Yet, at times like these, the moment seems less than miraculous. As the scientific underpinnings of oncology advance well past the frontiers of
what I might have imagined possible when I graduated from medical school 32 years ago, the ability to ensure that all patients and families benefit consistently and equitably remains as distant as it has any time in the past. No matter how far knowledge and innovation can take us, we remain beholden to systems that lack the plasticity to grapple with this time of immense change. So, as we revel in the potential of all the ways in which we have advanced well past the limitations of prior decades, we remain beholden to seemingly intransigent barriers based on ossified systems of care.

Following its passage in March 2010, the Affordable Care Act promised to change so much,
but expanded coverage has yet to translate fully into equitable access to the kinds of care that represent the hallmarks of the precision medicine revolution. As we embrace a transformational pipeline of innovative, life-altering therapeutics, we continue to struggle to create a sustainable model of how best to pay for these therapeutics. Inasmuch as advanced technology, such as chimeric antigen receptor T-cells, portend the ability to effectively treat patients with relapsed and refractory cancers, we struggle to create the requisite care networks and payment models to ensure that patients who need these treatments actually receive them.

It is easy to become deluded that there are simple fixes or magical remedies for the challenges that we face in making the full breadth of cancer innovation available to the patients and families that need them most. There is no single program, piece of legislation, CMS demonstration project, or “shiny new object” that will cure the ills of our system. I have heard the word “value” bandied about in careless ways that distracts from the hard work and intradisciplinary collaboration that will be essential to fully define and subsequently realize a value-centered system of cancer care.

™, we see both the future of what can be, and the prosaic
bumps in the road that will make a full realization of that future difficult. Mary Caffrey provides a
summary of a recent webinar, “Genomic Testing Creates Opportunities for Collaboration Between
Academic Centers, Private Sector.” This conversation covered potential steps in fostering and advancing more effective cancer care that is built upon the foundations of genomic testing and precision medicine delivery. We also examine what a more effective ecosystem for delivering care to cancer patients might look like in our review of the updated standards for an Oncology Medical Home between the Community Oncology Alliance and the American Society of Clinical Oncology. At the same time, the limits of our current system, including limitations in coverage for the care of patients with blood cancers and our continued struggle with the creation of meaningful, actionable metrics for assessing oncology physician performance remind us of the ways in which our system struggles to adapt to this period of hyperdynamic change.

I remain an optimist that the lives of cancer patients and their families will continue to evolve in ways that will bring better outcomes, better patient experience, and more sustainable care costs. I do not, however, underestimate the extraordinary amount of work, collaboration, blood, toil, tears and sweat that it will take to get us there. Wherever we are, we will be there as a community of the community, trying to find the best path forward, a struggle in which we will strive, “to seek, to find, and not to yield.” 

Articles

FROM THE EDITORS

"No matter where you go, there you are." 
Buckaroo Banzai

From the Editor-in-Chief: Shiny New Objects Within a Struggling System

Quality measurement in federal health care programs has been around since at least 2007, when CMS introduced the Physician Quality Reporting System (PQRS) for providers caring for Medicare beneficiaries. The program continued to evolve, and it eventually became part of CMS’ Merit-Based Incentive System (MIPS), CMS’ first attempt to integrate several different incentive-based programs under one umbrella, including PQRS and meaningful use.

 The goal of MIPS is to optimize patient care by utilizing financial incentives to encourage providers to deliver high-quality, cost-efficient care.

Although the program’s intentions are good, stakeholders have shared criticism of potential structural flaws in MIPS; these flaws may serve to prevent widespread adoption and discourage commercial payers from fully embracing the program and similar risk arrangements structured around value-based care. CMS is attempting to rectify many of these critiques about MIPS by introducing MIPS Value Pathways (MVPs).

 MVPs are disease state- or specialty-specific subsets of measures and activities that consolidate core concepts across the 4 separate performance
areas in MIPS.

A closer look at what CMS is attempting to do with these specialty-specific MVPs, as well as ways they can be made more successful than MIPS, may provide some useful insight for
clinicians and payers.

MVPs Strive to Eliminate Cherry-Picking of Quality Measures and Improvement Activities

One concern with the MIPS program is that it provides clinicians  with full autonomy to select the quality measures and improvement activities that they want to report. The 4 performance areas—quality, improvement activities, promoting interoperability, and cost—are very siloed, rather than integrated. In its current format, clinicians can select quality measures where their performance is high, even if the measures are not relevant to the core activities of their area of specialty. Furthermore, clinicians can select from a full list of improvement activities for their 90-day attestation, even if the activity has been fully adopted at the practice for several years. In such cases, CMS is not achieving the intent of the program by stretching clinicians to adopt new, innovative solutions to drive improved patient care.

The new MVPs attempt to eliminate these silos and target the issue of cherry-picking, along with some other fundamental flaws in the MIPS program. To achieve this, CMS has indicated that the
new MVPs promote targeted concepts across the 4 MIPS categories, making the program more meaningful and valuable by having clinicians report on measures and activities specific to their areas of practice. Different specialties will have a core set of measures relating to their areas of care that clinicians will be obligated to choose from, rather than selecting their top-performing measures from the full menu of quality measures and improvement activities. CMS’ vision is to create a core set of measures and activities that are complementary and drive improvements in patient care, targeting specific disease areas or specialty care.


Factors That May Inhibit MVPs’ Success


While creating a framework for more specialty-specific and meaningful participation in the MIPS program through MVPs is positive movement in the right direction, many issues will apparently still need to be addressed before widespread adoption is likely to occur and for the program to become successful and viable for the long term. These include the following:

NEED FOR CLARITY ON SCORING METHODOLOGY FOR MVP VS. TRADITIONAL MIPS PARTICIPANTS.

 CMS recently published the 2022 Proposed Rule containing additional criteria for MVPs. Contained in the Proposed Rule, CMS further described the potential scoring methodology. CMS has proposed to reduce the reporting burden for MVP participants by requiring 4 quality measures from a MVP-specific measure set instead of the 6 required by traditional MIPS that can be selected across an inventory of approximately 200 measures. This will certainly help reduce “cherry picking” of measures where clinicians select measures based on performance, rather than relevance to the area of medicine for that specialty clinician. However, there is no timeline for when the transition to MVPs will be required and not optional. It seems that there should be scoring considerations to incentivize specialty clinicians to adopt MVPs to even the playing field with those who choose to continue participating in traditional MIPS.

Additionally, for some specialties, no measures are applicable in certain categories. For example, no specific episode-based cost measures are appropriate for medical oncology. There is a single, broad total per capita cost measure, which is more relevant to primary care services provided to Medicare patients. If CMS determines that this cost measure is not appropriate, how would CMS reweight the points for the cost category to make sure it is still fair across the board? Simply put, many questions around how scoring will occur are still open.

OPTIONAL PARTICIPATION WILL PERPETUATE ADOPTION LAG. 

CMS is currently planning a gentle, phased-in rollout for MVPs, which ultimately may make it optional for many clinicians. This may slow adoption of the program and create difficulties for the incentives and penalties associated with the MVP. With low participation, the necessary funds will be lacking to pay incentives, since funding for the incentives is supposed to come from penalties paid by poor performers. But with low participation, very few practices will be penalized, providing very limited funds for incentives. This is the same situation as exists in MIPS, where the incentive payment has been hovering around 1%. Performers in the top 80% to 90% are earning an adjustment of only 0.9% to 1.2%. These practices have invested significant dollars to implement MIPS, so many feel it has not been worth the investment.

DELAYED INFORMATION FROM CMS DOES NOT PROVIDE ACTIONABLE DATA FOR PARTICIPANTS

. One of the biggest issues practices have articulated regarding MIPS—which will likely also be an issue with MVPs—is that the program is retrospective and provides no actionable data. Practices are just now seeing their MIPS positive or negative adjustments from their participation in 2019, representing a 2-year delay. Additionally, CMS does not provide actionable feedback throughout the year that would enable clinicians or practices to better understand areas for improvement. 

Consequently, no ongoing feedback or identification of patients is included in the practice’s MIPS scoring (specifically, their cost measure and patients who will be attributed to them), so they are unable to effectively manage their patients’ overall cost of care nor to implement processes during the performance year that would lead to effective improvements in quality care and cost efficiencies.

Without some kind of timely data sharing that provides meaningful information—meaningful enough for practices to adjust the care they provide—MIPS Value Pathways will most likely struggle the same way MIPS has. 


Since the new MVPs are still in the developmental stage, CMS has opportunities to address issues that could help ensure long-term success. First and foremost, CMS must provide better access to data for clinicians, technology vendors, and measure developers.

Clinicians need timely data to make positive, effective change throughout the performance year, so information is meaningful, actionable, and current. Technology vendors need CMS to supply data and funding, as they are currently burdened to develop solutions and incorporate data sets to provide feedback to clinicians. However, there is no money in MIPS submissions due to low participation. Measure developers face similar problems, with no access to Medicare data that would enable them to better develop measures that leverage information from multiple sources. A positive approach would be for CMS to make available claims data and other data sources that developers could then incorporate into more meaningful quality measures. 

Over the years, CMS has outsourced certain responsibilities for measure and registry development and support to third parties, including registries, state societies, specialty societies, and organizations like McKesson. However, these endeavors are costly, and there is no incentive to develop or support these measures when there is no revenue in the program for these activities. By incentivizing—ie, funding measure development or providing resources to support the measures once they are established—CMS could ensure that experts stay involved and perhaps even encourage more collaboration across key stakeholders to develop meaningful measures.

The new MVPs should also align with other programs, such as the Oncology Care Model (OCM),

 By ensuring that the MVPs are developed such that they align with other regulatory programs and initiatives, the same core messages can be used across the practice to support quality care. For example, the measures in the OCM could align with the measures CMS selects for the oncology MVP core set of measures. Having this alignment would likely drive incorporation of these core measures and activities as part of managed care payer arrangements.

By aligning under some core values or initiatives from these programs, practices can take certain
activities across the entire patient population and monitor their success for all patients. This
encourages measuring things that matter, enabling clinicians to “buy in” on a core set of services or activities that are applicable for all of their patients, regardless of a patient’s participation in a particular program. This alignment facilitates development of processes and procedures across the care team that focus on the core areas. These activities—including advance care planning, depression screening, and pain management, to name just a few—are essentially the services the practice will provide for every patient, as they are part of the right clinical approach and are also critical components of high-quality, comprehensive cancer care.

Not only should the new MVPs align across programs, they should also align components
within the quality measure sets that drive improved patient-centered care and emphasize initiatives known to be associated with reduced health care costs and improved outcomes in oncology. To be successful, the MVPs should be outcomes-focused, and not just broad-based process measures.

McKesson and The US Oncology Network Collaborate on a Patient-Centric MVP

McKesson, a leader in advancing value-based cancer care, has collaborated with The US Oncology Network (The Network), a network of independent, physician-owned community practices, to develop an oncology-specific MVP; it has been submitted to CMS for consideration to be included in the future MIPS framework. The Network represents more than 10,000 oncology physicians, nurses, clinicians, and cancer care specialists nationwide, and the organization was instrumental in gathering input for the proposal.

This MVP addresses legitimate ways to improve specialty care and the patient experience, while reducing costs, when possible, through a more integrated approach than the current MIPS framework. It offers opportunities to improve the quality of care and value for cancer patients, as well as measures and activities that foster care coordination across care teams. This ensures patient-centric, personalized care that aligns with patients’ goals and wishes. 

Unlike the existing MIPS program, the quality measures and improvement activities in McKesson’s MVP are meaningful to oncology. They measure items that matter to the oncology clinician, rather than holding them accountable for management of health care concerns better managed by other specialists, such as diabetes or other chronic conditions. The quality measures focus on components of care that prioritize patient involvement and the patient’s voice, which are critical to optimizing patient-centered oncology care. Many of the improvement activities stress shared decision-making in treatment choices, a core tenet of value-based care. Patient involvement is emphasized in such activities as development of a care plan and advance care planning initiatives; this fosters meaningful discussions with patients about their values and goals for treatment and end-of-life care. 

With a strong emphasis on incorporating the patient voice to drive improvements in oncology care, McKesson’s MVP includes 2 patient-reported outcome measures: one to measure improvement in pain management, and a second that utilizes a comprehensive, oncology-specific patient survey to assess various aspects of cancer care and the patient experience. Gauging patients’ attitudes about their care and experiences paves the way to employ an exciting new area of research called mindsets—core assumptions about the nature and workings of things that can influence the mental and physical health of patients with cancer, potentially improving their outcomes.

 The MVP provides a strong framework for implementing targeted psychological interventions from the care team that aim to instill more positive mindsets in patients to drive better outcomes.

Through similar measure selection, care plan development, and integration of the patient experience survey—all components of care that help improve quality and cost—McKesson’s MVP aligns with existing and proposed programs in the Center for Medicare and Medicaid Innovation (CMMI), such as the OCM, Oncology Care First, and the RO Model. By providing a similar framework and areas of focus as existing CMMI programs, the MVP serves as a vehicle to incrementally phase clinicians into alternative payment models and to create a sense of alignment to reinforce key areas critical to oncology care. Focusing on the core areas of care enables the care team to provide an enhanced suite of services under the value-based care umbrella, treating all patients equally without thinking about whether a patient is participating in a particular program.

Managed care will find many positives in McKesson’s patient-centric MPV, as it is designed to drive and support the delicate balance of improved quality with lower costs that value-based care requires, all while ensuring that the patient’s voice is strongly heard.


Commercial payers will be keeping a close eye on what happens with the new oncology-specific MVPs. Because many questions still exist around whether quality measures actually have a meaningful impact on patient outcomes and reducing costs, payers have been slower to truly integrate quality measurements into value-based care arrangements. All stakeholders, including payers, are anxiously waiting to see how these programs perform and whether they meet hoped-for expectations. Payers tend to follow the government’s lead, but until many of the details are clearly defined within the regulatory programs and they are running  smoothly, payers will most likely take a wait-and-see approach. They will also be looking for clear-cut evidence that these programs are effective in supporting value-based care before confidently moving forward. 


Erin Crum, MPH, is the director of quality measurement strategy for McKesson.



1. Fiedler M, Gronniger T, Ginsburg PB, Patel KK, Adler L, Darling M. Congress should replace Medicare’s Merit-Based Incentive Payment System. Health Aff Blog. February 26, 2018. Accessed July 20, 2021. https://www.healthaffairs.org/do/10.1377/hblog20180222.35120/full/

2. MIPS Value Pathways (MVPs). CMS/Quality Payment Program. Accessed July 20, 2021. https://qpp.cms.gov/mips/mips-value-pathways

3. Oncology Care Model. CMS. Updated July 13, 2021. Accessed July 20, 2021. https://innovation.cms.gov/innovation-models/oncology-care

4. Radiation Oncology Model. CMS. Updated July 20, 2021. Accessed July 20, 2021. https://innovation.cms.gov/innovation-models/radiation-oncology-
model

5. Primary Care First Model options. CMS. Updated July 20, 2021. Accessed July 20, 2021. https://innovation.cms.gov/innovation-models/primary-care-first-model-options

6. Zion SR, Schapira L, Crum AJ. Targeting mindsets, not just tumors. Trends Cancer. 2019;5(10):573-576. doi:10.1016/j.trecan.2019.08.001

7. Medicare Program; CY 2022 Payment Policies under the Physician Fee Schedule and Other Changes to Part B Payment Policies; Medicare Shared Savings Program Requirements; Provider Enrollment Regulation Updates; Provider and Supplier Prepayment and Post-payment Medical
Review Requirements. Accessed July 28, 2021. https://public-inspection.federalregister.gov/2021-14973.pdf

COVER FEATURE

Clinicians and Payers Expect to Wait and See Before Embracing CMS’ MIPS Value Pathways


The Patient Protection and Affordable Care Act (ACA) established several health insurance reforms important to cancer care in the United States,

 including prohibiting insurers from denying coverage or setting higher premiums on the basis of preexisting health conditions, expanding Medicaid eligibility to adults with incomes up to 138% of the federal poverty level, eliminating the Medicare Part D coverage gap or “donut hole,” and requiring commercial insurers to cover the cost of routine care that a patient receives while enrolled in a clinical trial. Yet despite these reforms, many patients with cancer continue to experience significant financial burden

and distress associated with their care, referred to as the “financial toxicity” of cancer.

Financial toxicity is particularly prevalent among patients with blood cancer, who are increasingly treated with expensive, orally administered anticancer drugs. A rapid rise in the cost of these drugs has offset the savings patients should have seen from the closing of the donut hole.

 Consequently, many of the more than 1.3 million people in the United States who are either living with, or are in remission from, blood cancer

 face higher out-of-pocket costs than patients with other cancers.

 Additionally, patients with blood cancer report a myriad of other access barriers, ranging from lack of insurance and inadequate provider networks to coverage denials. With recent growth in the availability of health plans that do not comply with the ACA’s market reforms, these barriers are likely to grow.

In light of these challenges, there is an urgent need to identify insurance reforms that can meaningfully improve access to affordable, high-quality care for patients with blood cancer. To assess the current evidence base for such reforms, we conducted a literature review and gap analysis. Our aims were, first, to identify and categorize current evidence regarding the impact of health insurance status and type on access to care and outcomes among patients with blood cancer, and second, to identify areas of uncertainty and key research gaps.


We conducted a systematic search of Medline’s PubMed database on June 5, 2020, and an additional targeted author search on July 1, 2020. Search terms included relevant Medical Subject Headings as well as relevant blood cancer and insurance keywords. Search terms were identified by reviewing key terms in recent insurance and blood cancer publications and were developed in collaboration with experts and in consultation with an information scientist. The search was supplemented by reviewing the bibliographies of any identified review articles. The combined searches yielded 1101 articles. To identify the subset of relevant publications that would inform policymakers and the scientific field of the insurance research landscape related to blood cancer care and outcomes, we screened titles and abstracts for eligibility against a set of inclusion and exclusion criteria. Studies were eligible for inclusion if they involved patients with blood cancer at any stage on the cancer care continuum and had a focus on insurance. We included studies with insurance as the primary focus of the study and studies in which insurance was a variable or an outcome of the study. All study designs were eligible, including review articles and qualitative research. We excluded studies specifically focused on cancers other than blood cancer but included general cancer studies if they were known to or very likely to include patients with blood cancer. We excluded studies published before January 2000, those conducted outside of the United States (or its territories), and those not in the English language. We also excluded animal and in vitro studies, letters to the editor, and publication comments.

To provide an overview of the available scientific literature and a gap analysis to identify areas of uncertainty and research that are missing or underrepresented, we categorized included articles using the population, intervention, comparator, and outcomes framework

Given the scope and purpose of the review, categorization was based on a review of abstracts by a single research analyst and quality checked by a senior methodologist. We did not conduct a risk-of-bias assessment, and we retrieved full texts only for studies that did not include an abstract or when relevant information was not presented in the abstract. Abstracted categories included study title, author, publication year, sample size, study design, cancer focus, population group, insurance type, cancer continuum, comparator, and outcome. For each category, we established predefined coding variables and abstracted the main insurance-related outcome finding into a free-text field. The categorization process was primarily conducted on the information available in the study abstract.


Following title and abstract review, we identified 154 publications for inclusion, 70 of which had a direct focus on insurance as the subject of the article; of those, 39 focused specifically on blood cancers. Studies were predominantly large retrospective cohort studies often using Medicare claims data or the National Cancer Institute–funded Surveillance, Epidemiology, and End Results (SEER) registry data or SEER-Medicare data as the basis for analysis. Almost half of the retrospective studies focused on the association between insurance status or type and an outcome of interest. The remainder reported insurance as one of several factors found to be associated with a clinical outcome (eg, survival), quality of cancer care, or access to treatment. One prospective cohort study assessed the quality of cancer care for older patients provided by the Veterans Health Administration vs fee-for-service Medicare.

 Of 2 identified systematic reviews, one 2005 study was specific to blood cancer and found (from very limited quality-of-life [QOL] data) that individuals with chronic lymphocytic leukemia experience challenges obtaining health insurance.

 The other was a recent 2020 systematic review that investigated evidence related to health insurance coverage disruptions and cancer outcomes and found that those patients with coverage disruption were more likely to have advanced disease, be less likely to receive treatment, and have worse survival than their counterparts without coverage disruptions.

More than half of the identified studies addressed multiple types of insurance, and Medicare was the focus of 16% of studies. Medicaid was rarely studied as the sole focus of a study. Studies with a focus on adults (65 years and younger) were most common, addressed in one-third of all included studies, followed by adolescents and young adults (addressed in 21% of studies) and older adults (addressed in 19%). Children were a focus of just 9% of included studies, and a handful of sSutudies were not focused on any patient population but rather on physician opinion or practices.

 Of the 39 studies specific to blood cancer and insurance, none specifically focused on diverse racial and ethnic groups or patients in rural settings.

Studies tended to focus on patients in active treatment, addressed by 42% of all included studies. Survivorship was also commonly studied, addressed in almost a quarter of studies. Notably, just 2 studies addressed treatment in the context of clinical trial participation, one of which specifically focused on patients with blood cancer.

 A 2014 case study by Preussler and colleagues highlighted state variation in Medicaid coverage of complex oncology treatments for blood cancer and found that only a few states provided the recommended benefits (ie, benefits recommendations developed by multiple stakeholders) for hematopoietic cell transplantation clinical trial coverage.

Mortality/survival and access to care were among the outcomes most often studied, addressed in 35% and 33% of the 154 included studies, respectively. Studies addressing access to care were broad and included the impact of insurance status and type on receipt of or timeliness of treatment; health care utilization; and access to specialist care, high-cost treatments, and financial assistance such as cost-sharing subsidies. Very few studies focused on the relationship between insurance coverage and the occurrence of treatment-related adverse events (TRAEs) or cancer recurrence, and among studies specifically focused on blood cancers, very few addressed the relationship between insurance and quality of care or QOL. Similarly, very few studies investigated insurance-related disparities in health outcomes based on race/ethnicity or on socioeconomic factors.


Key Insurance-Related Findings and Gaps Specific to Blood Cancer

. Fifty-six percent of studies that focused specifically on blood cancer and insurance (22 of 39) reported survival as an outcome of interest. Of these, 21 examined the impact of insurance status or type on survival (

). Seventeen studies found disparities in overall survival (OS) based on insurance status and type,

2 reported no difference in OS based on insurance type,

 All but one study reporting survival disparities were large retrospective registry studies, and overwhelmingly, they reported better survival among patients with insurance compared with those with no insurance and better survival among patients with private commercial insurance compared with other insurance types. In contrast, the 2 studies reporting no difference in OS based on insurance type were small chart reviews.

Of the 2 studies reporting mixed survival outcomes, both were large registry database studies. One found increased OS among Medicaid-enrolled beneficiaries compared with non–Medicaid-enrolled beneficiaries (with the non-Medicaid group including both commercially insured and uninsured patients) with acute myeloid leukemia and Hodgkin lymphoma enrolled in New York State; however, there was no such difference in survival among Medicaid beneficiaries enrolled in California.

 In a 2015 study, Olszewski and Foran found that when confounding factors are considered, insurance-associated lymphoma survival disparities are partly mediated by the prevalence of known prognostic factors or by patients’ preexisting medical conditions that at the time drove eligibility for Medicaid and Medicare; these authors noted that cancer registries generally do not contain information about comorbidities or other confounders.

One study assessed the timeliness of care (defined as time from payer approval to actual HCT) and its impact on OS for patients who underwent hematopoietic cell transplantation (HCT).

Total time to HCT was longer for patients insured by public payers than for those with private insurance (median, 66 days [range, 14-277] vs 48 days [range, 1-407]; 

 < .001), but timeliness was not associated with OS.

 Thirteen of 39 studies that focused specifically on blood cancer included financial burden as an outcome of interest.

  Overall, the findings point to a significant insurance-related financial burden for patients with blood cancer. Notably, most studies addressed financial burden among Medicare beneficiaries, whereas few studies investigated the size and impact of the financial burden placed on uninsured patients and Medicaid beneficiaries with blood cancer. Of 13 studies, 8 focused on Medicare Part D. Of these, 5 reported increased financial burden on patients related specifically to high cost-sharing under Medicare Part D,

 3 of which also reported that high cost-sharing under Medicare Part D was associated with reduced or delayed initiation of specialty drugs (ie, tyrosine kinase inhibitors [TKIs]).

 The other 3 studies addressing Medicare Part D looked at low-income subsidies among recipients; one found that among Medicare beneficiaries without low-income subsidies, the introduction of Medicare Part D discounts provided during the Part D coverage gap phase decreased patients’ financial burden

the second reported a substantial financial barrier to accessing orally administered anticancer therapy for those not receiving low-income subsidies.

 The third study found that compared with Medicare Part D recipients who did not receive low-income subsidies, those patients who were heavily or moderately subsidized demonstrated greater nonadherence to TKI treatment.

This study demonstrated an association between low-income subsidies and nonadherence but did not claim that low-income subsidies cause nonadherence.

 Unrelated to Medicare Part D, a small study found that among 20 US cancer center directors and chief medical officers surveyed, 15 were concerned about the financial viability of their chimeric antigen receptor T-cell immunotherapy programs, citing Medicare reimbursement rates and manufacturer prices as the primary drivers of viability concerns.

Two studies reported financial burden for those with commercial health insurance. A 2014 study
reported on the financial burden associated with higher copayments,

and a 2001 (pre-ACA) study
reported that 61% of survey respondents paid out of pocket for some aspect of medical care that was not covered by their health insurance coverage following a diagnosis of hairy cell leukemia.

 Just one study from 2015 reported on the financial burden for Medicaid beneficiaries with blood cancer,

 and a 2011 study reported on the costs of inpatient treatment for uninsured patients with acute myeloid leukemia.

. A few studies analyzing pre-ACA data highlighted the difficulty in obtaining
health insurance (or in navigating gaps in insurance) following a blood cancer diagnosis.

 Expanding access to comprehensive health insurance coverage was a primary mission of the ACA,

 and now, post ACA, a blood cancer diagnosis is no longer the threat it once was to a patient’s ability to enroll and stay enrolled in a health plan. Although multiple studies have examined the impact of the ACA on insurance coverage and insurance-related outcomes pre- and post implementation, only one pre-post ACA study was found to have focused on a population of patients with blood cancer. In a 2019 registry study, Ramachandran and colleagues observed no
difference in the rates of newly diagnosed cutaneous T-cell lymphoma by insurance type (defined as uninsured, Medicaid insured, and non-Medicaid insured) before and after full implementation of the ACA.

 This was true when looking across all states, whether Medicaid expansion or nonexpansion states.

 Also related to access, one study found that lack of insurance was associated with advanced stage of Hodgkin lymphoma diagnosis.

 Only one study looked at insurance-related access to clinical
trial participation for patients with blood cancer. A 2014 case study investigating the variation in Medicaid policies among states in 2012 found that only a few states provided the recommended benefits (ie, recommended benefits developed by multiple stakeholders) for hematopoietic cell transplantation clinical trial coverage.

 A number of studies reported an association between race/ethnicity and blood cancer outcomes, with poorer outcomes for patients who are Hispanic, African American and non-Hispanic Black.

 However, just 2 examined whether race/ethnicity remained associated with varying outcomes after adjusting for insurance status,

 and both found that race/ethnicity was no longer significantly associated with blood cancer outcomes when regression models were adjusted for insurance status.

. Only a handful of blood cancer–specific studies addressed quality
of care

 as outcomes of interest, and these were not primary outcomes of any of the identified studies. The relationship between these outcomes and insurance status among patients with blood cancer remains largely unknown.


A modest body of scientific evidence suggests that survival among patients with blood cancer is 
affected by insurance status and type, with better OS among the insured vs the uninsured and better OS among those with commercial insurance vs public insurance. Similarly, studies of registry and claims data suggest a significant insurance-related financial burden for patients with blood cancer.

However, a number of limitations are associated with the existing literature, which ultimately hinder
the development of evidence-based policymaking in this area. Evidence of the associations among insurance status, insurance type, survival, and financial burden are based primarily on retrospective cohort studies that may fail to control for comorbidities and confounders. Additional studies, including prospective cohort studies and large well-controlled registry studies examining the impact of insurance on survival and financial burden, could confirm current findings and delve into key subgroups. Almost no current research is focused on important outcomes beyond survival and financial burden, such as the impact of insurance on clinical trial participation, quality of care, HRQOL outcomes, TRAEs, and cancer recurrence. Access to trials, in particular, has been of longstanding interest to policymakers; Congress recently passed the Clinical Treatment Act to improve trial-related coverage for Medicaid beneficiaries. Implementation of this law would be enhanced by research exploring whether uninsurance or underinsurance might continue to act as a barrier to trial participation in the future, as well as the reforms that would be needed to address such barriers in full.

Few studies have focused on diverse racial and ethnic groups, patients with low income, Medicaid beneficiaries, uninsured patients, and patients residing in rural settings. Similarly, relatively few studies have focused on adolescents and young adults, and just 14 studies (9%) focused on families with a pediatric patient. As a result, little is known about the impact of insurance on blood cancer care within these vulnerable populations. Although policymakers have expressed commitments to addressing health disparities, evidence-based policymaking in this area will be constrained by the gaps in this literature.

No peer-reviewed studies have examined blood cancer outcomes related to short-term, limited-duration health plans and other types of insurance-like products (eg, fixed indemnity plans or health care sharing ministries) that do not comply with the ACA’s market reforms and thus require plan enrollees to assume significant financial risk. With several million people already enrolled in some of these plan types,

it is critical to know the extent to which such coverage contributes to large-scale financial toxicity for patients living with costly diseases like blood cancer.


No studies have evaluated the implementation of interventions designed to improve access to or use of insurance among patients with blood cancer (eg, patient navigators focused on insurance access; insurance-related education programs). Implementation research should examine the methods and strategies that facilitate the uptake of evidence-based insurance-related programs and guidelines into practice. Such research would be timely because the Biden administration has identified increased enrollment in qualified health plans as necessary to stabilize the ACA’s insurance marketplaces, and policymakers have recently expressed a desire to curb broker practices that steer unwitting patients to inferior health insurance plans.


The current body of peer-reviewed literature provides evidence that insurance status and type affect OS and financial burden for patients with blood cancer. However, evidence is insufficient on the impact of insurance on other important outcomes, including clinical trial participation, quality of care, and HRQOL. In addition, evidence specific to key vulnerable populations is insufficient. Further research is needed to guide policymaking in these areas and to help patients effectively navigate the health insurance marketplace, gain better access to high-quality care, and achieve better health outcomes. 

Karen Crotty, Katherine Treiman, Candi Wines, and Catherine Viator are with RTI International; Marialanna Lee, Maria Sae-Hau, and Elisa Weiss are with The Leukemia &
Lymphoma Society.

 Karen Crotty, RTI International, 3040 E Cornwallis Road, Hobbs 139, P.O. Box 12194, Durham, NC 27709. E-mail: kcrotty@rti.org.

. This work was funded by The Leukemia & Lymphoma Society.


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Health Insurance, Blood Cancer Care, and Outcomes: A Literature Review 

Zanubrutinib Improves Outcomes Compared With Ibrutinib in R/R CLL/SLL, ALPINE Study Shows

Inhibition of Bruton tyrosine kinase (BTK) has transformed the treatment of chronic lymphocytic leukemia (CLL). While ibrutinib has led the way, zanubrutinib, a next-generation BTK inhibitor, has the potential to change treatment again.

Zanubrutinib improves outcomes and reduces toxicity because it minimizes  off-target inhibition of TEC- and EGFR-family kinases, which is seen with ibrutinib, explained Peter Hillmen, PhD, MBChB, professor at the University of Leeds and honorary consultant hematologist at Leeds Teaching Hospitals NHS Trust.

Hillmen presented the interim results of the phase 3 ALPINE study during the Presidential Symposium at the European Hematology Association 2021 Virtual Congress (EHA2021 Virtual).

ALPINE is a global, randomized, phase 3 study comparing zanubrutinib with ibrutinib in patients with relapsed/refractory (R/R) CLL/small lymphocytic leukemia (SLL). In the preplanned interim analysis, the data cutoff occurred at 12 months after randomization of the first 415 patients.
The patients were randomized 1:1 to receive either zanubrutinib 160 mg twice a day (n = 207) or ibrutinib 420 mg once a day (n = 208). The baseline patient and disease characteristics were well balanced between the 2 arms, according to Hillmen.

The primary end point was overall response rate (ORR), defined as partial response (PR) plus complete response. Secondary end points were atrial fibrillation, duration of response, progression-
free survival (PFS), overall survival (OS), time to treatment failure, PR with lymphocytosis or higher, patient-reported outcomes, and safety. ORR was “definitely superior” for zanubrutinib, Hillmen said. The ORR for zanubrutinib was 78.3% (95% CI, 72.0%-83.7%) vs 62.5% (95% CI, 55.5%-69.1%)
for ibrutinib. The 12-month PFS was 94.9% for zanubrutinib vs 84.0% for ibrutinib. At 18 months, 20 patients on zanubrutinib had progressive disease compared with 42 patients on ibrutinib. OS wasn’t significantly different: 97.0% for zanubrutinib vs 92.07% for ibrutinib.

The majority of patients had an adverse event (AE), but zanubrutinib had fewer AEs leading to discontinuation (7.8% vs 13.0%) and fewer deaths due to AEs (3.9% vs 5.8%). Zanubrutinib had a slightly higher rate of neutropenia (28.4% vs 21.7%), but grade ≥3 infections were lower (12.7% vs 17.9%). The interim analysis also evaluated atrial fibrillation/flutter, which was a prespecified safety end point. The rate was significantly lower with zanubrutinib (2.5%) compared with ibrutinib (10.1%).

“These data support that more selective BTK inhibition, with more complete and sustained BTK occupancy, results in improved efficacy and safety outcomes than a less-specific BTK inhibitor,” Hillmen concluded.

In the Q&A, one attendee asked about comparing the results of ALPINE with ELEVATE-RR, which was presented a week earlier at the annual meeting of the American Society of Clinical Oncology. In that phase 3 trial comparing acalabrutinib with ibrutinib in patients with relapsed/refractory CLL, acalabrutinib had a noninferior PFS and significantly fewer events of atrial fibrillation.

Comparing the two is challenging for a number of reasons, though. Hillmen noted that the second-generation BTK inhibitors are not exactly the same as one another, so it wouldn’t be surprising to see differences in terms of toxicity or efficacy. In addition, ALPINE has interim data with a median duration of 15 months compared with ELEVATE-RR’s 3 years.

“We need to see more maturity in this trial to really compare,” Hillmen said. The ALPINE abstract was submitted to the meeting as a late-breaking abstract, so the data are still being analyzed.

However, one thing was apparent from both trials: “[T]he tolerability of the second-generation BTK inhibitors…is improved,” Hillmen said.¯



Hillmen P, Eichhorst B, Brown JR, et al. First interim analysis of ALPINE study: Results of a phase 3 randomized study of zanubrutinib vs ibrutinib in patients with relapsed/refractory chronic lymphocytic leukemia/small lymphocytic lymphoma. Presented at: 2021 European Hematology Association Virtual Congress; June 9-17, 2021; Virtual. Abstract LB1900.

Pair of Studies Highlight Zanubrutinib Tolerability, Efficacy, Utility

Building on positive results presented at last year’s American Society of Hematology annual meeting, a pair of studies presented at EHA2021 Virtual, this year’s annual meeting of the European Hematology Association, added heft to the advantages of zanubrutinib over other Bruton tyrosine kinase (BTK) inhibitors for several hematologic cancers.

Zanubrutinib is a second-generation BTK inhibitor known to have fewer off-target effects among both treatment-naïve and treatment-experienced patients. It is currently approved for use in patients with mantle cell lymphoma (MCL), while the FDA has accepted a supplemental new drug application (sNDA) for Waldenstrom macroglobulinemia²(WM) with a projected Prescription
Drug User Fee Act target date of October 18, 2021. In addition, zanubrutinib’s sNDA for its use among adults with marginal zone lymphoma (MZL) received a priority review designationin May.

 which took place in China, encompassed 91 patients with a median age of 61 years (range, 35-87) who had relapsed/refractory (R/R) chronic lymphocytic leukemia (n = 82) or small lymphocytic leukemia (n = 9) (CLL/SLL). Their most common poor prognostic indicators were unmutated IGHV gene (56.0%), del(17p) or TP53 mutation (24.2%), and del(11q) (22%). A high response rate was seen among those with del(17p) and/or TP53 mutation (91%; 95% CI, 70.8%-98.9%), while all with del(11q) responded (100%; 95% CI, 83.2%-100.0%). These results add to²data previously published²from the same trial, which demonstrated that zanubrutinib had a favorable benefit-risk profile.

In the present phase 2 study, patients received zanubrutinib 160 mg twice daily until disease progression or unacceptable toxicity. By the end of the follow-up period (median, 33.9 months; range, 0.8-41.4), 34.1% of patients had discontinued treatment because of progressive disease or adverse events. However, 65.9% remained on zanubrutinib.

Overall, 69.2%, 12.1%, and 6.6% had a partial response (PR), PR with lymphocytosis, or complete response, respectively; 3.3% each had stable or progressive disease or discontinued treatment before the first assessment; and 2.2% were not evaluable. In total, 87.9% (95% CI, 79.4%-93.8%) of the entire study cohort had a response.

With additional primary efficacy end points of duration of response (DOR) and progression-free survival (PFS), the authors’ analyses revealed:

• 24-month DOR: 83.4% (95% CI, 73.2%-90.0%)
• 36-month DOR: 69.9% (95% CI, 57.0%-79.6%)
• 24-month PFS: 85.0% (95% CI, 70.5%-87.4%)
• 36-month PFS: 68.1% (95% CI, 56.6%-77.4%)

The most common nonhematologic and hematologic adverse effects (AEs) were upper respiratory tract infection in 56.0% of patients and neutropenia in 78.0%, respectively.

Results of the second study,3²the BGB-3111-215 trial, support using zanubrutinib as a treatment option following previous treatment failure. These preliminary results were seen among 44 patients who received zanubrutinib (either 160 mg twice daily or 320 mg once daily) following intolerance to the first-generation BTK inhibitors ibrutinib (n = 39) or acalabrutinib (n = 1), with 4 patients having received both. Among this cohort, 34 had CLL, 6 had WM, and 2 each had MCL and MZL. Their median age was 70.5 years (range, 49.0-91.0), and all received at least 1 zanubrutinib dose post enrollment.

Data accumulated up to the November 1, 2020, cutoff showed that among the 44 patients, 43 were still on treatment. Among those who previously were on ibrutinib or acalabrutinib, 82.8% and 77.8%, respectively, did not have a recurrence of intolerant events, of which there were 87 with ibrutinib and 9 with acalabrutinib. This breaks down to a median 2 per patient (range, 1-5).

Among the patients who did have an intolerant event recur, the events were of a lower severity in 86.7% of previous-ibrutinib patients and 50% of previous-acalabrutinib patients.

Following administration of zanubrutinib in the patients, no deaths were reported. However, 77.3% did report an AE (myalgia, 20.5%; confusion, 18.2%; dizziness, 15.9%; fatigue, 15.9%; cough, 11.4%), 13.6% reported a grade >3 AE, and 2.3% reported a serious AE. In addition, 13.6% and 4.5% required dose interruption and dose reduction, respectively. No patients required treatment stoppage.

Overall, all patients with efficacy data available maintained response (38.5%) or had a deepening response (61.5%) to the newer BTK inhibitor. “Zanubrutinib provided an additional treatment option after intolerance to other BTK inhibitors,” the authors concluded, “demonstrating tolerability and sustained or improved efficacy.”



1. BeiGene announces U.S. FDA acceptance and priority review of supplemental new drug application for Brukinsa (zanubrutinib) in marginal zone lymphoma. News release. BeiGene; May 19, 2021. Accessed July 21, 2021.https://bit.ly/2SUcy0Y
2. Xu W, Yang S, Zhou K, et al. Zanubrutinib monotherapy in patients with relapsed or refractory chronic lymphocytic leukemia: 34-month follow-up results. Presented at: European Hematology Assocation Virtual Congress; June 9-17, 2021; abstract EP639. https://bit.ly/3zot751
3. Shadman M, Sharman JP, Levy MY, et al. Preliminary results of the phase 2 study of zanubrutinib in patients with previously treatment B-cell malignancies intolerant to ibrutinib and/or acalabrutinib. Presented at: European Hematology Assocation Virtual Congress; June 9-17, 2021; abstract EP642. https://bit.ly/3wQhiTz


New Phase 2 Results From MAGNOLIA Are Positive for Zanubrutinib

August 2021

From the Editor-in-Chief: Shiny New Objects Within a Struggling System

Clinicians and Payers Expect to Wait and See Before Embracing CMS’ MIPS Value Pathways

Health Insurance, Blood Cancer Care, and Outcomes: A Literature Review

Conference Coverage: European Hematology Association 2021 Virtual Congress

August 2021: Targeted Therapy & Immuno-Oncology

Cardinal Health Experts Outline How Research, Regulatory Approaches Can Speed Drug Approval

Genomic Testing Creates Opportunities for Collaboration Between Academic Centers, Private Sector

ASCO, COA Release Updated Standards for Oncology Medical Home