A pharmacogenomic (PGx) panel will be performed to test for genetic variations in genes related to drug response.

Patients undergoing hematopoietic stem cell transplantation will be genotyped and supportive care therapies tailored to identified drug-gene pairs and guideline recommendations

Pharmacogenomic-guided supportive care

Justin R Arnall, PharmD

Hematopoietic cell transplantation (HCT) is the only curative treatment modality for many hematologic malignancies. Morbidity and mortality rates have declined drastically over the years, secondary to improvements in both transplant techniques and pharmacotherapies, including immunosuppressants, anti-infectives, analgesics and other supportive care medications. Despite advances in patient care, toxicities associated with HCT (e.g., graft-versus-host disease (GVHD), infection, pain, anxiety, depression, mucositis, nausea/vomiting) continue to pose challenges in patient care and have a significant impact on quality of life. (QOL). A recent study demonstrated subjects randomized to intensive supportive care had a clinically significant improvement in their QOL during hospitalization and up to 3 months post-transplant compared to those receiving standard care.

Further follow up evaluations have evaluated the impact of focused palliative care/symptom management on QOL metrics - inclusive of Edmonton Symptom Assessment surveys (ESAS). In other malignant settings, i.e. solid tumor, ESAS has been noted as an effective measure of symptoms control and the utilization of this assessment is linked to positive outcomes. The American Society of Clinical Oncology (ASCO) has designated QOL as the second most relevant metric for post-transplant patient care behind survival, making the optimization of supportive care pharmacotherapy a clinically relevant subject to investigate. Pharmacogenetics (PGx) uses an individual's genetic factors, such as single nucleotide polymorphisms (SNPs), to personalize therapy or dose selection. SNPs encode drug-metabolizing enzymes, transporters, and targets that can significantly impact drug efficacy and toxicity. With the growing complexity of both antineoplastics and supportive care, oncologists have less time to manage each subject's myriad of supportive care concerns by trial and error. Suboptimal management of symptoms compromises potential benefits from cancer therapy, disrupts clinic workflow, increases emergency room visits, and affects both patient satisfaction and reimbursement. Genetic variation is well documented across the human genome and affects a subject's response to medications regarding efficacy and toxicity. The genome is quickly becoming a pragmatic tool that can assist oncologists and other providers in optimizing supportive care for subjects with cancer.

The investigators hypothesize that the implementation of a pharmacist-driven precision medicine service guided by HCT clinical pharmacists and Specialty Pharmacy pharmacists using preemptive pharmacogenomic (PGx) testing will identify drug-gene interactions relevant to the supportive care of HCT subjects. This approach to care may improve symptom management and QOL as interpreted via ESAS in adult HCT subjects treated at our institution. With the experience of past studies and a customized genetic panel, the investigators will genotype subjects prior to transplant and identify actionable drug-gene pairs and utilize these to direct supportive therapies. To date no studies have highlighted the significance of incorporating preemptive PGx testing to personalize therapy selection and dosing into the management of adult HCT subjects as a means of improving QOL and symptom management. The primary aim is to estimate the frequency of subjects undergoing PGx testing who receive at least one drug/dose selection or modification based on their test results during the study period (from admission for HCT to HCT D100). Secondarily the investigators will measure improvement in aggregate and individual scores on the ESAS survey and will further use the ESAS in its totality to assess the impact of PGx-guided care as compared to pre-implementation/non-PGx driven strategies through aggregate ESAS scores, individual ESAS scores, and differences between HCT admission (or baseline) and HCT Day 30 scores before and after the intervening program. In the outpatient setting the investigators will utilize planned medication reconciliation (with PGx guidance) by Specialty Pharmacy Service pharmacists to adhere to PGx-recommendations and capture insight into the implementation of this program to share with other practitioners. The implementation of this study will personalize pharmacotherapy, improve symptom management and QOL in adult HCT subjects treated at our institution, and offer guidance globally in supporting the role of the pharmacist in pharmacogenomics (PGx) and management of HCT subjects.

This will be a prospective, pre/post interventional, single arm study

Pharmacogenomic-Guided Supportive Care in Hematopoietic Cell Transplantation

A Prospective Interventional Trial of Pharmacogenomic-Guided Supportive Care in Hematopoietic Cell Transplantation

All data and records generated during this study will be kept confidential in accordance with Institutional policies on subject privacy and HIPAA and that the investigator and other site personnel will not use such data and records for any purpose other than conducting the study. We do not anticipate any breach of confidentiality as no records will be shared with any personnel outside the research team. All medical information will be recorded and stored in a database. The database will exist on a password protected secured server. Medical records data will be abstracted by the Research Designee. All records will be kept confidential.

The primary objective is to estimate the frequency of subjects undergoing PGx testing who receive at least one drug/dose selection or modification based on their test results during the study period

Determine if PGx-guided supportive care is associated with changes in symptom management following HCT compared to control data attained from subjects not consenting to PGx testing, as assessed by individual and aggregate Edmonton Symptom Assessment Scale (ESAS) scores as well as their changes in ESAS scores (ESAS being an 11-point symptoms assessment with low scores associated with low symptom burden and the high scores associated with significant burden)

Describe longitudinal changes in individual and aggregate Edmonton Symptom Assessment Scale (ESAS) scores as indicative of QOL (ESAS being an 11-point symptoms assessment with low scores associated with low symptom burden and the high scores associated with significant burden)

Among the PGx-guided supportive care subjects, investigators will assess the type and frequency of actionable genetic polymorphisms observed in the evaluable population and in the subset that received a drug and/or dose selection/modification based on PGx results

Wake Forest University Health Sciences

Neoplasms

Blood and Lymph Conditions

All Conditions

Immune System Diseases

Heart and Blood Diseases

Symptoms and General Pathology

Rare Diseases

Leukemia

Leukemia, Myeloid

Leukemia, Lymphoid

Multiple Myeloma

Neoplasms, Plasma Cell

Chronic Disease

Hematologic Neoplasms

Leukemia, Lymphocytic, Chronic, B-Cell

Leukemia, Myelogenous, Chronic, BCR-ABL Positive

Multiple Chronic Conditions

Neoplasms by Histologic Type

Hematologic Diseases

Hemostatic Disorders

Blood Coagulation Disorders

Vascular Diseases

Paraproteinemias

Blood Protein Disorders

Hemorrhagic Disorders

Lymphoproliferative Disorders

Immunoproliferative Disorders

Lymphatic Diseases

Leukemia, B-Cell

Disease Attributes

Myeloproliferative Disorders

Bone Marrow Diseases

Myeloid Leukemia

Chronic Graft Versus Host Disease

Chronic Lymphocytic Leukemia

Chronic Myeloid Leukemia

Chronic Myeloproliferative Disorders

The Pharmacist Coordinated care Oncology Model includes patient self-reported symptoms and medication adherence, comprehensive medication review(s) and intentional communication between oncology and community pharmacists.

Participants will complete a patient-reported outcome measure for their oral anticancer agent at two timepoints over 2 months, to assess patient symptoms and adherence to their oral anticancer agent.

Patient-reported outcome measure

Following the first patient-reported outcome measure, participants will be contacted by the community pharmacist for a Comprehensive Medication Review (CMR) for their chronic medications. A follow-up CMR will take place after the second patient-reported outcome measure.

Comprehensive Medication Review

Throughout the study, the oncology and community pharmacists will communicate about medications through the electronic medical record.

Pharmacist communication

Justin Gatwood, PhD

Katie Gatwood, PharmD

The objective of this study is to improve medication, symptom, and disease management of patients with hematological malignancies and multiple chronic conditions (2 or more conditions in addition to cancer) through care coordination between pharmacists working in oncology practices and those working in primary care or community practices (Pharmacists Coordinated care Oncology Model \[PCOM\]).

This is a pilot study in which the investigators will examine the association between outcome measures, but the study design and sample size are insufficient to quantify the impact of OAA initiation or OAA adherence on adherence to chronic medications. This pilot study and data analyses are being done in preparation for a larger, controlled study.

Oral Adherence in Hematological Oncology Agents and Impact on Comorbid Therapy Adherence

PDC is a common medication adherence metric, and assesses the ratio of number of days the patient is supplied with oral anticancer agent, from the time of initiation until 6 months later, to the total number of days during that period. Data from the electronic medical record for dose changes will be aligned with the refill data to calculate a dose-adjusted PDC.

PDCs for medications for select chronic diseases will be calculated for the 6 months before and after oral anticancer agent initiation

The oncology-specific patient-reported outcome measure is to be completed at 2 and 6 weeks after oral anticancer agent initiation. This measure assesses the percent of patients who complete this tool at both time points.

Proportion of enrolled subjects completing the initial and follow-up CMRs with the community pharmacist

The patient-reported outcome measure is scored within one day after it is completed by the subject and is routed to the oncology pharmacist to review the results. The number of measures that are reviewed within 1 day of receipt will be assessed at 2 weeks and at 6 weeks.

The number of CMRs where note was routed to oncology pharmacist out of total number of completed CMRs, assessed at 2 weeks and at 6 weeks.

The number of CMR notes reviewed by the oncology pharmacist out of the total number of completed CMRs, assessed at 2 weeks and at 6 weeks.

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization	Link
Pharmacogenomic-Guided Supportive Care in Hematopoietic Cell Transplantation	NCT04727827	Hematopoietic C... Oncology	Pharmacogenomic...	18 Years -	Wake Forest University Health Sciences
Oral Adherence in Hematological Oncology Agents and Impact on Comorbid Therapy Adherence	NCT04663100	Chronic Myeloid... Chronic Lymphoc... Multiple Myelom... Multiple Chroni...	Patient-reporte... Comprehensive M... Pharmacist comm...	18 Years -	University of Tennessee

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