A comparative review of Aphexda and Mozobil for mobilization prior to stem cell collection.

High-dose chemotherapy followed by autologous hematopoietic stem cell transplantation is the standard of care for eligible patients with newly diagnosed multiple myeloma leading to prolonged progression free and overall survival. Successful engraftment following hematopoietic stem cell infusion requires adequate stem cell doses. Current mobilization regimens include granulocyte colony-stimulating factor (G-CSF) with or without plerixafor. Motixafortide is a recently approved agent that can be used in combination with G-CSF for mobilization. In the absence of any head-to-head trials comparing the two products, this article aims to outline the similarities and differences of these two agents. Though moxitafortide has a more favorable pharmacokinetic profile in comparison to plerixafor, in clinical trials, the agents demonstrated similar efficacy. In addition, the use of motixafortide in clinical practice may be limited by product cost as well as administration and monitoring requirements.

Pilot Study of a Mobile Phone Chatbot for Medication Adherence and Toxicity Management Among Patients With GI Cancers on Capecitabine.

PURPOSE: Capecitabine is an oral chemotherapy used to treat many gastrointestinal cancers. Its complex dosing and narrow therapeutic index make medication adherence and toxicity management crucial for quality care. METHODS: We conducted a pilot study of PENNY-GI, a mobile phone text messaging-based chatbot that leverages algorithmic surveys and natural language processing to promote medication adherence and toxicity management among patients with gastrointestinal cancers on capecitabine. Eligibility initially included all capecitabine-containing regimens but was subsequently restricted to capecitabine monotherapy because of challenges in integrating PENNY-GI with radiation and intravenous chemotherapy schedules. We used design thinking principles and real-time data on safety, accuracy, and usefulness to make iterative refinements to PENNY-GI with the goal of minimizing the proportion of text messaging exchanges with incorrect medication or symptom management recommendations. All patients were invited to participate in structured exit interviews to provide feedback on PENNY-GI. RESULTS: We enrolled 40 patients (median age 64.5 years, 52.5% male, 62.5% White, 55.0% with colorectal cancer, 50.0% on capecitabine monotherapy). We identified 284 of 3,895 (7.3%) medication-related and 13 of 527 (2.5%) symptom-related text messaging exchanges with incorrect recommendations. In exit interviews with 24 patients, participants reported finding the medication reminders reliable and user-friendly, but the symptom management tool was too simplistic to be helpful. CONCLUSION: Although PENNY-GI provided accurate recommendations in >90% of text messaging exchanges, we identified multiple limitations with respect to the intervention's generalizability, usefulness, and scalability. Lessons from this pilot study should inform future efforts to develop and implement digital health interventions in oncology.

Effectiveness, Safety, and Cost Implications of Outpatient Autologous Hematopoietic Stem Cell Transplant for Multiple Myeloma.

BACKGROUND AND OBJECTIVE: Autologous hematopoietic stem cell transplant (aHCT) has become standard care for patients with multiple myeloma (MM). Outpatient aHCT with high-dose melphalan conditioning has reduced costs and length of hospital stay. This study aimed to highlight the effectiveness, safety, and cost implications of outpatient vs inpatient aHCT at a tertiary academic medical center, as well as the utility of growth factor use in these patients. PATIENTS AND METHODS: Using an institutional HCT database, a total of 100 patients undergoing aHCT for MM were identified; 50 patients who underwent aHCT in the outpatient setting (chemotherapy and stem cell infusion followed by inpatient admission if needed) were compared with 50 patients in the inpatient setting (chemotherapy and stem cell infusion followed by discharge to outpatient setting). Patients were excluded if the melphalan dose was less than 200 mg/m2. Outcomes assessed through retrospective chart review included time to engraftment, incidence of infection, febrile neutropenia, growth factor use, and total length of inpatient stay through day +100. RESULTS: Time to neutrophil and platelet engraftment was shorter in the outpatient group than in the inpatient group (14 vs 16 days and 19 vs 21 days, respectively; P < 0.001). Median length of hospital stay was also shorter in the outpatient group (8.5 vs 15.5 days, respectively; P < 0.001). Ninety percent of the outpatient group required admission for neutropenic fever, and 60% of these patients received growth factor support starting at a median of 9 days after stem cell infusion, for a median duration of 4 days. Compared to 16 patients who did not receive growth factor support, these patients had a significantly shorter time to neutrophil recovery (13 days with vs 15 days without growth factor, P = 0.02) and no difference in the total length of hospital stay (8 days with vs 10 days without growth factor, P = 0.43). CONCLUSION: For adult patients with MM undergoing aHCT, the outpatient setting is safe and reduces the total length of hospital stay and thus overall transplant costs. Growth factor support for patients with febrile neutropenia may not reduce length of stay for subsequent hospitalizations.

Implementing Pharmacogenetic Testing in Gastrointestinal Cancers (IMPACT-GI): Study Protocol for a Pragmatic Implementation Trial for Establishing DPYD and UGT1A1 Screening to Guide Chemotherapy Dosing.

Background: Fluoropyrimidines (fluorouracil [5-FU], capecitabine) and irinotecan are commonly prescribed chemotherapy agents for gastrointestinal (GI) malignancies. Pharmacogenetic (PGx) testing for germline DPYD and UGT1A1 variants associated with reduced enzyme activity holds the potential to identify patients at high risk for severe chemotherapy-induced toxicity. Slow adoption of PGx testing in routine clinical care is due to implementation barriers, including long test turnaround times, lack of integration in the electronic health record (EHR), and ambiguity in test cost coverage. We sought to establish PGx testing in our health system following the Exploration, Preparation, Implementation, Sustainment (EPIS) framework as a guide. Our implementation study aims to address barriers to PGx testing. Methods: The Implementing Pharmacogenetic Testing in Gastrointestinal Cancers (IMPACT-GI) study is a non-randomized, pragmatic, open-label implementation study at three sites within a major academic health system. Eligible patients with a GI malignancy indicated for treatment with 5-FU, capecitabine, or irinotecan will undergo PGx testing prior to chemotherapy initiation. Specimens will be sent to an academic clinical laboratory followed by return of results in the EHR with appropriate clinical decision support for the care team. We hypothesize that the availability of a rapid turnaround PGx test with specific dosing recommendations will increase PGx test utilization to guide pharmacotherapy decisions and improve patient safety outcomes. Primary implementation endpoints are feasibility, fidelity, and penetrance. Exploratory analyses for clinical effectiveness of genotyping will include assessing grade ≥3 treatment-related toxicity using available clinical data, patient-reported outcomes, and quality of life measures. Conclusion: We describe the formative work conducted to prepare our health system for DPYD and UGT1A1 testing. Our prospective implementation study will evaluate the clinical implementation of this testing program and create the infrastructure necessary to ensure sustainability of PGx testing in our health system. The results of this study may help other institutions interested in implementing PGx testing in oncology care. Clinical Trial Registration: https://clinicaltrials.gov/ct2/show/NCT04736472, identifier [NCT04736472].

Custom cerium oxide nanoparticles protect against a free radical mediated autoimmune degenerative disease in the brain.

Cerium oxide nanoparticles are potent antioxidants, based on their ability to either donate or receive electrons as they alternate between the +3 and +4 valence states. The dual oxidation state of ceria has made it an ideal catalyst in industrial applications, and more recently, nanoceria's efficacy in neutralizing biologically generated free radicals has been explored in biological applications. Here, we report the in vivo characteristics of custom-synthesized cerium oxide nanoparticles (CeNPs) in an animal model of immunological and free-radical mediated oxidative injury leading to neurodegenerative disease. The CeNPs are 2.9 nm in diameter, monodispersed and have a -23.5 mV zeta potential when stabilized with citrate/EDTA. This stabilizer coating resists being 'washed' off in physiological salt solutions, and the CeNPs remain monodispersed for long durations in high ionic strength saline. The plasma half-life of the CeNPs is ∼4.0 h, far longer than previously described, stabilized ceria nanoparticles. When administered intravenously to mice, the CeNPs were well tolerated and taken up by the liver and spleen much less than previous nanoceria formulations. The CeNPs were also able to penetrate the brain, reduce reactive oxygen species levels, and alleviate clinical symptoms and motor deficits in mice with a murine model of multiple sclerosis. Thus, CeNPs may be useful in mitigating tissue damage arising from free radical accumulation in biological systems.