatment, the planned duration and schedule, side effects, and when to seek medical attention. The data collected from this survey can aid in future development and implementation of interventions aimed at improving medication adherence, such as integrating clinical pharmacy services into oral chemotherapy monitoring and education process.

Drug-drug interactions in patients receiving tyrosine kinase inhibitors.

Rationale Tyrosine kinase inhibitors are increasingly used in the treatment of cancer. Drug interactions involving tyrosine kinase inhibitors are commonly encountered in clinical practice. The objective of this study was to describe the frequency of tyrosine kinase inhibitor-associated drug interactions among a cohort of oncology patients. Methods Adult patients were included who presented to either of two outpatient oncology practices and were prescribed a tyrosine kinase inhibitor during 2 January 2013 to 1 January 2015. Demographic and medication data were abstracted from electronic medical records. Lexicomp®, Micromedex Solutions®, and medication labeling were utilized to identify potential interactions between tyrosine kinase inhibitors and concomitant medications. Interactions were then assessed by the investigators for clinical significance. The primary outcome was the frequency of significant drug interactions involving tyrosine kinase inhibitors and concomitant medications. Secondary outcomes included describing the nature and clinical impact of interactions, and describing interactions by medication class. Results A total of 356 patients were identified for analysis, in whom 244 potential interactions were identified, and 109 (44.7%) of which were considered severe. Decreased tyrosine kinase inhibitor absorption due to acid suppressive therapy and CYP3A4 interactions were the most frequent mechanisms of potential subtherapeutic and supratherapeutic concentrations, respectively. Potential clinical consequences included QTc prolongation ( n = 53, 48.6%), decreased tyrosine kinase inhibitor concentration ( n = 53, 48.6%), and increased tyrosine kinase inhibitor concentration ( n = 3, 2.8%). Conclusions Safer alternative therapy and/or more frequent clinical monitoring should be considered if an interaction poses a significant risk of increased tyrosine kinase inhibitor toxicity or decreased tyrosine kinase inhibitor efficacy. Oncology pharmacists can play a role in screening for tyrosine kinase inhibitor-associated interactions, recommending alternative therapies or dosing strategies, and monitoring tyrosine kinase inhibitor efficacy and toxicity.