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Friday, February 3, 2023

Supportive Care Services for Patients With Myeloproliferative Neoplasms

​By Sarah DiGiulio

Myeloproliferative neoplasms are a group of blood cancers that can lead to significant symptom burden and reduced quality of life. “But limited studies have focused on distress," noted Rushil V. Patel, MD, a hematology/oncology fellow at Levine Cancer Institute.

In oncology, distress refers to any negative experience arising from physical, psychological, social, religious, or spiritual factors that impact how patients with cancer cope with their illness. Higher levels of distress (from any of these factors) have been linked with worse outcomes overall, including more clinician visits, emergency department visits, and longer hospital stays.

Guidelines from the National Comprehensive Cancer Network recommend that patients with cancer be screened for distress and those reporting a mid-level of distress (4 or higher on the NCCN 10-point scale) be referred to supportive services (J Natl Compr Canc Netw 2019; https://doi.org/10.6004/jnccn.2019.0048). “However, patients with elevated distress do not always get referred to appropriate services," Patel said.

That's why Patel and his colleagues set off to evaluate patients with these blood cancers and answer these questions. How much distress do patients experience? Do patients who experience distress get referred to supportive services? And how many patients experiencing distress go on to be hospitalized?

The data showed that, despite consensus recommendations that patients with distress should be evaluated by supportive services, most were not. Social work was most frequently utilized among patients with distress who did to part in supportive services. Patients with polycythemia vera and myelofibrosis were more likely to report distress compared with patients with essential thrombocythemia.

“There is little known about the incidence of distress in patients with myeloproliferative neoplasms," said Srdan Verstovsek, MD, PhD, a hematologist-oncologist in the Department of Leukemia at the University of Texas MD Anderson Cancer Center, adding that a lot is known, however, about the poor quality of life these patients live with.

“This particular report is eye-opening for us all. The complexity of life and distress patients experience is huge according to this report and certainly requires further work by other myeloproliferative neoplasm specialists in order to understand the problem well and develop proper tools to address patients' needs." Verstovsek was not involved in the study. The research was presented at the 2022 ASH Annual Meeting (Abstract 2313).

Study Details

The study analyzed data from 141 patients 18 years or older diagnosed with myelofibrosis, polycythemia vera, or essential thrombocythemia and had been seen by a clinician (for at least one visit) between January 1, 2017, and June 30, 2021, at Levine Cancer Institute and completed an electronic distress survey. The surveys included sociodemographic questions and patient-reported outcomes: distress level, physical symptoms, screening for depression and anxiety, daily function, social support, and emotional and spiritual concerns.

The primary objective was to assess patients scoring a 4 or higher on the distress screening if they saw a supportive care provider (including someone in either psychiatry, social work, psychology, chaplaincy, palliative care, or integrative oncology) within 6 months of screening. The analysis also looked at the proportions of automated referrals based on system triggers, unplanned hospitalizations, and emergency room visits.

The data showed the following details:

  • 75 patients (53%) reported significant distress, of which 44 (59%) were within 3 months of diagnosis
  • 25 patients (33%) expressed significant distress and were evaluated by one of the services of interest within 6 months of screening
  • 38 patients were automatically referred for supportive services; 15 of those patients (39%) were evaluated within 6 months
  • Patients reporting distress had significantly more emergency department visits than patients without distress (15% vs. 0%), but not more unplanned hospitalizations (16% vs 6%).

“I was disturbed by the findings," Verstovsek noted. “While for patients with myelofibrosis, one can perhaps accept the findings as a consequence of relatively aggressive neoplasm, similar findings in patients with polycythemia vera were truly shocking."

He added that similar studies across a broader spectrum of cancer care settings are needed to understand the scope of the problem. A limitation of this study is that it was a single-institution study. “This report calls for action between myeloproliferative neoplasm experts to try to help our patients in distress in a better way with better understanding of their needs," Verstovsek said.

Patel added that the analysis is limited by not having longitudinal data to see how distress changes throughout the course of someone's illness. “For instance, 59 percent of distressed patients were within 3 months of diagnosis. Was their distress related to symptoms and/or establishing care with a hematologist or oncologist? We don't know unless we reassess their distress," he concluded.​

Sarah DiGiulio is a contributing writer. 

Tuesday, January 24, 2023

Insured Cancer Patients Continue to Face Barriers to Medically Necessary Treatment, New Report Warns

A new report from a national cancer nonprofit warns that delays and red tape jeopardize patients' access to lifesaving cancer care—even when they have high-quality health insurance.

The report, “Vital Access: How Policymakers Can Streamline the Cancer Care Journey," offers concrete solutions that would ensure the policies that govern our health insurance system are able to keep up with the pace of new cancer treatments and diagnostics. It was produced by The Leukemia & Lymphoma Society (LLS) and Manatt Health, a leading consulting firm with deep expertise in health policy.

“In many cases, the healthcare system we have today has allowed roadblocks to patients' health to persist, rather than opening doors to the treatment they need," said Lucy Culp, Executive Director of State Government Affairs at LLS and co-author of the report. “There's a better way."

Patients' odds of surviving cancer often hinge on their ability to access specialists who can evaluate, diagnose and treat their particular type of cancer as quickly as possible. But too often, patients encounter barriers that prevent them from accessing that care and benefiting from incredible advancements in cancer treatment.

Some blood cancer survival rates have more than doubled over the last 50 years. At the same time, insurance coverage in the U.S. has improved dramatically in recent years, with the uninsured rate reaching an all-time low of 8 percent in 2022, according to the federal government.

However, the new report's findings suggest better treatments and greater insurance coverage still aren't enough to help some cancer patients, who face insurance denials, limited provider options, and complicated appeals processes when insurance claims are denied.

“The good news is, there are tools available to plans, providers and regulators to address many of these continued gaps for individuals that have insurance but are unable to access care," said Alex Morin, Manatt Health Director and co-author of the report.  “But it's clear that we are not taking advantage of them to their fullest potential and as a result, patients and families continue to suffer."

The report was informed by interviews with more than two dozen cancer patients and family members who encountered roadblocks to care. The study, for example, cites the case of J.J. Duncan, a California mother whose son's plan wouldn't cover cutting-edge cancer care that was only available to him in another state. Another patient, based in New Jersey, had to pay on his own for doctor-ordered follow-up imaging because of complicated and time-consuming appeals processes with his insurer. “This experience has forever changed the way I look at health insurance," Duncan said in the report.

The report offers specific recommendations for state and federal policymakers as they work toward developing insurance regulations that advance a more equitable system of care. Chief among them: ensuring access within narrow insurance networks – which are increasingly common in both commercial health insurance and Medicaid – as well as eliminating red tape, streamlining prior authorization and appeals processes, and making it easier for patients to get care out-of-state.​

Tuesday, December 13, 2022

Hispanic Patients With AML Have Distinct Genetic Makeup & Worse Outcomes

​By Dibash Kumar Das, PhD

The Hispanic population is the largest minority group in the U.S., accounting for approximately 19 percent of the total population. The term Hispanic/Latino refers to people of Cuban, Puerto Rican, Mexican, South/Central American, or other Spanish-speaking cultures, regardless of race. Unfortunately, U.S. Hispanics experience many different health disparities, including cancer health disparities, resulting in poor survival outcomes and a reduced quality of life.

To better comprehend disparities in Hispanic patients with acute myeloid leukemia (AML), Guzman and colleagues characterized and compared clinical features, mutational landscape, and disease outcomes of AML patients from Mexico (Mex) and Hispanic AML patients living in U.S. (A-Hisp) and to non-Hispanic White (A-NHW) patients. The study was presented at the 2022 ASH Annual Meeting and Exposition (Abstract 4945).

The researchers investigated molecular features and outcomes of adult AML patients in four cohorts:

  • Cohort 1 (Mex): 48 AML patients diagnosed and treated with anthracycline and cytarabine combination (90%) at the Hospital General de Mexico.
  • Cohort 2 (A-Hisp, A-NHW): 48 adult AML patients who self-identified as Hispanic and 1,496 non-Hispanic White patients similarly treated as cohort 1 on frontline Alliance protocols.
  • Cohorts 3 & 4: Additional reported Hispanic cohorts in the U.S. and large international cohorts for validation of the identified molecular and clinical features.

Mutational status of 55 protein-coding genes in addition to the main fusion gene rearrangements at time of diagnosis were determined using targeted NGS platforms.

The findings revealed that median age at diagnosis for cohorts 1 and 2 was younger than reported for AML, 38 years old (15-86) for cohort 1 versus 45 years old (17-83) for cohort 2. Somatic mutations were detected at similar rates for Hispanic populations: 96 percent of patients in cohort 1 and 94 percent of A-Hisp patients in cohort 2. FLT3 was the most prevalent mutation among the cohorts: (Mex 29%, A-Hisp 33%, A-NHW 42%, p=0.654). Other prevalent mutations included: CEBPA (Mex 21%, A-Hisp 15%, A-NHW 13%, p=0.214), TET2 (Mex 19%, A-Hisp 8%, A-NHW 16%, p=0.322), DNMT3A (Mex 19%, A-Hisp 18%, A-NHW 24%,p=0.5498), RUNX1 (Mex 15%, A-Hisp 0%, A-NHW 12%, p<0.001), and NPM1 (Mex 12%, A-Hisp 29%, A-NHW 35%, P=0.002). Fusion genes were discovered in 21 percent of patients.

Although some commonalities were discovered in the genetic alterations between the two Hispanic cohorts, the median overall survival (OS) was worse for the Mexican cohort (9 months) compared to the OS for cohort 2 (A-Hisp 15mo, A-NHW 14mo). Strikingly, CEBPA-mutated AML was overrepresented in both cohort 1 and A-Hisp (cohort 2). The prevalence of mutated NPM1 was the most notable difference between the two Hispanic cohorts (Mex vs. A-Hisp); NPM1 was higher in the U.S. A-Hisp dataset, similar to what is described in other international cohorts for de novo AML. The molecular differences were validated in the two additional international cohorts.

Oncology Times connected with senior author, Monica L. Guzman, PhD, for additional insights into the study. She is Associate Professor of Pharmacology in the Department of Medicine at Weill Medical College of Cornell University.
 
Oncology Times: How can the findings of this study potentially improve clinical decision-making?
Guzman: “Identifying the molecular abnormalities in AML in Hispanic populations (ancestry-based, as opposed to self-reported) will provide significant insight into the differences and similarities that characterize AML in the Hispanic population compared with non-Hispanic White populations. Furthermore, if there are unique molecular features within Hispanic subgroups (based on ancestry), this could result in improved diagnostic assay development and eventually access to adequate treatments for Hispanic patients especially those in low-income countries. Furthermore, this will potentially lead to clinical trials designed and tailored to improve the treatment of AML in Hispanic populations."

Oncology Times: As indicated in the study, the root cause of these disparities is likely multifactorial. Are there any state or national programs that are working to improve the disparities in Hispanic patients with AML by promoting awareness, removing barriers to health care access, and ultimately improve health outcomes in this population?
Guzman: “Many groups are working on ways to remove barriers, including the American Society of Hematology; that is why we are so excited about this pilot study, to begin to understand what those barriers are. Comparing the biology and outcomes between Hispanic/Latinx patients in their home countries and Hispanic/Latinx patients living in the U.S. will enable us to unveil such barriers. We are currently extending our study to additional countries through collaborations, such as Bolivia, Colombia, and Brazil."

Oncology Times: What future research may be beneficial to determine other component causes of health disparities in outcomes among Hispanic patients with AML versus non-Hispanic White patients?
Guzman: “The next steps include looking into the role of certain inherited mutations and other predisposing factors that may affect clinical outcomes, in addition to other genetic factors that can affect specific drug responses."

Dibash Kumar Das is a contributing writer.​

Tuesday, December 13, 2022

Electronic Tablet-Based Approach Helps Tailor Patient Discussions & Treatment

​By Catlin Nalley

A recent study demonstrated the feasibility of using an electronic tablet-based process to collect  patient goals, decision-making preferences, and top concerns at the time of treatment decisions among older patients with acute myeloid leukemia, according to findings at the 2022 American Society of Hematology Annual Meeting and Exposition (Abstract 3548).

“Incorporating patient goals, preferences, and concerns at the time of treatment decision-making is important yet challenging to do in a busy clinic," noted study author Omer Jamy, MD, Assistant Professor in the Division of Hematology and Oncology, Department of Medicine, University of Alabama at Birmingham. “A systematic approach using electronic tablets at the treatment decision visit may support both documenting the patients goals, preferences, and concerns, and potentially facilitate their incorporation into the shared treatment decision making conversation."

Jamy and colleagues conducted a feasibility study to assess the utility of an electronic tablet-based questionnaire at a treatment decision-making time point in patients with acute myeloid leukemia (AML).

This multi-institutional, prospective, single-arm intervention study sought to determine the feasibility of implementing an electronic tablet-based questionnaire for patients with AML, prior to seeing the physician at a treatment decision-making time point, according to Jamy. Patients were recruited from three academic cancer centers.

Before seeing their physician, each patient completed baseline surveys via an electronic tablet. The surveys included beliefs about curability of their cancer, goals of care, decision making preferences, top concerns, and a modified geriatric assessment (mGA) screening tool, the study author explained.

“The mGA includes four domains: age, activities of daily living (ADLs), instrumental ADLs, and comorbidities. Modified geriatric assessment survey results along with history of falls was used to create the Frailty Index (FI)," they outlined in their abstract. “All questionnaire results were immediately displayed on a dashboard for the physician to refer to during the clinical visit."

The study enrolled 77 patients with a median age of 71 years. Fifty were female (64.9%), 67 White (87.0%), and 33 were college educated (42.9%). Additionally, the study authors noted that 43 (56.6%) were former or current smokers, 52 (72.7%) were interested in clinical trial participation, and 50 (64.9%) did not have an advanced directive.

Jamy and colleagues reported the following FI results for 76 patients: 28 (36.8%) fit, 25 (32.9%) intermediate fit, and 23 (30.3%) frail. One patient did not complete the mGA. “At baseline, 57 (74%) believed their cancer was curable. Seventy-six (98.7%) agreed a goal of care was to live longer, 77 (100.0%) agreed a goal was to feel better, and 75 (97.4%) agreed a goal was to get rid of all of the cancer," the data showed. Forty-one (53.9%) patients expressed a desire to share responsibility for deciding what treatment was best with their physician, 16 (21.0%) preferred to make the final selection, and 19 (25.0%) wanted to leave decisions regarding treatment to their physician.

Participating patients selected up to five responses from a list of common concerns. “Although 36 (46.8%) indicated they had no concerns at the time, 24 (32.2%) selected “Do I understand my treatment options?", 22 (28.6%) selected “Am I making the right treatment decision?", 13 (16.9%) selected “I am worried about the costs of my care", and 12 (15.6%) selected “How do I manage my family activities and my treatment schedule," the study authors said.

When discussing the key takeaways from their research, Jamy noted that this pilot study demonstrated the feasibility of collecting patient goals, decision-making preferences, and top concerns at the time of a treatment decision in older patients with AML.

“Technology was used to support shared decision-making at the point of care. Patients were able to complete brief surveys that elicited their goals of care, expectations of treatment outcomes, decision-making preferences, and their top concerns," he told Oncology Times. “Each question asked in this study provided the clinician with information to inform the treatment discussion. Furthermore, we found that completing the surveys, without workflow disruption, was feasible from both the patient and provider perspective."

This study shows that a simple electronic tool provides valuable insight into patient understanding of disease to better tailor patient-provider discussion and treatment decision-making, according to Jamy. “A summary presented to the provider at the point of care facilitates a focused discussion whereby the patient and provider may plan treatment together.

“Furthermore, technology can also support the ongoing discussions throughout treatment as patient preferences may also change over time and clinicians need to revisit these throughout the cancer care continuum," he concluded. “Further studies to help integrate and implement such tools in real-world settings are needed."​

Catlin Nalley is a contributing writer.

Tuesday, December 13, 2022

TP53-Aberrant MDS & AML Treatment Patients With Inferior Clinical Outcomes

​By Dibash Kumar Das, PhD

TP53 gene mutations are detected in up to 20 percent of patients with de novo myelodysplastic syndromes (MDS) or acute myeloid leukemia (AML) and up to 40 percent of patients with therapy-related disease. There are also no FDA-approved targeted therapies available for TP53- aberrant MDS/AML.

Previously, Shyam A. Patel, MD, PhD revealed understandings into the reasons underlying the adverse clinical outcomes for TP53-aberrant MDS and AML to improve rational therapeutic design (Leuk Lymphoma 2021: https://doi.org/10.1080/10428194.2021.1957869). Now, the team has discovered that TP53-aberrant MDS and AML comprise a prognostically heterogeneous group of patients with inferior clinical outcomes. The study was presented at the 2022 ASH Annual Meeting and Exposition (Abstract 2792).

The researchers identified 63 patients (median age: 69.8) from the UMass Chan Leukemia Registry harboring one or more aberrations in TP53 and with either MDS or AML between 2011 and 2022. Patients were stratified by the presence or absence of multi-hit status and/or TP53 variant allele frequency (VAF) >50 percent. Multi-hit status was defined as per the 2022 International Consensus Classification (ICC): two or more distinct TP53 mutations with VAF ≥ 10 percent, or a single TP53 mutation plus one of the following abnormalities: 1) del(17p13.1), 2) TP53 VAF >50 percent, 3) copy-neutral loss-of-heterozygosity, or 4) any complex karyotype. Monoallelic status was defined as non-multi-hit.

Fifty-eight patients met the 2022 ICC classification for myeloid neoplasm with mutated TP53. Patients with multi-hit TP53-mutant AML had significantly shorter survival (median 46 days) versus patients with monoallelic TP53-mutant MDS, multi-hit TP53-mutant MDS, and monoallelic TP53-mutant AML (median overall survival (OS) 440 days vs. 437 days vs. 440 days, respectively).

Patients with multi-hit status MDS or AML (n=41) were sub-stratified based on TP53 VAF. OS for patients with MDS with VAF ≤ 50 percent and VAF > 50 percent was similar (median 376 days vs. 435 days, respectively), yet the highest risk subgroup appears to be AML with TP53 VAF > 50 percent (median 43 days).

Of the 63 patients, 19 percent underwent allogeneic hematopoietic cell transplant (allo-HCT). OS was significantly improved with allo-HCT. Three of the 12 allo-HCT beneficiaries achieved MRD-free remission lasting beyond 1,000 days. In these long-term survivors with TP53-mutant MDS or AML, the VAF was ≤ 10 percent.

In efforts to gain further clarity on the prognostic profile of TP53 mutations of MDS and AML, Oncology Times spoke with first author, Shyam A. Patel, MD, PhD, Assistant Professor of Hematology/Oncology at UMass Chan Medical School and UMass Memorial Medical Center.
 
Oncology Times: What are some of the current treatment gaps/challenges for patients with TP53-aberrant MDS and AML?
Patel: “One of the major treatment gaps/challenges is suboptimal long-term disease control. First-line therapy can often result in remission, but genomic residual disease often triggers relapse within a short time frame. As UMass, we have found that high mutant TP53 gene dosage predicts low durability of remission, but we do not have mechanistic insight yet. Another gap/challenge is that certain frontline therapies may lead to selection and expansion of these TP53-mutant clones, with subsequent changes in the subclonal composition that confer more aggressive behavior. Yet another major gap/challenge is the lack of superior precision therapies for this subset of patients."
 
Oncology Times: How can the findings of this study improve clinical decision-making?
Patel: “The findings can improve clinical decision-making by informing selection of frontline therapy based on a classical disease labels (MDS vs. AML) and based on mutant TP53 gene dosage (monoallelic vs. multi-hit). The allele state or hit status, in turn, may be reflected by variant allele frequency, gross structural status of the 17p13 locus, and/or copy number variation.

“At the current time, there is some debate as to whether morphology plays a major role in this genetically defined subgroup of patients, and our findings suggest that some MDS and AML subgroups (all except multi-hit TP53-mutant AML) have similar outcomes. Clinical decision-making may need to be different for multi-hit TP53-mutant AML since outcomes are significantly worse."
 
Oncology Times: The study found that patients with multi-hit TP53-mutant AML had significantly shorter survival versus patients with monoallelic TP53-mutant MDS, multi-hit TP53-mutant MDS, and monoallelic TP53-mutant AML. What are some potential factors for why we did not see more uniform outcomes?
Patel: “This an important question for which we do not have a definitive answer. The reason for not seeing more uniform outcomes may be related to the more aggressive biology of multi-hit TP53-mutant AML compared to the other subgroups. Regarding the MDS versus AML prognostic discrimination, by the time a patient's bone marrow or peripheral blood blast percentage exceeds 20 percent, it can be very challenging to gain disease control. Another factor could be that the mutational burden is higher in AML compared to MDS. Although the blast progression from MDS to AML may be a first-degree function of time, the blasts in AML may also have inferior genomic integrity compared to those in MDS. Regarding the monoallelic versus multi-hit prognostic discrimination, the reason for not seeing more uniform outcomes may be that the multi-hit state renders p53 completely inactive, leading to resistance to chemotherapy."
 
Oncology Times: What are some limitations of the current analysis that you would like to address in future studies?
Patel: “One limitation of the current analysis is that we do not have a deep understanding of the clonal composition of these clinical subgroups of TP53-aberrant MDS and AML. In the future, it is worth addressing stem cell-based factors when making clinical decisions. For example, attempts at 'cure' may need to target the malignant self-renewing compartment, while attempts at disease control (without cure) may only need to target progenitors or mature blasts. At the current time, management is partly tailored to each patient's goals of care (curative intent vs. mere control), but future studies should attempt to identify a targeted therapy has 'curative intent' for all patients."

Dibash Kumar Das is a contributing writer.​