Unscheduled health care interactions in patients with multiple myeloma receiving T-cell redirection therapies.

Outcomes for patients with relapsed/refractory multiple myeloma (R/RMM) have dramatically improved after the development and now growing utilization of B-cell maturation antigen-targeted chimeric antigen receptor (CAR) T-cell therapy and bispecific antibody (BsAb) therapy. However, health care utilization as a quality-of-life metric in these growing populations has not been thoroughly evaluated. We performed a retrospective cohort study evaluating the frequency and cause of unscheduled health care interactions (UHIs) among patients with R/RMM responding to B-cell maturation antigen-targeted BsAb and CAR T-cell therapies (N = 46).

Patterns of CRS with teclistamab in relapsed/refractory multiple myeloma with or without prior T-cell redirection therapy.

Teclistamab (Tec) is a first-in-class BCMA × CD3 bispecific T-cell engager antibody approved for treating multiple myeloma progressing after at least 4 lines of therapy. The objective of this study was to evaluate the rate of cytokine release syndrome (CRS) in patients who were treated with commercial Tec and had prior exposure to other T-cell redirection therapies. A retrospective chart review was performed to identify patients who completed the Tec step-up dosing phase between November 2022 and November 2023.

Transition from Intravenous to Subcutaneous Daratumumab Formulation in Clinical Practice.

Introduction: Daratumumab is an anti-CD38 monoclonal antibody widely used for treating patients with newly diagnosed or relapsed/refractory multiple myeloma. The subcutaneous formulation of daratumumab was developed with the purpose of minimizing the treatment burden (to patients and health care system) associated with intravenous daratumumab. Given its recent approval, there is a knowledge gap regarding the best practices that should be instituted for safe administration of subcutaneous daratumumab.

Potentially actionable pharmacogenetic variants and symptom control medications in oncology.

Purpose: We estimated the prevalence of potentially actionable pharmacogenetic (PGx) variants related to symptom control medications (SCMs) based on institutional prescribing patterns and correlated presenting symptoms with SCM prescribing.

Methods: This was a retrospective study of adult ambulatory cancer patients undergoing electronic distress screening (EDS) within 90 days of intake to the cancer hospital. We estimated the proportion prescribed SCM(s) with PGx evidence within 90 days of intake.

Implications of Polymorphisms in the BCKDK and GATA-4 Gene Regions on Stable Warfarin Dose in African Americans.

VKORC1 and CYP2C9 genotypes explain less variability in warfarin dose requirements in African Americans compared with Europeans. Variants in BCKDK and GATA-4 gene regions, purported to regulate VKORC1 and CYP2C9 expression, have been shown to play an important role in warfarin dose requirements in Europeans and Asians, respectively. We sought to determine whether rs56314408 near BCKDK or GATA-4 rs2645400 influence warfarin dose requirements in 200 African Americans.

Examination of Metoprolol Pharmacokinetics and Pharmacodynamics Across CYP2D6 Genotype-Derived Activity Scores.

Recent CYP2D6 phenotype standardization efforts by CYP2D6 activity score (AS) are based on limited pharmacokinetic (PK) and pharmacodynamic (PD) data. Using data from two independent clinical trials of metoprolol, we compared metoprolol PK and PD across CYP2D6 AS with the goal of determining whether the PK and PD data support the new phenotype classification. S-metoprolol apparent oral clearance (CLo), adjusted for clinical factors, was correlated with CYP2D6 AS (P < 0.

Pharmacogenetics and tacrolimus administration in stem cell transplantation.

Tacrolimus is the gold standard immunosuppressant administered in solid organ and stem cell transplantation to avoid graft rejection post-transplant. Despite its widespread use, there is a large variation in response to therapy, likely due to high inter-individual pharmacokinetic variability. Therapeutic drug monitoring is employed to improve clinical response and reduce toxicity.

Safety and Cost Benefits of the Rapid Daratumumab Infusion Protocol.

Introduction: Daratumumab is approved for the treatment of multiple myeloma in both frontline and relapsed/refractory settings. Its major limitation is the long infusion time, especially with the first dose. Recent data demonstrated the feasibility of infusing daratumumab at an accelerated rate of 90 minutes starting from cycle 1 on day 15.

Pain Management Using Clinical Pharmacy Assessments With and Without Pharmacogenomics in an Oncology Palliative Medicine Clinic.

Purpose: Approximately 30% of patients with cancer who have pain have symptomatic improvement within 1 month using conventional pain management strategies. Engaging clinical pharmacists in palliative medicine (PM) and use of pharmacogenomic testing may improve cancer pain management.

Methods: Adult patients with cancer with uncontrolled pain had baseline assessments performed by PM providers using the Edmonton Symptom Assessment Scale.

Evaluation of CYP2C19 Genotype-Guided Voriconazole Prophylaxis After Allogeneic Hematopoietic Cell Transplant.

There is a high risk of voriconazole failure in those with subtherapeutic drug concentrations, which is more common in CYP2C19 (cytochrome P450 2C19) rapid/ultrarapid metabolizers (RMs/UMs). We evaluated CYP2C19 genotype-guided voriconazole dosing on drug concentrations and clinical outcomes in adult allogeneic hematopoietic cell transplant recipients. Poor (PMs), intermediate (IMs), and normal metabolizers (NMs) received voriconazole 200 mg twice daily; RMs/UMs received 300 mg twice daily.

Pharmacogenomics of osteonecrosis of the jaw.

Osteonecrosis of the jaw (ONJ) is a rare but serious drug induced adverse event, mainly associated with the use of antiresorptive medications, such as intravenous (IV) bisphosphonates (BPs) in cancer patients. In this review, we evaluated all the pharmacogenomic association studies for ONJ published up to December 2018. To date, two SNPs (CYP2C8 rs1934951 and RBMS3 rs17024608) were identified to be associated with ONJ by two genome-wide association studies (GWAS).

Effect of CYP3A4, CYP3A5, and ABCB1 Polymorphisms on Intravenous Tacrolimus Exposure and Adverse Events in Adult Allogeneic Stem Cell Transplant Patients.

Pharmacogenetics influences oral tacrolimus exposure; however, little data exist regarding i.v. tacrolimus.

Personalizing aromatase inhibitor therapy in patients with breast cancer.

Background: Aromatase inhibitors are the mainstay of therapy for patients with hormone receptor-positive breast cancer in both adjuvant and metastatic settings. Their use in clinical practice has been challenged by significant inter-individual variability in response and tolerability. Hence, the purpose of this paper is to provide a succinct review of the literature on the genetic factors contributing to this variability.

Optimization of Voriconazole Therapy for the Treatment of Invasive Fungal Infections in Adults.

Therapeutic concentrations of voriconazole in invasive fungal infections (IFIs) are ensured using a drug monitoring approach, which relies on attainment of steady-state pharmacokinetics. For voriconazole, time to reach steady state can vary from 5-7 days, not optimal for critically ill patients. We developed a population pharmacokinetic/pharmacodynamic model-based approach to predict doses that can maximize the net benefit (probability of efficacy-probability of adverse events) and ensure therapeutic concentrations, early on during treatment.

Multisite Investigation of Outcomes With Implementation of CYP2C19 Genotype-Guided Antiplatelet Therapy After Percutaneous Coronary Intervention.

Objectives: This multicenter pragmatic investigation assessed outcomes following clinical implementation of CYP2C19 genotype-guided antiplatelet therapy after percutaneous coronary intervention (PCI).

Background: CYP2C19 loss-of-function alleles impair clopidogrel effectiveness after PCI.

Methods: After clinical genotyping, each institution recommended alternative antiplatelet therapy (prasugrel, ticagrelor) in PCI patients with a loss-of-function allele.

SIRT1/HERC4 Locus Associated With Bisphosphonate-Induced Osteonecrosis of the Jaw: An Exome-Wide Association Analysis.

Osteonecrosis of the jaw (ONJ) is a rare, but serious drug side effect, mainly associated with the use of intravenous (iv) bisphosphonates (BPs). The purpose of this study was to identify genetic variants associated with ONJ in patients of European ancestry treated with iv BPs using whole-exome sequencing (WES). The WES phase 1 included 44 multiple myeloma patients (22 ONJ cases and 22 controls) and WES phase 2 included 17 ONJ patients with solid tumors.

Impact of the CYP2C19 genotype on voriconazole exposure in adults with invasive fungal infections.

Objectives: Voriconazole, a first-line agent for the treatment of invasive fungal infections (IFIs), is metabolized by CYP2C19. A significant proportion of patients fail to achieve therapeutic trough concentrations with standard weight-based voriconazole dosing, placing them at increased risk for treatment failure, which can be life threatening. We sought to test the association between the CYP2C19 genotype and subtherapeutic voriconazole concentrations in adults with IFIs.

Osteonecrosis of the Jaw in the United States Food and Drug Administration's Adverse Event Reporting System (FAERS).

Osteonecrosis of the jaw (ONJ) is a serious adverse drug event that was initially reported with intravenous bisphosphonates (BPs) and more recently with other classes of drugs such as receptor activator of NF-κB ligand (RANKL) inhibitor, antiangiogenic agents, and mammalian target of rapamycin (m-TOR) inhibitors. The purpose of this study is to analyze the ONJ cases and the associated drugs in the US Food and Drug Administration's adverse event reporting system (FAERS). The FAERS database was queried for the adverse drug events reported from the first quarter of 2010 to the first quarter of 2014.

Drug induced osteonecrosis of the jaw.

Despite the widespread use of bisphosphonates and their unequivocal efficacy for the treatment of various disease states, osteonecrosis of the jaw remains one of the most feared complications associated with their use. Current evidence, however, suggests that there is also a relationship between occurrence of osteonecrosis of the jaw and use of other classes of pharmacotherapies namely RANKL inhibitors as well as angiogenesis inhibitors. Although these drugs have different mechanisms of action than bisphosphonates, they all seem to interfere with the bone remodeling process i.