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.

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.

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.

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.

Improving patient understanding and outcomes in myelodysplastic syndromes - An animated patient guide to MDS with visual formats of learning.

Objectives: Patient education resources that address barriers to health literacy to improve understanding and outcomes in myelodysplastic syndromes (MDS) are limited. The aim of this study was to evaluate the impact and outcomes benefits of An Animated Patient's Guide to Myelodysplastic Syndromes (MDS) cancer educational modules (which includes the 'You and MDS' website and YouTube hosted resources) related to MDS education, awareness, understanding and health outcomes. Methods: This was a retrospective study of learner feedback, metrics, and utilization data from July 2018 to August 2021. We evaluated audience reach (number of visit sessions, unique visitors, page views) and calculated top views by media type (animation, expert video, patient video, and slide show) and top retention videos from the modules. We also assessed the educational impact and utilization through learner feedback surveys. Results: During the study period, 'You and MDS' had 233,743 views worldwide of which 104,214 were unique visitors and 78,161 (or 76% unique visitors) were from the United States. Of these, 61% were patients; 29% family members or caregivers; 5% were healthcare providers and 5% represented other groups. Most popular topics viewed among the animations were "Understanding Myelodysplastic Syndromes (MDS)" (40,219 views), "Managing and Treating MDS" (19,240 views), "Understanding Erythropoiesis" (17,564 views.) The most popular expert videos viewed were "What is iron overload, and how it is treated?" (20,310 views), "How serious a cancer is MDS? What is the prognosis for MDS?" (8,327 views), "What is MDS?" (3,157 views). Of participants who completed the online feedback survey, ≥ 95% reported improved knowledge gains and commitments to change. Conclusions: MDS patients using 'You and MDS - An Animated Patient's Guide to MDS' and its visual formats of learning represented a wide U.S. and global learner audience. This MDS educational resource had a significant impact on improved understanding among patients, families, and caregivers. Continued efforts should be made to provide patient-effective resources that address health literacy, improve patient understanding, and address educational needs that respond to the concerns of patients to achieve better quality of life and improved health outcomes in MDS.

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.

Biomarker Jeopardy.

The popular Biomarker Jeopardy session returned this year at JADPRO Live 2020. Sandra E. Kurtin, PhD, ANP-C, AOCN®, led the session, and was joined by Alyssa Henglefelt, PharmD, BCOP, and Allyson Price, PA-C. Using a Jeopardy format, they identified specific biomarkers while discussing targeted therapies and class effects APs should be aware of.

Optimizing Treatment of Chronic Lymphocytic Leukemia.

During JADPRO Live Virtual 2020, Sandra Kurtin, PhD, ANP-C, AOCN®, described personalization of the treatment of chronic lymphocytic leukemia (CLL) using molecular attributes of the disease, as well as patient characteristics. Dr. Kurtin discussed front-line treatment in previously untreated patients, treatment for relapsed or refractory CLL, and how to prevent, mitigate, and manage adverse events in order to optimize treatment.

Real-world diagnostic testing patterns for assessment of ring sideroblasts and SF3B1 mutations in patients with newly diagnosed lower-risk myelodysplastic syndromes.

INTRODUCTION: The presence of ring sideroblasts (RS) and mutation of the SF3B1 gene are diagnostic of lower-risk (LR) myelodysplastic syndromes (MDS) and are correlated with favorable outcomes. However, information on testing and reporting in community-based clinical settings is scarce. This study from the Connect® MDS/AML Disease Registry aimed to compare the frequency of RS and SF3B1 reporting for patients with LR-MDS, before and after publication of the 2016 World Health Organization (WHO) MDS classification criteria. METHODS: Ring sideroblasts assessment and molecular testing data were collected from patients with LR-MDS at enrollment in the Registry. Patients enrolled between December 2013 and the data cutoff of March 2020 were included in this analysis. RESULTS: Among 489 patients with LR-MDS, 434 (88.8%) underwent RS assessment; 190 were assessed prior to the 2016 WHO guidelines (Cohort A), and 244 after (Cohort B). In Cohort A, 87 (45.8%) patients had RS identified; 29 (33.3%) patients had RS < 15%, none of whom underwent molecular testing for SF3B1. In Cohort B, 96 (39.3%) patients had RS identified; 31 (32.3%) patients had < 15% RS, with 13 undergoing molecular testing of which 10 were assessed for SF3B1. CONCLUSIONS: In the Connect® MDS/AML Registry, only 32% of patients with <15% RS underwent SF3B1 testing after the publication of the WHO 2016 classification criteria. There was no change in RS assessment frequency before and after publication, despite the potential impact on diagnostic subtyping and therapy selection, suggesting an unmet need for education to increase testing rates for SF3B1 mutations.

Clinical Trial Design and Drug Approval in Oncology: A Primer for the Advanced Practitioner in Oncology.

Evidenced-based practice requires timely and accurate integration of scientific advances. This presents a challenge for the oncology clinician given the robust pace of scientific discovery and the increasing number of new drug approvals and expanded indications for previously approved drugs. All currently available antineoplastic therapies have been developed through the clinical trials process. Advanced practitioners (APs) in oncology are often involved in the conduct of clinical trials as primary investigators, sub-investigators, study coordinators, or in the delivery and monitoring of care to patients enrolled in these trials. A prerequisite to evidenced-based practice is understanding how clinical trials are conducted and how to critically analyze published results of studies leading to U.S. Food & Drug Administration approval. Any AP involved in the clinical management and supportive care of patients receiving antineoplastic therapies should be able to critically review published data to glean findings that warrant a change in practice. The goals of this manuscript are to summarize key elements of the clinical trial process for oncology drug development and approval in the United States and to provide a primer for the interpretation of clinical data.

Diagnostic and molecular testing patterns in patients with newly diagnosed acute myeloid leukemia in the Connect® MDS/AML Disease Registry.

Diagnostic and molecular genetic testing are key in advancing the treatment of acute myeloid leukemia (AML), yet little is known about testing patterns outside of clinical trials, especially in older patients. We analyzed diagnostic and molecular testing patterns over time in 565 patients aged ≥ 55 years with newly diagnosed AML enrolled in the Connect® MDS/AML Disease Registry (NCT01688011) in the United States. Diagnostic data were recorded at enrolment and compared with published guidelines. The percentage of bone marrow blasts was reported for 82.1% of patients, and cellularity was the most commonly reported bone marrow morphological feature. Flow cytometry, karyotyping, molecular testing, and fluorescence in situ hybridization were performed in 98.8%, 95.4%, 75.9%, and 75.7% of patients, respectively. Molecular testing was done more frequently at academic than community/government sites (84.3% vs 70.2%; P < .001). Enrolment to the Registry after 2016 was significantly associated with molecular testing at academic sites (odds ratio [OR] 2.59; P = .023) and at community/government sites (OR 4.85; P < .001) in logistic regression analyses. Better understanding of practice patterns may identify unmet needs and inform institutional protocols regarding the diagnosis of patients with AML.

Integrating Touchscreen-Based Geriatric Assessment and Frailty Screening for Adults With Multiple Myeloma to Drive Personalized Treatment Decisions.

PURPOSE: Geriatric assessment (GA) results predict toxicity/survival in older adults, yet GA is not routinely used in care for patients with multiple myeloma (MM). We tested a tablet-based modified GA (mGA) providing real-time results to clinicians. METHODS: One hundred sixty-five patients with MM aged ≥ 65 years facing a treatment decision from 4 sites completed a tablet-based mGA with Katz Activities of Daily Living (ADL), Lawton Instrumental ADL, Charlson Comorbidity Index, and variables from the Cancer and Aging Research Group's Chemotherapy Toxicity Calculator. Providers reviewed the assessment results at the treatment visit. RESULTS: Patients were white (72%; n = 86), mean age was 72 years (range, 65-85 years), and averaged 7.71 minutes (range, 2-17 minutes) for survey completion. Providers averaged 3.2 minutes (range, 1-10 minutes) to review mGA results. Using International Myeloma Working Group frailty score, patients were fit (39%; n = 64), intermediate fit (33%; n = 55), or frail (28%; n = 46). Providers selected more aggressive treatments in 16.3% of patients and decreased treatment intensity in 34% of patients; treatment intensification was more common for fit patients and milder treatments for frail patients (χ2 = 20.02; P < .0001). Transplant eligibility significantly correlated with fit status and transplant ineligibility with frail status (P = .004). Outcomes on 144 patients 3 months post study visit showed 19.4% (n = 28) had grade ≥ 3 hematologic toxicities, 38.9% (n = 56) had dose modifications, and 18% (n = 26) had early therapy cessation. CONCLUSION: Limited patient time required for survey completion and provider time for results review show mGA can be easily incorporated into clinical workflow. Real-time mGA results indicating fit/frailty status influenced treatment decisions.

Implementation of a pharmacy-managed program for the transition of chemotherapy to the outpatient setting.

PURPOSE: Implementation of a pharmacy-managed program for the transition of chemotherapy to the outpatient setting is described. SUMMARY: The University of Arizona Cancer Center and Banner-University Medical Center Tucson are affiliated not-for-profit academic medical centers in Tucson, Arizona, whose facilities include a hospital and ambulatory care clinics that maintain 3 outpatient infusion centers. The cancer center pharmacy currently employs 25 pharmacists, with 4 clinical pharmacists serving both the inpatient and outpatient treatment sites. A multidisciplinary team of staff members was assembled to address the transition of chemotherapy from inpatient to outpatient that included physicians, ambulatory clinical oncology pharmacists, finance, social workers, pharmacy staff, nursing staff, and information technology. The program was initiated in May 2014, with a 2-year postimplementation evaluation of our transition of chemotherapy to the outpatient setting. Chemotherapy order sets were developed in our electronic medical record for transitioning rituximab to the outpatient setting for inpatient chemotherapy orders as well as transitioning leukemia, lymphoma, and solid tumor chemotherapy regimens to be administered in the outpatient setting. Eighteen rituximab-containing regimens and 14 chemotherapy protocols were switched to the outpatient setting, with numerous variants of these regimens also created for outpatient only administration. The realized savings for high-cost chemotherapy transitioned to the outpatient setting with rituximab and clofarabine was $1,902,890. Over 747 inpatient bed days were saved, with an approximated cost savings to the health system of $1,402,866, with a cumulative cost savings to our health system of $3,305,756. CONCLUSION: This model for transitioning chemotherapy from the hospital to the outpatient setting enhanced access to care, decreased bed utilization in the hospital, and improved clinical and financial metrics.

Emerging immune targets for the treatment of multiple myeloma.

We reviewed emerging immune strategies for multiple myeloma (MM) therapy excluding US FDA approved drugs. In relapsed refractory MM, isatuximab (anti-CD38) monotherapy achieved overall response (OR) of 24%. Other monoclonal antibodies that have shown efficacy in combination therapy include siltuximab (OR: 66%), indatuximab (OR: 78%), isatuximab (OR: 64.5%), pembrolizumab (OR: 60%), bevacizumab (OR: 70%), dacetuzumab (OR: 39%) and lorvotuzumab (OR: 56.4%). No OR was observed with monotherapy using BI-505, siltuximab, bevacizumab, AVE-1642, figitumumab, atacicept, milatuzumab, dacetuzumab, lucatumumab, IPH2101, lorvotuzumab, BT062 and nivolumab. We included seven clinical trials on chimeric antigen receptor (CAR) T cells. CAR T-cell targets include BCMA, CD19, KLC and CD138. A recent experience of CAR T-cell (B-cell maturation antigen) therapy in advanced MM has shown global response of 100%. The future of monoclonal antibodies and adoptive T cells for MM treatment seems promising.

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.

Multiple Myeloma Mentorship: Bridging Communication and Educational Gaps.

BACKGROUND: The 2014 Multiple Myeloma (MM) Mentorship Program provided a focused, interactive, peer-to-peer educational experience, including updates in MM, for 10 mentees that led to advanced clinical educator status. OBJECTIVES: The objective of the program was (a) to improve mentees' knowledge, competency, confidence, and level of performance in the management of MM and (b) to build speaking expertise. METHODS: From May 2014 to March 2015, 10 mentees were educated on MM with a structured serial learning curriculum. Mentees then presented slide decks, and modular activities were opened to a national audience of professionals. Pre- and post-test surveys were compiled, and a RealIndex® composite score was calculated. FINDINGS: Gains were measured across the curriculum in learning domains of knowledge, confidence, and practice strategy. Pre-/post-test scores show that the mentorship cohort's average scores on knowledge, confidence, and performance were higher compared to the national program.