Renuka Tipirneni, MD, of the University of Michigan, was named the recipient of the 2020 Seema S. Sonnad Emerging Leader in Managed Care Research Award.

Congratulations to the 2020 Recipient of the Emerging Leader in Managed Care Research Award!

The Mediterranean diet, which is known to have health benefits, may help prevent rheumatoid arthritis in current or previous smoker.

Mediterranean Diet May Prevent RA in Current or Previous Smokers

Higher levels of the omega-3 fatty acid eicosapentaenoic acid (EPA) found in the blood appear to explain why icosapent ethyl drives down the risk of a cardiovascular (CV) event.

REDUCE-IT: Serum EPA Levels Hold Key to Vascepa's Dramatic CV Benefits

Physicians may consider high-flow nasal cannula (HFNC) as a first-line oxygen therapy in select patients with acute exacerbations chronic obstructive pulmonary disease (AECOPD), according to a study 

International Journal of Chronic Obstructive Pulmonary Disease

The study found that patients with AECOPD accompanied by hypercapnic respiratory failure had a better prognosis when they were on HFNC compared with conventional oxygen therapy (COT).

“…early use of HFNC in patients with AECOPD with acute compensated hypercapnic respiratory failure could alleviate respiratory muscle fatigue and improve CO2 retention, thereby reducing treatment failure,” wrote the investigators in the report.

COT, such as nasal catheter or venturi mask, is often used as the main respiratory support method for patients with AECOPD as an alternative to noninvasive mechanical ventilation (NIV), which can be uncomfortable and hard for patients to tolerate. HFNC is a new noninvasive respiratory support technique that delivers a conditioned, warmed, and humified air-oxygen mixture.

Investigators used a tricenter, prospective, randomized, controlled clinical trial to compare the safety and efficacy of HFNC with COT in 320 patients in Beijing, China, who were hospitalized with AECOPD with hypercapnic respiratory failure.

The patients, aged 40 years and older, were assigned randomly 1:1 to receive either HFNC (n = 160) or COT (n = 160) for at least 15 hours per day for at least 5 days. The study was conducted from June 2015 to July 2019.

The primary end point was treatment failure, meaning that a patient needed mechanical ventilation (either NIV or invasive mechanical ventilation [IMV]). The attending clinician made the decision of whether patients needed to switch to mechanical ventilation based on persistent or worsening dyspnea, persistent abdominal paradox, respiratory rate of more than 25 breaths per minute, and/or a pH of less than 7.35.

During the study, treatment failure occurred significantly less for patients receiving HFNC than COT, occurring in 10% (16) of patients in the HFNC group compared with 19.4% (31) patients in the COT group (

 = .026). NIV was needed for 13 (8.1%) of the patients receiving HFNC and 26 (16.3%) of those who received COT. No patients required intubation or IMV interventions.

Additionally, the partial pressure of CO2 (PaCO2) of the HFNC group 24 hours after recruitment was lower than the COT group (54.1 ± 9.79 mmHg vs 56.9 ± 10.1 mmHg, 

= .030). However, the investigators noted that PaCO2 higher than 59 mmHg after HFNC for 24 hours was an independent risk factor for treatment failure (odds ratio [OR] 1.078, 95% CI 1.006-1.154, 

“Therefore, we suggest that in addition to optimized COPD therapy, appropriate oxygenation devices should be used on select patients to achieve the most optimal outcome,” wrote the investigators.

Secondary end points of COPD assessment test (CAT) scores and subjective discomfort on the fifth day were significantly lower for patients in the HFNC group (16.3 ± 7.2 and 2.27 ± 1.06, respectively; 

= .002) than those in the COT group (20.4 ± 5.7 and 3.88 ± 1.64, respectively; 

The lower CAT scores among patients in the HFNC group indicated “that HFNC may have the potential to improve the symptom of dyspnea in patients with AECOPD,” noted the investigators.

They also wrote that higher comfort scores for HFNC could lead to better treatment compliance for patients, which may have contributed to the lower rate of treatment failures compared with the COT group.

The most common side effects reported were condensate noise (26.3%), excessive or insufficient gas flow (23.1%), and high temperature (14.4%). The Investigators wrote that all of the side effects subsided after they adjusted the parameters or communicated with the participants.

“High-quality randomized controlled trials in large-scale cross-regional areas can further investigate the efficacy and safety of HFNC in a broader patient population with COPD exacerbation, which can also help identify the most appropriate patients and best practices,” the investigators concluded.

Li X-Y, Tang X, Wang R, et al. High-flow nasal cannula for chronic obstructive pulmonary disease with acute compensated hypercapnic respiratory failure: A randomized, controlled trial.

. 2020;2020(15):3051-3061. doi:10.2147/COPD.S283020

Articles

A recent study found that high-flow nasal cannula may be a better option for first-line oxygen therapy for patients with chronic obstructive pulmonary disease with acute compensated hypercapnic respiratory failure than conventional therapy options.

HFNC May Improve AECOPD Prognosis Better Than Conventional Therapy

To address a possible “twindemic” of coronavirus disease 2019 and influenza and the ongoing health issues in vulnerable communities, and to help rebuild trust among these communities, the health care industry must directly and consistently engage with communities of color to foster authentic relationships with those who already have long-standing connections, visibility, and trust in these communities. In addition, it has to listen and act on recommendations from this coalition, as well as look at health care in terms of preventive social determinants of health—issues that determine better or worse health outcomes for individuals.

In September, the United States surpassed 200,000 deaths from the coronavirus disease 2019 (COVID-19) pandemic, with some experts predicting that the death toll could nearly double by the end of 2020. September also marked the start of fall and the beginning of the influenza season, which, although not as deadly as COVID-19, accounts for approximately 20,000 deaths annually. This year, the fall season is accompanied by an urgent warning of an impending “twindemic” of COVID-19 and influenza by the CDC.

COVID-19 has affected our lives in ways we could never have imagined and has made many of us more attuned to our overall health and the need for preventive measures. A recent poll

 conducted by EmblemHealth found that nearly half of New Yorkers surveyed are more likely to get the influenza vaccination this year than in years past, and health systems across the country are reporting unprecedented demand for influenza vaccinations. But, as the past few months have revealed, access to health care in our country is deeply unequal, especially for communities of color. Nowhere has this been more apparent than in New York, the original epicenter of the COVID-19 pandemic in the United States and a microcosm of the devastating impact that racial disparities have on the health of our communities.

At the height of the pandemic in April, Black New Yorkers were dying at a higher rate than any other racial and ethnic group, and at twice the rate of White New Yorkers.

 As the CDC warns of a surge this fall and winter, these rates collide with the sobering statistics around influenza vaccination adoption. Among the 1005 New Yorkers who responded to EmblemHealth’s survey, Black women were significantly less likely to seek access to the influenza vaccination this year than any other group. Only 35% of Black women stated that they have received the influenza vaccination consistently over the past 3 years, compared with 56% of New York City’s general population. Concerns about effectiveness and safety were listed as top reasons to not get the influenza vaccination, which foreshadows the challenges that we may also face when the COVID-19 vaccine becomes available.

As a physician and a Black woman, I view these findings as alarming but, unfortunately, not unexpected. Over several decades, the health care industry has sown mistrust among communities of color, for reasons ranging from the Tuskegee syphilis experiment in the 1930s to the underrepresentation of Black patients in research and vaccine trials that persists to this day.

 In many cases, the former has shaped the latter, with the historical legacy of exploitation fueling the ongoing distrust of research and health care systems in the United States. In the case of Black women and the twindemic, this has the potential to be a lethal combination.

Although COVID-19 has exhibited deadlier consequences among men, women often hold jobs that put them at a higher risk of infection, such as domestic workers, nurses, or home health aides. A 

 analysis of Census data earlier this year found that 1 in 3 jobs held by women have been categorized as “essential,”

 and data from the Center for Economic and Policy Research indicated that women of color were more likely to have essential jobs.

 Although many female essential workers struggle with taking time off for routine care, the primary deterrents to getting the influenza vaccination among Black women are concerns about effectiveness, safety, and adverse effects. All of these fears are heightened by the ongoing political interference in public health practices and messaging. Nevertheless, the remedy to the fear and uncertainties among underrepresented and disenfranchised communities of color remains within the health care industry’s power and capacity to change.

The health of our nation is at a critical crossroads: one where Black women stand to lose the most as a consequence of historical and systemic failures and their overrepresentation on the front lines of the pandemic. But it’s not too late to enact change that will save the lives of thousands of Black women now and in the future. We can do this by engaging those who are influential in the Black community, from church leaders to hairdressers and barbers; by addressing the shortage of Black physicians,

 whose voices and experiences represent the communities they serve; and by recruiting more Black men and women to participate in research and vaccine trials—not only for the COVID-19 vaccine, but for conditions such as cardiovascular disease and cancer, of which Black individuals have the highest death rate

 and the shortest survival compared with any other racial and ethnic group in the United States.

The consequence of populations of color not being represented in research, testing, and vaccinations is that, ultimately, we will not have equitable access to cures, and without community empowerment, we are doomed to repeat history’s mistakes. Black women and our families deserve better, and our lives depend on it.


 The author reports no relationship or financial interest with any entity that would pose a conflict of interest with the subject matter of this article.

 Acquisition of data; analysis and interpretation of data; drafting of the manuscript; critical revision of the manuscript for important intellectual content; statistical analysis; provision of patients or study materials; administrative, technical, or logistic support; and supervision.

 Diane M. Ashton, MD, MPH, EmblemHealth, 55 Water St, New York, NY 10041. Email: dashton@emblemhealth.com.

1. EmblemHealth study finds New Yorkers overall more likely to seek flu vaccine this year amid COVID-19. News release. EmblemHealth; October 1, 2020. Accessed October 21, 2020. https://www.emblemhealth.com/news/press-releases/EmblemHealth-Study-Finds-NewYorkers-Overall-More-Likely-to-Seek-Flu-Vaccine

2. Black people in NYC twice as likely to die from COVID as white people: data. ABC News. April 17, 2020. Accessed October 21, 2020. https://abcnews.go.com/US/black-people-nyc-die-covid-white-people-data/story?id=70208362

3. Frederick WAI, Montgomery Rice V, Carlisle DM, Hildreth JEK. We need to recruit more Black Americans in vaccine trials. 

. September 11, 2020. Accessed October 21, 2020. https://www.nytimes.com/2020/09/11/opinion/vaccine-testing-black-americans.html

4. Robertson C, Gebeloff R. How millions of women became the most essential workers in America. 

. April 18, 2020. Accessed October 21, 2020. https://www.nytimes.com/2020/04/18/us/coronavirus-women-essential-workers.html

5. Brown H, Rho HJ, Fremstad S. Mothers in frontline industries deserve better. Center for Economic and Policy Research. May 8, 2020. Accessed October 21, 2020. https://cepr.net/mothers-in-frontline-industries-deserve-better/

6. Sobowale K. We need more Black physicians. 

. July 17, 2020. Accessed October 21, 2020. https://www.scientificamerican.com/article/we-need-more-black-physicians/

Cancer Facts & Figures for African Americans 2019-2021

. American Cancer Society. 2019. Accessed October 21, 2020. https://www.cancer.org/content/dam/cancer-org/research/cancer-facts-and-statistics/cancer-facts-and-figures-for-african-americans/cancer-facts-and-figures-for-african-americans-2019-2021.pdf

This year, the fall season is accompanied by an urgent warning from the CDC of an impending “twindemic” of coronavirus disease 2019 and influenza. Despite the warnings, Black women are not lining up for vaccinations.

Why Even the Threat of a Twindemic Isn’t Swaying the Most Vulnerable: Black Women

Polling employees on their health and retirement benefits annually over the past 2 decades, the 

 by Willis Towers Watson (WTW) was highlighted as a special edition looking at the impact of the coronavirus disease 2019 (COVID-19) pandemic and its associated economic hardships on US employees.

For this year’s poll, WTW surveyed 4898 US employees of large private sector organizations in October 2020 on a myriad of aspects, notably, the exponential growth of virtual care and telemedicine, as well as deferral in medical care precipitated by the pandemic.

In first delving into the rise of telehealth, the survey indicates that nearly half of respondents (47%) have used virtual care this year, marking a substantial increase from just 17% of employees in last year’s survey. When asked on the comparable efficacy between virtual and in-person consultation, 8 in 10 employees (79%) regarded both approaches as equally effective, with 1 in 4 rating virtual care as better.

Moreover, the benefits of virtual care were seen prominently for low-income employees who were more than 40% more likely to say they got the care they needed when using virtual care. Employees with mental health issues were also significantly more likely to say they are receiving the care they need through virtual care.

“Employers were quick to expand and educate employees on how to access virtual care, and employees–especially those who were hesitant to access traditional medical care–took advantage of it,” Julie Stone, managing director of Health and Benefits at WTW, said in a 

. “While most employees used virtual care for regular screenings and checkups, a significant number were able to utilize it for diagnosis and treatment of a new illness, chronic conditions, and importantly, 

In another key takeaway from the survey, 44% of respondents were reported to have deferred medical care since the start of the pandemic, with 42% of this group citing money concerns and 61% noting fears of COVID-19 exposure. Among those who deferred care, nearly 3 in 10 employees (29%) said their health suffered as a result of cancelling an appointment or treatment, while 40% expect their health will suffer.

Looking at a post-pandemic world, 29% of employees who deferred care said they will increase their health care use when the pandemic ends, a sentiment shared starkly among those with chronic conditions as 53% of this subgroup who deferred care reporting plans to increase health care use.

In addressing this deferral in care, Jeff Levin-Scherz, MD, co-leader of Health Management Practice at WTW, said in an email exchange with 

 that data points to a substantial decrease in preventive care during the pandemic. This could have significant implications for employers as severity of undetected conditions, such as cancer, may intensify over time and subject both the employer and employee to higher health care costs.

“Employers can use their communications channels to encourage their members to keep children up to date on pediatric vaccines, which can prevent epidemics and lower total costs–they can also encourage cancer screening at recommended intervals–and in the case of colon cancer screening they can offer access to home testing which is a reasonable alternative to colonoscopy for those not at high risk-based on family or personal history,” said Levin-Scherz. 

“Employers have also increased access to virtual care—which has improved access to much-needed mental health services, and is a promising way to improve chronic disease care, too.”

A survey by Willis Towers Watson finds significantly increased use and noted satisfaction in virtual care among the US workforce amid the coronavirus disease 2019 pandemic.

Survey Finds Increased Utilization of Virtual Care, Deferral in Preventive Care Among US Employees

 indicate encouraging steps forward in the global fight against coronavirus disease 2019 (COVID-19). But all 3 vaccines are still a long way from becoming readily available to the wider public, prompting the question, who should be prioritized once doses become available?

To provide guidance on this front, the National Institutes of Health (NIH) and CDC requested The National Academies of Science, Engineering, and Medicine (NASEM) to construct a 

 assisting US policy makers and global health communities to plan for an equitable allocation of a COVID-19 vaccine.

On this episode of Managed Care Cast, we speak with Jewel Mullen, MD, MPH, the associate dean for health equity and associate professor of population health and internal medicine at the University of Texas at Austin, 

. Mullen is the former principal deputy assistant secretary for health in HHS and a member of the National Academies committee which developed the framework for vaccine allocation.

Mullen discusses criteria used to prioritize vaccine recipients, barriers to equitable distribution, and the role of misinformation in the push for an effective COVID-19 vaccine.

Listen above or through one of these podcast services:

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Recently released vaccine data indicate encouraging steps forward in the global fight against coronavirus disease 2019 (COVID-19). When vaccine doses first become available, who should be prioritized? 

Dr Jewel Mullen Discusses NASEM's Framework for an Equitable Distribution of a COVID-19 Vaccine

 since 2019 and has a BA in philosophy and journalism & professional writing from The College of New Jersey. 

 outlines the benefits of structuring negotiations and standardizing fee-for-service 

 independent of any specific reform proposals to control health care spending in 3 high-income countries.

“Although the US has the highest health care prices in the world, the specific mechanisms commonly used by other countries to set and update prices are often overlooked, with a tendency to favor strategies such as reducing the use of fee-for-service reimbursement,” authors wrote.

Studies have shown that prices in the United States are higher than in other countries not because the volume of service is greater, but because costs are higher due to private insurers’ insufficient leverage in the market and dramatic price variations in the private market.

In most countries with universal health care, physicians are paid on a fee-for-service basis, researchers explained, whereas in the United States, fee-for-service private practice and third-party payment are thought to weigh down the health care system with financial incentives. US policy makers instead support more focus on market competition, managed care, price transparency, and performance measurement.

To better understand how France, Germany, and Japan appear to achieve economic sustainability in a fee-for-service system, researchers focused on how the governments balance the needs of physicians, patients, and insurers. In the 3 countries, legal residents are covered under universal health insurance by multiple insurers operating within a national statutory pricing framework for provider fees. Competition occurs among health care providers, not insurers, and plan enrollment is determined by an individual’s occupation.

Investigators reviewed and translated fee schedules, payment policy descriptions, reports and policy documents. They also sought assistance from health policy experts to identify interviewees. A total of 37 individuals (14 in France, 11 in Germany, and 12 in Japan) were interviewed between 2016 and 2018.

“In the course of our interviews…we sought to understand the process for creating physician fee schedules and updates, learn about recent policy changes in physician payment, and identify the remaining challenges in the use of fee-for-service payment to physicians,” authors wrote.

Although Japan, Germany, and France all negotiate fees in the context of expenditure constraints, the countries have different institutional processes to address health care prices and volumes. Researchers found:

France has negotiated prices aggressively but has few controls over the volume of care.

Germany controls service volume indirectly by imposing budget caps on sickness funds and physician associations and putting them in charge of enforcing volume controls.

Japan institutes a complex set of conditions that govern how and where health care services can be provided; the country aims to constrain volume by limiting the volume of services billable for each item.

Japan limits the number and types of hospitals, clinics, and physicians allowed to provide particular services.

Although France and Germany hold physician fees at lower levels than in the United States, both countries pay specialists more than primary care physicians.

In France and Germany, fee schedules reflect a bias for more technical or procedural services over services like office visits in primary care.

Japan pays private office–based generalist physicians, represented by the Japan Medical Association, more than academic hospital–based specialists.

Overall, the 3 health systems focus on controlling prices in the context of fee-for-service medical practice and national expenditure constraints that do not result in withholding health care for the population, authors wrote.

In the United States, the myriad of payment arrangements inhibits unified approaches and creates a growing pressure to change and standardize fees. In the absence of universal coverage, authors argued that the United States should regulate how much discretion providers of health care services have in setting their own prices.

“The ways and means by which France, Germany, and Japan are ‘getting the price right’ should not be ignored by US policy makers concerned with universal health insurance or with the incremental extension of affordable health insurance coverage,” the researchers concluded.

Gusmano MK, Laugesen M, Rodwin VG,  Brown LD. Getting the price right: how some countries control spending in a fee-for-service sysyem. 

 2020;39(11):1867-1874. doi:10.1377/hlthaff.2019.01804

An analysis published in Health Affairs outlines the benefits of structuring negotiations and standardizing fee-for-service payments independent of any specific reform proposals to control health care spending in 3 high-income countries.

How Japan, Germany, and France Control Spending in a Fee-for-Service System 

More than 3 years after FDA approved the first options in chimeric antigen receptor (CAR) T-cell therapy, Bristol Myers Squibb (BMS) awaits word on whether its investigational treatment, lisocabtagene maraleucel (liso-cel) will be approved. 

, BMS announced that FDA would not meet its target approval date due to the agency’s inability to complete inspections at a third-party manufacturing site, because of travel restrictions related to the coronavirus disease 2019 pandemic. A new target date has not been announced.

If approved, liso-cel will give patients another option for the treatment of relapsed or refractory (R/R) large B-cell lymphoma, if their disease has progressed after at least two prior therapies. Like its predecessors, liso-cel targets CD19, a surface glycoprotein seen in B-cell development that remains present when the cells become malignant. According to information from Bristol Myers Squibb, the liso-cel CAR mechanism features the following:

an anti-CD19 single-chain variable fragment targeting domain for antigen specificity

a 4-1BB costimulatory domain intended to increase T-cell proliferation and persistence

In addition, liso-cel’s distinct manufacturing process creates a defined composition of CD8+ and CD4+ T-cells, which may reduce product variability; however, the 

, “the clinical significance of defined composition is unknown.”

For insights on what the arrival of liso-cel could mean in the treatment landscape

, director of the Chronic Lymphocytic Leukemia Program at Toni Stephenson Lymphoma Center and associate clinical professor, Department of Hematology & Hematopoietic Cell Transplantation at 

(axi-cel), sold as Yescarta, and the TRANSCEND NHL trial for liso-cel.She has addressed major scientific meetings on the challenge of managing the toxicities associated with CAR T-cell therapy—and discussed how liso-cel represents 

This interview, conducted before the BMS announcement, has been edited for clarity and length.

We're anticipating an FDA decision on liso-cel before the end of the year. Can you discuss the need of the patients who would take this new CAR T-cell therapy?

So, for CAR T-cell therapy targeting CD19-positive B-cell lymphomas—specifically aggressive B-cell lymphomas—we already have a couple of FDA-approved options. The question is: what is liso-cel? How is it different? Why would people pick this over other things? In the trials that we've conducted, we found that liso-cel seems to have lesser toxicity in terms of the specific CAR T-cell side effects of cytokine release syndrome or hyper-inflammation, as well as neurotoxicity. We've just seen fewer severe adverse events so much so that at some [cancer] centers across the country, we’ve been able to give liso-cel CAR T-cells to patients in the clinic or outpatient setting rather than having to admit them to the hospital , depending on the patient's situation.

Those are the strengths of liso-cel—less toxicity and thus, a better chance of giving it in the outpatient setting with hospital admission available to anyone who develops a fever or other side effects. This means fewer days of inpatient hospitalization for these patients, so it may be less costly overall. I don’t think the efficacy is necessarily different—meaning that it seems to work as well as the other FDA-approved products already commercially available. But for the reasons that I've listed, I think it might be a very good option for older patients, maybe patients who are bit more frail, or younger patients who just don't want to be admitted to the hospital—they just want to try to do it in the outpatient setting.

You touched on this already, but can you discuss how Iiso-cel differs from earlier CAR T-cell therapies—both in the way it's manufactured and how it works, and what that reduced variability means for patients?

Liso-celis manufactured in a way that it gives very precise, equal numbers of CAR cells that are labeled CD4 and CD8, in a 1:1 ratio. All of us have T cells to fight infections with, and these T cells are what we take from patients. Then, we modify them in the lab by genetic engineering in order to produce CAR T-cells so that now instead of looking for infections, these CAR T cells are going to look for B-cell lymphoma cells and fight lymphoma.

The other products are given back to patients as a bag of CAR T cells mixed with potentially varying ratios of different types of T cells—CD4+, CD8+, etc. With liso-cel the manufacturing process actually separates out the CD4+ and CD8+ types of T cells first, and then manufactures CAR-T cells out of them separately. So, when we give the cells back to patients, we give it in a 1:1 ratio of CD4+ and CD8+ cells. We know exactly how many CD4+ and how many CD8+ T-cells these patients receive. And the thought is, the researchers and the drug manufacturer feel that this helps to have an expectation of what expansion you will have of these cells in the body. 

Therefore, we potentially have an idea of what type of side effects or how severe the side effects might be. It may limit some of those side effects, or at least make them a little bit more predictable or controlled.

That’s a great way to shift to your own work on length of stay due to CRS. What do we know about the key variables in determining whether a patient will experience a side effect that requires an extended stay in the hospital, and can more be done to avoid lengthy hospital stays?

That's a very important question. Because lengthy hospital stays, especially in the [intensive care unit], really adds to the bill and the financial burden of these treatments. We know that people who have a big burden of disease going into CAR T-cell therapy, meaning they have a lot of lymphoma in their bodies, they tend to be at higher risk for more side effects like cytokine release syndrome and neurotoxicity. Probably because there's so much inflammation that’s generated while these CAR T-cells are trying to fight the lymphoma. What we know is that people who come to us for CAR T-cells with lesser disease might have fewer side effects potentially and a better overall outcome.

So, we always try to advise our referring physicians, and educate patients, at conferences, to try to send these patients to us before they are at the end of the line—before they’ve tried and failed everything, and now there’s just rampant disease. … [At that point,] you're dealing with a situation where the patient is going to have more side effects and will not be able to tolerate the CAR T cells as well. Instead, if they fail two lines of therapy and the disease is still small in volume, but it's starting to progress, we can treat them more effectively with CAR T cells and with fewer side effects potentially.

That brings up the next topic—there have been discussions that CAR T-cell therapy should be given earlier during treatment. As you said, if it’s not given as the last resort, patients might respond better. Where do you see those patterns heading in the future? And would that be truer for some patients than others?

 With aggressive diffuse large B-cell lymphoma, there's about a 60% to 70% chance of curing that in the frontline setting. With the line of chemo-immunotherapy, you can cure 60% to 70% of patients so that it never comes back. But the rest of them—when it just relentlessly keeps coming back and it's hard to cure—once those patients relapse they tend to keep relapsing. So, our mainstay in the relapse setting is to give them salvage chemo-immunotherapy, collect stem cells, and take them to autologous stem cell transplantation if they've achieved a remission with the salvage chemotherapy. If they haven't achieved remission with that salvage chemotherapy, then they should go on to CAR T cells directly instead of waiting and trying more and more chemotherapies. After failing second line therapy, the FDA approval allows us to try CAR T cells. There are studies that are now ongoing that are comparing CAR T cells to autologous stem cell transplantation after failing first line therapy. So, once patients relapse the first time, these studies are comparing giving them salvage chemotherapy and transplant, versus taking them straight to CAR T cells. Once we have that data, we'll know better whether we can do CAR T cells even earlier in the lines of therapy.

We’ve been hearing for some time more about allogeneic or “off-the-shelf” therapies. What progress has been made on in that technology?

I'm not too involved with these trials myself, but I know we have trials at City of Hope that are ongoing with off-the-shelf therapy. What I can tell you is that it's very attractive in that you don't have to collect T cells from patients, keeping their lymphoma under control while these T cells then go to the lab and CAR T cells are manufactured in 2-4 weeks depending on which product it is, and then they come back and get infused. With off-the-shelf products, you can just grab it and go as soon as you know the patient needs it.

The initial concerns were because the cells are not from the patient themselves—the cells are from donors. Across the board there might be concerns of rejection and what's called graft-versus-host disease and things like that. So far, I don't think in the trial they've come up with such side effects to any significant extent. What I don't know is whether they've come up with a good result yet. Is it looking like the benefits of taking off-the-shelf CAR T cells are as good as autologous CAR T cells, meaning patients’ own CAR T cells? I think that remains to be seen. If they are, then it's much easier to use off-the-shelf CAR T cells. Maybe at the American Society of Hematology annual meeting in December we will see more data.

 How is COVID-19 affecting the clinical trial process for CAR T cell therapy?

 When the pandemic kind of started surging early in the year, and when we went into lockdown mode from March onward, we and other centers across the country took a lot of steps to slow down our clinical trial enrollment. Our staff started staggering who would come into work which day of the week and who could work from home. For those in the clinical trials office, there was a lot of need for safety and logistical reasons for us to slow down enrollment onto clinical trials. And there were other questions, such as, who would take care of patients at home once we discharged them after they received CAR T cells? What if their caregivers were exposed and got sick? Logistically, it was difficult to safely do many trials, especially CAR T cell trials and transplants earlier in the year.

Since the end of summer, we ramped up again, and we're now doing as many transplants and CAR T cells as we were probably doing last year. So, we're pretty much all the way up again, but I don't know how this winter will go because COVID is surging again.

As far as just CAR T cells themselves, we had to also think about travel for the cells because Juno Therapeutics is in Seattle, and Kite Pharma is here in Los Angeles, but Novartis is elsewhere. Just the movement of these cells was a concern because of travel restrictions during COVID-19. But as far as I know, the companies did not lose that commitment—they told us, we’ll get the cells to you, we will find a way to do it. I don't think any patients went without cells who should have received cells.

 What advice do you have for community oncologists interested in CAR T cell therapy for their patients?

There’s good news for community physicians. We may soon have a therapeutic option of liso-cel CAR T cell therapy which seems to have lesser side effects. So, this might make things cheaper due to less need for hospitalization potentially without compromising the chance of cure. We want these patients to try CAR T cell therapy sooner rather than later in their relapses. You can always try multiple cycles of chemotherapy at some other time if you relapse again, but if you can be cured with CAR T cells such that you never need treatment again, why not try that first? For the patients who respond well to CAR T cells, the treatment works extremely well. And that's the Holy Grail – to find the cure for all patients.

Maybe only half the patients will currently have a very good and durable response—but those patients may never relapse again. So why not try it sooner rather than later? And of course, we're always looking for trial patients, because now we need to improve these results even further. So, community oncologists should also refer for trials, because I think that it’s very important to have trials with different combinations—CAR T cells plus another immunotherapy agent—to see if we can improve upon the response rates even more.

City of Hope's Dr. Tanya Siddiqi offers an update on a new chimeric antigen receptor (CAR) T-cell therapy awaiting approval from the FDA.

Tanya Siddiqi, MD, Discusses the Promise of Reduced Toxicity With Liso-Cel 

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Heart Failure With Preserved Ejection Fraction: Current Status and Future Opportunities

Disparities in cancer care have long existed, and a 

 between the Association of Community Cancer Centers (ACCC) and the American Society of Clinical Oncology (ASCO) is bringing them to the forefront. The collaboration aims to reduce racial and ethnic disparities in clinical trial participation. Randall Oyer, MD, medical director of the oncology program at Penn Medicine Lancaster General Health and 2020-2021 president of the ACCC, discusses how the collaboration came to fruition.  

What went into the decision to collaborate with ASCO on the initiative to increase minority participation in clinical trials?

Both ASCO and ACCC have a very strong mission to apply results across all communities and have a very strong social mission. Truthfully, the CEO of ASCO, Dr Cliff Hudis, noticed the similarity between this year's presidential theme in ASCO where [2020-2021 ASCO president] Dr Lori Pierce had chosen social determinants of health, and the presidency for ACCC, which was moving clinical trials out into the community. Clearly, there was overlap, and focusing on Blacks and other ethnic minorities who have been traditionally underrepresented in cancer treatment trials seemed to be something that we could do better together.

The window for idea submission closed in late August. How was the response rate?

About 30 thoughtful responses came in from ASCO and ACCC members, really highlighting how important this issue is to investigators across the country and how people have already started to work on the problem. So we were really pleased with the response. There were some top notch ideas—very difficult to sort through.

Randall Oyer, MD, president of the Association of Community Cancer Centers, discusses the ACCC and American Society of Clinical Oncology's initiative to make clinical trials more inclusive.

Dr Randall Oyer on ACCC and ASCO's Work to Reduce Clinical Trial Disparities

Due to sharp increases in coronavirus disease 2019 (COVID-19) cases, the CDC advised overwhelmed local health officials to triage contact tracing efforts, Politico 

 from the CDC states that health departments ought to prioritize which cases to investigate and which contacts to trace. Specifically, tracers should contact those who tested positive within the last 6 days, members of their immediate household, the elderly and patients with medical conditions, and individuals living or working in congregate settings. The agency also recommended against contacting infected people more than 2 weeks out from their positive test as it is likely too late to prevent them from spreading the virus.

Rural Patients With COVID-19 Sent to Strained Urban Hospitals

The sickest patients with COVID-19 residing in rural areas of America are being sent to cities and putting a strain on hospitals, according to 

. For example, although Kansas City has a mask mandate in place, many smaller communities around the city nearby do not. Rural counties in Kansas and Missouri have seen some of the highest COVID-19 rates in the country in the past few months. Roughly 3 in 4 counties in these states do not have a single intensive care unit bed, meaning critically ill patients get relocated to city hospitals. In one hospital in Kansas City, two-thirds of patients coming from rural areas needed intensive care and stayed in the hospital for an average of 2 weeks.

Texas, Louisiana Can Cut Medicaid Funding to Planned Parenthood

A federal appeals court ruled Texas and Louisiana can cut Medicaid funding to Planned Parenthood clinics, the Associated Press 

. Supporters of the ruling, handed down by the 5th US Circuit Court of Appeals in New Orleans, are opponents of federal funding going toward legal abortion, while opponents say the ruling will affect a variety of non-abortion health services for low-income women. The ruling reversed a decision blocking Texas from enforcing its ban on Medicaid funding of Planned Parenthood. The new ruling is expected to go to the Supreme Court. Advocates for women’s health argue the move will reduce access to women seeking cancer screenings, birth control, and other health services even in states where clinics do not perform abortions.

CDC pushes for prioritized contact tracing; urban hospitals struggle to keep up with influx of rural patients; Texas and Louisiana can cut Medicaid funding to Planned Parenthood. 

What We’re Reading: CDC Urges Streamlined Contact Tracing; Urban Hospitals Strained; Planned Parenthood Medicaid Funding Cut

Investigators have identified a gene signature that appears to predict whether 

 is likely to spread and whether it will be susceptible to a common therapy for advanced disease.

, could prove to be a major advancement in the care of prostate cancer and help clear up a significant area of uncertainty in patient management.

In the United States, about 33,000 men die from prostate cancer each year. Overall, the cancer has a high survival rate; 99% percent of patients are alive 5 years after diagnosis. In most cases, the disease can be managed either with active surveillance or local therapy. However, in a minority of cases, the cancer spreads, most often to the bones. Once it spreads, the disease is considered incurable with a 5-year survival rate of just 30%.

Lead author Juan M. Arriaga, PhD, of Columbia University’s Vagelos College of Physicians and Surgeons, said existing tests do not allow physicians a reliable prediction of whether a patient’s cancer will spread.

“We miss a lot of aggressive cancers that should have been treated earlier,” he said, in a press release, “and we overtreat some slow-growing cancers that probably would not have spread.”

Arriaga and colleagues decided to investigate whether there might be a better way to assess the likelihood of metastasis. The team used a murine model of prostate cancer, on which they performed transcriptomic and whole-exome analyses. That investigation led them to the discovery that bone metastases have a distinct molecular profile from primary tumors.

From there, the authors identified 16 genes that appear to be linked with prostate cancer metastasis. They called the genetic signature META-16.

Next, the investigators set out to see whether the presence of the genetic signature was predictive of outcomes in humans. They used biopsies from several hundred patients with localized prostate cancer and tested them for the presence of META-16. The investigators did not know patient outcomes at the time of the genetic analysis.

They found that the signature was highly effective at predicting both time to metastasis and whether a cancer was likely to respond to anti-androgen therapy, which is commonly used to treat advanced disease.

While they are still refining the test, the investigators said it could be a valuable tool to decide which patients are suitable for active surveillance and which are not.

“If we could know in advance which patients will develop metastases, we could start treatments earlier and treat the cancer more aggressively,” said Cory Abate-Shen, PhD, the study’s senior author. “Conversely, patients whose disease is likely to remain confined to the prostate could be spared from unnecessary therapy.”

Arriaga added that knowledge of META-16 could also lead to new therapeutic approaches.

“The genes in our signature are not only correlated with metastasis,” he said, “they appear to be driving metastasis. That means that if we can suppress the activity of those genes, we might be able to prevent the cancer from spreading or at least improve outcomes.”

The investigators said they hope to evaluate their test, once finished, in a prospective clinical trial.

 A MYC and RAS co-activation signature in localized prostate cancer drives bone metastasis and castration resistance. 

2020.1(11) 1082–1096. doi: 10.1038/s43018-020-00125-0

The discovery of a genetic signature that correlates with metastasis in prostate cancer could make it much easier for physicians and patients to choose treatment strategies.

Genetic Signature Could Predict Prostate Cancer Metastasis

Patients with epithelial ovarian cancer (EOC) who are treated with chemotherapy followed by prolonged poly-ADP-ribose polymerase inhibitors (PARP) may face a the possibility of a heightened risk of severe hematological toxicity, according to a new report.

The report, based on the experience of a single European cancer center, suggests a higher risk than was found in other, larger studies. The new data were 

and the authors noted that the cohort size is too small from which to draw any inferences 

Most patients diagnosed with EOC will undergo debulking surgery followed by platinum-based chemotherapy, explained corresponding author Elisabetta Todisco, MD, PhD, of the European Institute of Oncology, in Milan. Though such treatment is considered the “gold standard” treatment, Todisco and colleagues noted that most patients will experience a relapse. One of the most promising treatments in such cases are PARP inhibitors, which are targeted therapies that kill cancer cells by blocking enzymes that let the cells repair DNA.

The therapy works because some cancer cells have a defect limiting their ability to repair DNA double-strand breaks via the homologous recombination repair pathway, the investigators wrote.

“These cancer cells have increased dependence on PARP to repair their DNA and to divide,” they said. “For these defective cells PARPi may be lethal by triggering ‘synthetic lethality.’”

The disruption of defective cells’ repair processes might also impact non-defective cells, they added.

The new report suggests that patients treated with prolonged poly-ADP-ribose polymerase inhibitors after chemotherapy may need close hematological monitoring.


