Clinical utility of a regional precision medicine molecular tumor board and challenges to implementation.

PURPOSE: Molecular tumor boards provide precision treatment recommendations based on cancer genomic profile. However, practical barriers limit their benefits. We studied the clinical utility of the precision medicine molecular tumor board (PMMTB) and described challenges with PMMTB implementation. METHODS: An observational cohort study included patients reviewed by the PMMTB between September 2015 to December 2017. Patients who had consented to the registry study were included. The primary endpoint of this study was time on treatment (ToT) ratio. Clinical utility was established if the primary endpoint had least 15% of patients achieving a ToT ratio of ≥1.3. RESULTS: Overall, 278 patients were presented to the PMMTB and 113 cases were included in the final analysis. The PMMTB identified at least one nonstandard of care (SOC) clinically actionable mutation for 69.0% (78/113) of cases. In patients who received non-SOC treatment, 43.8% (7/16) achieved a ToT ratio of 1.3 or more (p < 0.001). Fifty-nine patients did not receive non-SOC recommendations. Reasons for not pursuing treatment included 35.6% having response to current treatment, 20.3% died prior to starting or considering PMMTB recommendations, 13.6% pursued other treatment options based on clinician discretion, another 10.2% pursued other treatment options because clinical trials recommended were not geographically accessible, 8.5% had rapid decline of performance status, 6.8% lacked of financial support for treatment, and 5.1% were excluded from clinical trials due to abnormal laboratory values. CONCLUSION: The regional PMMTB non-SOC recommendations benefitted a majority of patients and additional processes were implemented to assist with non-SOC treatment accessibility.

Unleashing the power of immunotherapy and targeted therapy combinations: Advancing cancer care or discovering unknown toxicities?

OBJECTIVE: The purpose of this review was to summarize the triumphs and pitfalls of tyrosine kinase inhibitor (TKI) and immune checkpoint inhibitor (ICI) combinations.Data sources: A literature review of PubMed was conducted and studies were included if they were classified as a clinical trial and assessed TKI and ICI combinations for solid tumor malignancies. Dates of literature search included January 1, 1988 through September 22, 2019.Data summary: In the past decade, TKI and ICI monotherapy strategies have changed the management of many advanced solid tumors through their unique mechanisms of action. Preclinical data suggests that TKIs may be able to sensitize tumors to ICI therapy via direct and indirect pathways; however, optimal mechanisms to support various TKI and ICI combinations have yet to be determined. The FDA recently approved TKI and ICI combinations for renal cell carcinoma, endometrial carcinoma, and melanoma. Several other tumor types currently have TKI and immunotherapy combinations under investigation with mixed results. Dual therapy with TKIs and immunotherapy have the potential to be synergistic and improve patient outcomes; however, careful consideration will need to be taken in regard to what TKI and immunotherapy are combined. CONCLUSIONS: Future research will be needed to determine appropriate sequencing of TKIs and ICIs after progression on combination therapy. Continued research is necessary to determine optimal dual TKI and immunotherapy options.

Extemporaneous compounding and administration of tretinoin slurry for acute promyelocytic leukemia.

INTRODUCTION: Acute promyelocytic leukemia (APL) is a potentially curable malignancy with 4-year overall survival rates >90%. Early complications from the disease or its treatment may result in a loss of oral access and require alternative administration of medications. Tretinoin has been the backbone of APL therapy since the late 1990s and is only available as a liquid filled capsule. CASE REPORT: Two patients with high-risk APL were unable to safely swallow tretinoin capsules due to complications of their disease. MANAGEMENT & OUTCOME: We prepared a tretinoin slurry using tretinoin 10 mg capsules, sterile water, and mineral oil at a ratio of 1 capsule to 2.75 mL sterile water to 1.25 mL mineral oil. This was successfully administered to both patients and no doses of tretinoin slurry were missed by either patient. In the patient who has long-term follow up available, a complete remission was achieved. DISCUSSION: Due to tretinoin's known teratogenicity, this capsule should not be crushed, cut, or open, which limits its use in patients without oral access. Alternative routes of administration, such as via a nasogastric tube or sublingually, have not been safe and effective. By preparing a tretinoin slurry in our hazardous extemporaneous compounding area, we were able to safely and effectively prepare a tretinoin slurry that was successfully administered to two patients. This alternative preparation did not alter long-term outcomes and represents a viable option for patients who do not have oral access.

Flat-dose granulocyte colony-stimulating factor evaluation after autologous hematopoietic stem cell transplant in multiple myeloma patients: Does one dose fit all?

INTRODUCTION: The current recommended granulocyte-colony stimulating factor (G-CSF) dose after autologous hematopoietic stem cell transplant (autoHSCT) in multiple myeloma patients is 5 mcg/kg/day administered subcutaneously until engraftment. Recently, our institution changed practice from weight-based to flat-dose G-CSF. The purpose of this study was to assess the impact of flat-dose G-CSF on time to engraftment among multiple myeloma patients of different weight groups. METHODS: Retrospective chart review was completed for adult patients with multiple myeloma who underwent autoHSCT from March 2018 through August 2019. Data collected included time to neutrophil engraftment, total length of hospitalization, length of stay post-transplant, time to platelet engraftment, use of intravenous fluconazole or acyclovir, parenteral nutrition use, incidence of febrile neutropenia, antibiotic use, and death. Differences in outcomes were compared between patients ≤80 kg versus those >80 kg. A secondary analysis was completed for patients ≤100 kg versus those >100 kg. RESULTS: There was no difference in time to neutrophil engraftment between weight groups (≤80 kg versus >80 kg: median = 12 days, p = 0.22; ≤100 kg versus >100 kg: median = 12 days, p = 0.52). There was a significant difference in intravenous fluconazole and acyclovir use between groups, with more use in the lower weight groups (≤80 kg versus >80 kg: 12 patients versus 10 patients p = 0.02; ≤100 kg versus >100 kg: 19 patients versus 3 patients p = 0.04). No significant differences were found for any other outcomes. CONCLUSION: Utilizing a flat-dose of G-CSF for patients after autoHSCT does not appear to negatively affect patient outcomes. Institutions may benefit from using the 300 mcg dose of G-CSF for multiple myeloma patients after autoHSCT.

Current state assessment survey of challenges of pharmacogenomics within oncology pharmacy practice.

PURPOSE: The goal of this survey was to identify opportunities for health systems to increase implementation and adoption of oncology-focused pharmacogenomics services. METHODS: An online survey assessing respondent demographics, baseline knowledge and training in pharmacogenomics, comfort level with pharmacogenomic data, and challenges of implementing clinical pharmacogenomic platforms was distributed to professional colleagues and over national oncology pharmacy listservs. Pharmacists were grouped based on their comfort level with pharmacogenomic data. Results were analyzed utilizing Pearson chi-square test. A p value of <0.05 was considered significant. RESULTS: A total of 84 participants from 58 cancer centers participated in the survey. Most participants were post-graduate year 2 trained and a majority reported being comfortable assessing oncology pharmacogenomic data. Respondents indicated that pharmacogenomics reported within the electronic medical record was the most common institutional process to support pharmacogenomics for oncology patients. Despite this, poor visibility of pharmacogenomics within the electronic medical record was the most challenging aspect of implementing a pharmacogenomic program. Additional challenges included lack of resources for pharmacogenomic programs, insurance denials for pharmacogenomic-driven testing and medication, and prolonged turnaround time of pharmacogenetic results. Length of practice, post-graduate year 2 residency training, institutions with pharmacist involvement on hematology/oncology molecular tumor board, and institutions where a pharmacist helped create local pharmacogenomic policies were significantly associated with respondents' comfortability in assessing pharmacogenomics. CONCLUSION: Oncology pharmacists reported substantial challenges in implementing a pharmacogenomic program. Future efforts to assist in developing pharmacogenomic efforts should focus on increasing pharmacist involvement, expanding education and training, and improving clinical decision support tools.

Severe Hypoglycemia Caused by Lenalidomide.

Lenalidomide is commonly used for multiple myeloma as either induction or maintenance therapy. The agent is associated with a host of adverse effects, but hypoglycemia has only been reported in one phase I trial in patients with solid tumors. We describe a 74-year-old woman who experienced grade 3 hypoglycemia (blood glucose level 35 mg/dl) likely related to lenalidomide. Her medical history was significant for refractory myeloma and type 2 diabetes mellitus. Lenalidomide was started as maintenance therapy following autologous bone marrow transplantation. Approximately 3 years later, she developed refractory hypoglycemia necessitating hospital admission despite stopping antihyperglycemic agents 4 weeks prior to admission. Lenalidomide was withheld during her admission and restarted 2 days prior to discharge. Work-up for causes of persistent hypoglycemia was negative, and her glucose levels improved over her 26-day hospitalization. She was readmitted approximately one month later for hypoglycemia, and lenalidomide was permanently discontinued. Again, work-up for causes of hypoglycemia was negative, and her glucose levels stabilized over her hospitalization. After discontinuation of lenalidomide, hypoglycemia did not recur, and within 1 year the patient required reinitiation of antihyperglycemic medications to control her glucose levels. Given the resolution of hypoglycemia with lenalidomide discontinuation and return of hyperglycemia after restarting the agent, it is likely that lenalidomide was the cause of the patient's hypoglycemia. Use of the Naranjo adverse drug reaction probability scale indicated a definite relationship (score of 9) between the patient's development of grade 3 hypoglycemia and lenalidomide therapy. Although this adverse drug reaction had been previously reported with lenalidomide during phase I trials in patients with solid tumors, only grade 1 or 2 hypoglycemia was reported in three patients. To our knowledge, this is the first reported case of grade 3 hypoglycemia caused by lenalidomide.

Moxifloxacin versus levofloxacin or ciprofloxacin prophylaxis in acute myeloid leukemia patients receiving chemotherapy.

PURPOSE: Patients receiving intensive chemotherapy regimens are at high risk for infectious complications due to prolonged neutropenia and hospital stay. Fluoroquinolone antibiotics, mainly levofloxacin and ciprofloxacin, are the mainstay of prophylactic therapy for these patients. There is limited data regarding the utilization of other quinolone antibiotics including moxifloxacin in this setting. METHODS: A retrospective chart review was completed comparing the use of prophylactic moxifloxacin to that of levofloxacin or ciprofloxacin during periods of prolonged neutropenia. Adult patients admitted to a community teaching hospital while receiving induction or reinduction chemotherapy for acute myeloid leukemia were included. RESULTS: One hundred and forty-one patients were included in this study. The two groups displayed slight heterogeneity: patients receiving moxifloxacin were approximately 10 years younger (54 vs. 64 years, p = 0.01), more likely to receive granulocyte colony stimulating factor (GCSF) (45 vs. 19%, p = 0.001), and neutropenic for a longer duration (23 vs. 19 days, p = 0.009). The incidence of febrile neutropenia (76 vs. 81%, RR 0.93, 95% CI 0.78-1.11, p = 0.42) and of documented infections (27 vs. 33%, RR 0.82, 95% CI 0.49-1.36, p = 0.44) was similar between those receiving moxifloxacin and levofloxacin/ciprofloxacin, respectively. Hospital readmission for an infectious issue within 30 days of hospital discharge (9 vs. 5%, p = 0.39) was also similar between groups as was the incidence of Clostridium difficile (9 vs. 9%, p = 0.96). CONCLUSIONS: Moxifloxacin may be an alternative to levofloxacin or ciprofloxacin in patients with a prolonged risk of febrile neutropenia requiring prophylaxis.