The Incidence and Health Care Resource Burden of the Myelodysplastic Syndromes in Patients in Whom First-Line Hypomethylating Agents Fail.

BACKGROUND: Although hypomethylating agents (HMAs) are effective and approved therapies for patients with myelodysplastic syndromes (MDS), many patients do not benefit from treatment, and nearly all ultimately stop responding to HMAs. The incidence and cost burden of HMA failure are unknown yet needed to appreciate the magnitude and significance of such failure. METHODS: We analyzed a de-identified dataset of over 5 million individuals with private health insurance in the U.S. to estimate MDS incidence, prevalence, and treatments. Based on MDS provider interviews, a conceptual model of MDS patient management was constructed to create a new, claims-relevant and drug development-relevant definition of HMA treatment failure. This algorithm was used to define resource encumbrance of MDS patients in whom HMA treatment failed. RESULTS: We estimated an MDS incidence rate of ∼70 cases per 100,000 enrollees per year and a prevalence of 155 cases per 100,000 enrollees. The proportion of MDS patients receiving HMA treatment was low (∼3%), and treatment was typically initiated within 1 year of the first MDS claim. Notably, HMA-treated individuals were older and had more comorbidities than the overall MDS cohort. Total health care costs of managing MDS patients after HMA failure were high (∼$77,000 during the first 6 months) and were driven primarily by non-pharmacy costs. CONCLUSION: This study quantifies for the first time the burden of significant unmet need in caring for MDS patients following HMA treatment failure. The Oncologist 2017;22:379-385Implications for Practice: U.S.-based treatment patterns among MDS patients demonstrate the significant clinical, financial, and health care burden associated with HMA failure and call for active therapies for this patient population.

Phase I trial of UNBS5162, a novel naphthalimide in patients with advanced solid tumors or lymphoma.

OBJECTIVES: UNBS5162 is a novel naphthalimide that binds to DNA by intercalation and suppresses CXCL chemokine elaboration. A Phase I study of UNBS5162 was conducted to establish pharmacokinetics (PK), maximum tolerated dose (MTD), dose-limiting toxicity, safety and anti-tumor activity in patients with advanced solid tumors or lymphoma. METHODS: UNBS5162 was administered in a 3 + 3 dose escalation scheme by intravenous infusion over 1 h weekly for 3 weeks of a 4-week cycle. Safety, serial serum PK and tolerability were captured throughout the study. Response Evaluation Criteria in Solid Tumors was utilized every 2 cycles to assess for anti-tumor response. RESULTS: Twenty-four patients with metastatic carcinoma and 1 patient with lymphoma were treated at eight dose levels (18-234 mg/m(2)). All patients were evaluable for tolerability and toxicity. Grade 3 toxicities include nausea (n = 1), fatigue (n = 1) and anorexia (n = 1). Prolongation of QTc [Hodges] was observed in 6 cases (Gr 1 = 2; Gr 2 = 2; Gr 3 = 2). C(max) and area under the curve increased linearly with dose with a t(1/2) of 30-60 min. 16 patients completed 2 cycles of therapy, all with pharmacodynamics at 8 weeks. CONCLUSIONS: The MTD or dose-limiting toxicity for UNBS5162 was not reached due to the magnitude of QTc prolongation at the highest dose of 234 mg/m(2)/week that led to study termination.

Biomarker Pursuit: Keeping Current With Novel Biomarkers in Hematology/Oncology.

In the popular biomarker-focused session at JADPRO Live 2022, presenters paired biomarkers with tumor types for which their expression is most commonly used to determine targeted therapy, identified key assays used to measure common biomarkers, and reviewed recommendations and guidelines for biomarker testing.

The Prevention of COVID-19 in High-Risk Patients Using Tixagevimab-Cilgavimab (Evusheld): Real-World Experience at a Large Academic Center.

BACKGROUND: Coronavirus disease 2019 (COVID-19) is associated with increased morbidity and mortality among immunocompromised patients. Tixagevimab-cilgavimab (Tix-Cil) is a combination of 2 monoclonal antibodies approved for the prevention of COVID-19 complications in this high-risk group. METHODS: We retrospectively reviewed the charts of patients who received Tix-Cil during the Omicron variant period (January 17 to April 23, 2022), with a follow-up period until May 24, 2022. We collected data about patient underlying comorbidities and post Tix-Cil COVID-19 infections, deaths, and hospitalizations. RESULTS: There were 463 patients with a median age of 68 years, of which 51% were male, 79% White, 13.2% Hispanic, 1.7% Black/African American, and 5.8% identified as Other. A total of 18% had undergone a solid organ transplantation or hematopoietic stem cell transplantation. Only 6/98 (6.1%) had severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) detected by polymerase chain reaction (PCR) at a median 48 days (interquartile range [IQR] 27.5, 69) follow-up. Forty-two patients (9.1%) were hospitalized, and 4 (0.9%) died, but none were attributed to COVID-19 or Tix-Cil. One hospitalized patient had an incidental, asymptomatic, positive SARS-CoV 2 by PCR. The median days from Tix-Cil administration to non-COVID-19-related hospitalization and death were 30 (IQR 17, 55) and 53 (IQR 18, 91), respectively. CONCLUSION: Tix-Cil provides protection against COVID-19 complications in immunocompromised patients with suboptimal immune responses to vaccines.

Moving beyond ruxolitinib failure in myelofibrosis: evolving strategies for second line therapy.

INTRODUCTION: Ruxolitinib has been the cornerstone of pharmacologic therapy for myelofibrosis for over a decade. However, the last several years have witnessed the regulatory approval of other Janus kinase (JAK) inhibitors for myelofibrosis, i.e. fedratinib, pacritinib, and US approval of momelotinib is widely anticipated in 2023. AREAS COVERED: Due to the multifaceted clinical presentation of myelofibrosis, a watertight definition of ruxolitinib failure has remained elusive, as "progression" on ruxolitinib can take many forms and management is highly nuanced. Yet, the availability of other JAK inhibitors and potential future availability of non-JAK inhibitor agents for myelofibrosis make a consensus on management of ruxolitinib failure critically important. This consensus paper summarizes a discussion between multiple academic and community physician experts, a pharmacist and an advanced practice provider around the issues to be considered for the optimal care of patients with myelofibrosis whose disease is refractory to or does not respond adequately to ruxolitinib, or who exhibit intolerance to ruxolitinib. EXPERT OPINION: The panel identified several areas of consensus, as well as some areas where more data to inform evidence-based practice are needed. In some situations, maintaining ruxolitinib while adding another agent, e.g. to address anemia, is appropriate, whereas in others, switching to a different drug has merit.

Survey of patients and physicians on shared decision-making in treatment selection in relapsed/refractory multiple myeloma.

Shared decision-making (SDM) is a key component of patient-centered healthcare. SDM is particularly pertinent in the relapsed and/or refractory multiple myeloma (RRMM) setting, in which numerous treatment options can present challenges for identifying optimal care. However, few studies have assessed the extent and relevance of SDM and patient-centered communication (PCC) in RRMM. To describe treatment decision-making patterns between physicians and patients in the RRMM setting, we conducted online surveys of patients and physicians in the USA to compare their perspectives on the process of treatment decision-making. We analyzed the surveys descriptively. Two hundred hematologists/oncologists and 200 patients with RRMM receiving second-line (n = 89), third-line (n = 65), and fourth-line (n = 46) therapy participated. Top treatment goals for physicians and patients included extending overall survival (among 76% and 83% of physicians and patients, respectively) and progression-free survival (among 54% and 77% of physicians and patients, respectively), regardless of the number of prior relapses. Thirty percent of physicians believed patients preferred a shared approach to treatment decision-making, while 40% of patients reported most often preferring a shared role in treatment decision-making. One-fourth of patients most often preferred physicians to make the final treatment decision after seriously considering their opinion. Thirty-two percent of physicians and 16% of patients recalled ≥3 treatment options presented at first relapse. Efficacy was a primary treatment goal for patients and physicians. Discrepancies in their perceptions during RRMM treatment decision-making exist, indicating that communication tools are needed to facilitate SDM and PCC.

Shared decision-making (SDM) is an important facet of patient-centered healthcare. Multiple myeloma (MM) is a cancer of the bone marrow that can return (relapse) after treatment. SDM may be especially pertinent for relapsed MM as there is no uniform standard of care and treatment selection can be complex. Few studies have examined the extent and relevance of SDM and patient-centered communication (PCC) in this relapsed and/or refractory (RRMM) setting. We conducted online surveys of 200 patients who had received 1­3 previous therapies and 200 physicians to compare treatment decision-making patterns in RRMM in the USA. Both physicians and patients felt that extending patient survival was a top treatment goal, regardless of the number of prior relapses. A lower percentage of physicians believed patients preferred a shared approach to treatment decision-making than patients who reported preferring such a shared role. Twice as many physicians than patients recalled ≥3 treatment options presented at first relapse. In conclusion, while improving survival was an important treatment goal for physicians and patients, there are discrepancies in physician and patient perceptions during RRMM treatment decision-making. Thus, communication tools are needed to facilitate SDM and PCC.

Transplantation Referral Patterns for Patients with Newly Diagnosed Higher-Risk Myelodysplastic Syndromes and Acute Myeloid Leukemia at Academic and Community Sites in the Connect® Myeloid Disease Registry: Potential Barriers to Care.

Hematopoietic stem cell transplantation (HCT) is indicated for patients with higher-risk (HR) myelodysplastic syndromes (MDS) and acute myeloid leukemia (AML). Age, performance status, patient frailty, comorbidities, and nonclinical factors (eg, cost, distance to site) are all recognized as important clinical factors that can influence HCT referral patterns and patient outcomes; however, the proportion of eligible patients referred for HCT in routine clinical practice is largely unknown. This study aimed to assess patterns of consideration for HCT among patients with HR-MDS and AML enrolled in the Connect® Myeloid Disease Registry at community/government (CO/GOV)- or academic (AC)-based sites, as well as to identify factors associated with rates of transplantation referral. We assessed patterns of consideration for and completion of HCT in patients with HR-MDS and AML enrolled between December 12, 2013, and March 6, 2020, in the Connect Myeloid Disease Registry at 164 CO/GOV and AC sites. Registry sites recorded whether patients were considered for transplantation at baseline and at each follow-up visit. The following answers were possible: "considered potentially eligible," "not considered potentially eligible," or "not assessed." Sites also recorded whether patients subsequently underwent HCT at each follow-up visit. Rates of consideration for HCT between CO/GOV and AC sites were compared using multivariable logistic regression analysis with covariates for age and comorbidity. Among the 778 patients with HR-MDS or AML enrolled in the Connect Myeloid Disease Registry, patients at CO/GOV sites were less likely to be considered potentially eligible for HCT than patients at AC sites (27.9% versus 43.9%; P < .0001). Multivariable logistic regression analysis with factors for age (<65 versus ≥65 years) and ACE-27 comorbidity grade (<2 versus ≥2) showed that patients at CO/GOV sites were significantly less likely than those at AC sites to be considered potentially eligible for HCT (odds ratio, 1.6, 95% confidence interval, 1.1 to 2.4; P = .0155). Among patients considered eligible for HCT, 45.1% (65 of 144) of those at CO/GOV sites and 35.7% (41 of 115) of those at AC sites underwent transplantation (P = .12). Approximately one-half of all patients at CO/GOV (50.1%) and AC (45.4%) sites were not considered potentially eligible for HCT; the most common reasons were age at CO/GOV sites (71.5%) and comorbidities at AC sites (52.1%). Across all sites, 17.4% of patients were reported as not assessed (and thus not considered) for HCT by their treating physician (20.7% at CO/GOV sites and 10.7% at AC sites; P = .0005). These findings suggest that many patients with HR-MDS and AML who may be candidates for HCT are not receiving assessment or consideration for transplantation in clinical practice. In addition, treatment at CO/GOV sites and age remain significant barriers to ensuring that all potentially eligible patients are assessed for HCT.

Counselling and adverse event management for patients with myelodysplastic syndromes undergoing azacitidine therapy: a practice standard for Canadian nurses.

Azacitidine (5-azacytidine, VIDAZA) is a disease-modifying agent that improves survival, reduces transfusion dependence, and reduces progression to acute myeloid leukemia in patients with higher risk myelodysplastic syndromes. Azacitidine injection is associated with characteristic adverse events (AEs) that must be managed in order for patients to stay on therapy and achieve optimal therapeutic outcomes. These AEs include injection-site reactions, cytopenias, and gastrointestinal effects. Oncology nurses are uniquely positioned to provide patient support and counselling, thereby helping patients and their families set clear expectations for azacitidine therapy. This article presents a nursing standard designed to support Canadian oncology nurses in the key areas of counselling for patients initiating and continuing azacitidine, as well as nursing strategies for prevention and management of azacitidine-associated AEs. Many of the general principles discussed in this nursing standard can be applied broadly to many diseases and treatments.

Biomarker Jeopardy.

In the popular Biomarker Jeopardy session, Sandra E. Kurtin, PhD, ANP-C, AOCN®, Alyssa Henglefelt, PharmD, BCOP, and Haleigh Mistry, MS, PA-C, paired biomarkers with tumor types for which their expression is most commonly used to determine targeted therapy, identified key assays used to measure common biomarkers, and discussed guidelines for biomarker testing.

Implementation of an Oral Antineoplastic Therapy Program: Results From a Pilot Project.

BACKGROUND: The Oncology Care Model requires implementation of processes to reduce urgent care (UC), emergency department (ED), and hospital visits for patients on antineoplastic therapies, including oral antineoplastic agents. OBJECTIVES: The purpose of this project was to develop, implement, and initially evaluate an oral antineoplastic therapy program (OAP) and an oncology antineoplastic nurse navigator (OANN) role aimed at reducing UC, ED, and hospital visits. METHODS: This pilot project used a descriptive correlational design to analyze the impact of the novel role of the OANN on UC, ED, and hospital visits. FINDINGS: The OANN engaged 1,095 patients between January 1, 2019, and December 31, 2020. A reduction in UC, ED, and hospital visits was noted between 2019 and 2020 for patients followed by the OANN and enrolled in the OAP. Patients who were contacted by the OANN three or more times after starting their oral antineoplastic agent were less likely to be seen in UC or the ED or to be hospitalized. The novel role of the OANN within the overall OAP provided a significant benefit in reducing UC and ED visits and hospitalization for patients enrolled in the program.