As we live through these strange, tragic, extraordinary times, the phrase, “Trust the science” has become a mantra. The ubiquity of this phrase, with its intertwined messages of imploration and admonition, reflect the evolution of the power of social media and messaging driven by an infinitely expanding cyberspace universe. For all the silly ways in which this message has been communicated in a time when 30-second TikTok videos represent the level of discourse, there is value in acknowledging the power of science to unlock the unknown—and there is transformative value in that knowledge. Over the course of my career, progress in understanding the genetic, genomic, and epigenetic underpinnings of cancer, as well as our growing understanding of the role of the immune system in eradicating cancer cells, has unleashed a wealth of innovative and effective anti-cancer treatments. The last 2 American Cancer Society (ACS) Cancer Statistics reports demonstrated the greatest decrements in cancer mortality ever reported. In reality, the aforementioned advances in science are leading to improved survival outcomes for patients with cancer.

Not all Americans, however, realize these benefits. While it is reasonable to "Trust the science,” we need to do much more. This includes the creation of better systems of ensuring that this care is equitably available to all who need it, when they need it. Moreover, we need to ensure that the barriers of geography, distance, poverty, scientific literacy, and other social determinants of health impede equitable access to this level of care innovation. At this year’s Patient Centered Oncology Care®(PCOC) conference, presented by 

®, we heard about both advances in the science of care and exciting new models for ensuring that the life-saving benefits of cancer care advances are better realized by more patients and families. Throughout the two-day conference we heard from speakers and panelists who, while noting the growing impact of precision medicine, also described the ways in which underserved populations remained underserved. These gaps in care include access to clinical trials, trial design that fails to incorporate the needs of a diverse population, biospecimen banking practices that failed to include sufficient human diversity for the creating of new genomic analytics, the challenges of improving health literacy, and limited patient access to the requisite care expertise. Beyond the science, we need better care models that more accessible and sustainable for the underserved; we also need more effective reimbursement models that incentivize more patient access and align with greater investment into holistic and humanized care delivery. Moreover, if we are to achieve better patient outcomes and ensure more equitable patient access, our system will need to grow beyond its current ”bricks and mortar” mindset. During the PCOC meeting our discussants embraced that creative challenge and described the ways in which wearable devices, the Internet of Things, and more effective use of artificial intelligence tools to create more powerful means of engaging patients and their communities in the support of life-saving cancer care.

This year’s PCOC meeting marked a shift in our thinking. Beyond reviewing the extraordinary assets of cancer science and technology, which we have discussed for the past decade, this year began a reconsideration of the types of systems that we will need to build to find the way up beyond the limitations of our current care delivery models. As the ACS data show, the life dividend of getting better care to the millions of patients who fail to benefit fully from our current cancer care revolution is enormous. The shift toward an equitable realization of the culminated fruits of our scientific endeavors is where we venture forth toward the challenge of making the science a reality for those who need it most.

Articles

FROM THE EDITORS

From the Editor-in-Chief: The Way Up

For generations, people in New Jersey who received a diagnosis of cancer spoke of “going into the city” for treatment. 

In the northern counties, that meant New York City; further south, it meant a trip into Philadelphia. But over the past decade, the state with the fifth-highest rate of cancer incidence has invested in keeping patients closer to home, supported by evidence that travel not only exacts a toll on patients and affects outcomes, but it may also lead to longer hospital stays.

Now, Rutgers Cancer Institute of New Jersey (CINJ), the state’s only National Cancer Institute–designated Comprehensive Center, is raising the stakes.

 On June 24, New Jersey Governor Phil Murphy and a “who’s who” of the state’s health care community seized the opportunity between the state surpassing a COVID-19 vaccination goal and dealing with the Delta variant to break ground on a $750 million, 12-story building, to be known as the Jack and Sheryl Morris Cancer Center.

 This new facility was borne of a partnership between Rutgers CINJ and RWJBarnabas Health, which operates 11 acute-care hospitals across a region that is home to 5 million people.

This freestanding, dedicated cancer pavilion will offer medical, surgical, radiation, and immuno-oncology services in 1 location, giving clinicians, navigators, research staff , and support teams easy access to each another and, more importantly, to patients. The center is the mission of Steven K. Libutti, MD, FACS, who was named director of Rutgers CINJ in January 2017. Libutti also serves as vice chancellor for cancer programs at Rutgers Biomedical and Health Sciences and senior vice president for oncology services at RWJBarnabas Health.

With an aging population that is becoming increasingly diverse, Rutgers CINJ is well-positioned to serve more of the estimated 56,000 people diagnosed with cancer each year in New Jersey.

™ that according to projections, the cancer service line is increasing by 4% to 6% per year; the new center will be capable of handling up to 20,000 more cases per year. The number of staff available to assist patients in navigating care will be increased from 35 to 50 by the time the center opens in 2024, he said.

Libutti arrived after a period of transition following 2012 legislation that overhauled higher education governance and made the institute part of Rutgers University.

 At the time, restructuring was controversial, and some faculty left. Then part of the Robert Wood Johnson Medical School, CINJ already was producing world-class scientific results and collaborating with the state’s pharmaceutical sector on clinical trials.

Four years after Libutti’s arrival, predictions that reorganization could help make Rutgers CINJ a “powerhouse” appear to be coming true.

 Libutti has expanded the reach of the National Cancer Institute designation to cover the entire state as he has laid the groundwork for greater integration between the research and clinical programs and construction of a cancer center designed with patient experience as the focal point.

Patient experience is not a buzzword. Consumers increasingly select where they receive care based on experience ratings and patient reviews, and CMS’ patient experience ratings also factor into reimbursement.

 Therefore, getting patients to stay in New Jersey for cancer care is not enough, Libutti said.

When a patient arrives at Rutgers CINJ, every phase of treatment—including survivorship care—should be delivered seamlessly, he said. All treatment soon will be offered under one roof, without the need to cross town or change services. A bridge will connect the existing cancer center and hospital to the new pavilion. The relationship with the state’s largest health system will mean better coordination during emergencies, he continued.

“Having an integrated oncology service line across the many hospitals and facilities of RWJBarnabas Health [will mean] that even if a patient needs that kind of additional care, such as a visit to an emergency room hopefully they’re no more than 15 or 20 minutes away,” he said. “And now, you’re showing up in an emergency room in New Jersey. As is often the case, when there’s a side effect, if it’s a Saturday or it’s 10 o’clock on a Friday night, tracking down your physician or your records at a distant place is a challenge.”


Designed by HOK Healthcare, the Jack and Sheryl Morris Cancer Center will cover 510,000 square feet and have 84 infusion bays, which will increase capacity by one-third; the number of examination rooms will double to 74. There will be 96 inpatient beds on 3 floors, a dedicated floor for surgical and procedure rooms, wet-lab spaces for 10 research teams, and faculty offices.

 Advanced radiology services, diagnostic laboratories and equipment, a pharmacy, outpatient urgent care, and inpatient support spaces will be available in 1 location. Libutti is excited that existing services, such as a weekly tumor board that has met for years, will be able to better coordinate with other activities.

“The way I like to describe it is, rather than the patients going from doctor to doctor in a linear fashion, I think of the patient in the center of the lazy Susan [turntable] with all the physicians and necessary activities they have to undergo to get to a good diagnosis or to follow along during their care sort of circling around them,” he said. “And the patient is really the centerpiece of our care paradigm.”

Libutti worked closely with the developer, New Brunswick Development Corporation (DEVCO). Led by its president, Christopher J. Paladino, and its executive vice president, Sarah F. Clarke, DEVCO has reshaped the area in and around Rutgers’ New Brunswick campus, adding structures that include the honors college, New Brunswick’s performing arts center, and a hotel and conference center.

 The cancer center will stand out in the New Brunswick skyline and feature both indoor and outdoor common areas.

In an interview, Paladino said, “We’re really focused on making sure the public spaces are inviting, [that] they’re warm…as Dr Libutti described it, he wants the building to give everyone who walks in a virtual hug.”

The public might overlook the 25-foot-deep basement or the pavilion’s self-contained power plant, but these features will be achievements on their own. Clarke explained how sequencing will allow use of the garage to store materials as the tower is built. The deep basement will allow radiology services to be housed safely below ground; an earlier concept would have required above-ground concrete reinforcement. To avoid a feeling of darkness, the building will have a 4-story lobby that extends underground to allow natural light into the space.

Every project DEVCO completes offers insight into how people move through spaces, Paladino said. To design a cancer center, Libutti and the development team went straight to the sources as they conducted charettes that included physicians of different specialties, nurses, support staff, former patients, and caregivers. The groups initially received an early design overview from the architect, and then they went to work with markers and Post-It notes in hand.

“The natural thing was for this to turn into a ‘bitch’ session,” Paladino said, “but it very quickly became a ‘what if?’ session.” Paladino estimated that approximately 50 modifications came from this process, allowing the development team to catch problems early on. For example, Clarke has the gift of being able to identify materials that won’t last and finding aesthetically pleasing substitutes.

Paladino credits Libutti for his attention to the infusion center design, which went through multiple revisions until the team achieved the right balance of “privacy and openness.” 

Paladino brings personal experience to this project. His wife was treated for breast cancer many years ago, and the atmosphere of an infusion center remains familiar. “You get used to seeing certain people on your schedule. There was some level of camaraderie.” But on other days, patients don’t want company; rather than hanging curtains to give patients privacy, the Rutgers team decided that half walls with glass doors that open and close would be built.

As the pavilion rises, the team that will work in the new center continues to grow. Several high-profile hires have been announced, including Missak Haigentz Jr, MD, as chief of thoracic medical oncology and of head and neck medical oncology and clinical director for oncology integration; the latter role involves promoting patient safety and efficiency and improving value-based care, including screening and preventive services.

This integration will build upon what Libutti says is the center’s the team-based approach. “We have multidisciplinary teams focused on breast cancer, lung cancer, colon cancer, pancreas cancer, etc,” he said. “In terms of other specialists that are necessary in the context of caring for these patients, whether it be the appropriate diagnosis or providing supportive care, we have experts from a variety of disciplines, whether it be gastroenterologists, pathologists, or radiologists that all work together with our teams. That’s happening now and will continue to happen in the new cancer center.”


From the groundbreaking to the visit with Libutti, the phrase repeated is, “Cancer doesn’t travel well.” The aim to keep patients “15 to 20 minutes” from home is not arbitrary. Some patients will still seek cancer management in medical centers with greater fame in New York City, even though the burdens of travel are being recognized in the literature.

Longer travel times to a cancer center also may pose unanticipated consequences for payers:

For patients with pancreatic cancer, traveling more than 12.5 miles after surgery has been associated with worse overall survival.

Longer travel distance and insurance status helped determine which patients being treated for breast cancer were more likely to have contralateral prophylactic mastectomy; Black and Hispanic patients were at particular risk.

In a study of Medicare beneficiaries given a diagnosis of cancer, Medicare spending was 14% higher and patient cost responsibility was 10% greater among those traveling longer than 1 hour to a cancer center than for those having a travel time of 30 minutes or less.

Shorter travel times were related to higher hospitalization rates in the initial management stage, whereas longer travel times were related to a greater likelihood of hospitalization at the end of life.

Studies of patients with colorectal cancer and of surgery for prostate cancer found that longer travel times were associated with longer hospital stays.

Libutti said the issue of what excess travel does to patients with cancer is an area ripe for further study. “First off, there’s the expense;…for chemotherapy or radiation therapy, these are multiple visits a week and, certainly, many times per month in terms of travel,” he said. “That’s an expense not only in dollar expense for the travel itself, but time away from family, time away from work—you have a support system that’s critically important as you’re going through a cancer diagnosis. And that support system is turned upside down or at least on its side when you have to get your care at a distance.”

The realization that some patients from New Jersey need to drive 2 hours each way to New York City for every cancer treatment became real for Paladino and his wife when a traffic accident turned their typical 40-minute ride from their home outside Princeton into a trek spanning more than 2 hours.

As they reached valet parking for the appointment, Paladino said, he recalled his wife saying, “‘Just imagine if we had to do that every time.’ And that really struck home with me.” 


1. Cancer data and statistics. Centers for Disease Control and Prevention.  June 8, 2021. Accessed September 27, 2021. https://www.cdc.gov/cancer/dcpc/data/index.htm
2. RWJBarnabas Health and Rutgers Cancer Institute of New Jersey announce new $750 million state-of-the art freestanding cancer pavilion in New Brunswick. News release. June 3, 2019. Accessed September 27, 2021. https://bit.ly/3m5kdo8
3. Gov. Christie signs higher education restructuring bill. News12 New Jersey. August 22, 2018. Accessed September 30, 2021. https://newjersey.news12.com/gov-christie-signs-higher-education-restructuring-bill-34868881
4. Siegel J, Engelhardt KE, Hornor MA, Morgan KA, Lancaster WP. Travel distance and its interaction with patient and hospital factors in pancreas cancer care. Am J Surg. 2021;21(4):819-825. doi:10.1016/j.amjsurg.2020.08.023
5. Ward EP, Unkart JT, Bryant A, Murphy J, Blair SL. Influence of distance to hospital and insurance status on the rates of contralateral prophylactic mastectomy, a National Cancer Data Base study. Ann Surg Oncol. 2017;24:3038-3047. doi:10.1245/s10434-017-5985-1
6. Rocque GB, Williams CP, Miller HD, et al. Impact of travel time on health care costs and resource use by phase of care for older patients with cancer. J Clin Oncol. 2019;37(22):1935-1945. doi:10.1200/JCO.19.00175
7. Spaulding AC, Borkar S, Osagiede O, et al. Impact of travel distance on quality outcomes in colorectal cancer. Am J Manag Care. 2020;26(11):e347-e354. doi:10.37765/ajmc.2020.88529
8. Olson DJ, Gore JL, Daratha KB, Roberts KP. Travel burden and the direct medical costs of urologic surgery. J Health Econ Outcomes Res. 2016; 4(1);47-54. doi:10.36469/9825.
9. Rutgers Cancer Institute of New Jersey. National Cancer Institute. Updated February 10, 2021. Accessed September 28, 2021. https://www.cancer.gov/research/infrastructure/cancer-centers/find/cinj
10. NJ COVID latest: Thursday, June 24, 2021. PIX 11. June 24, 2021. Accessed September 30, 2021. https://pix11.com/news/coronavirus/nj-covidlatest-thursday-june-24-2021/
11. RWJ Barnabas Health and Rutgers Cancer Institute of New Jersey break ground on Jack & Sheryl Morris Cancer Center. News release. Rutgers Cancer Institute of New Jersey. June 24, 2021. Accessed September 26, 2021. https://bit.ly/39HXSHA
12. Evans T. Census 2020: New Jersey’s older and increasingly diverse centers are now leading the state’s population growth. New Jersey Future. September 13, 2021. Accessed September 26, 2021. https://bit.ly/3F0GHPS
13. Goldberg P. Libutti: how Rutgers Cancer Institute became a New Jersey-sized colossus. The Cancer Letter. May 17, 2019. Accessed September 27, 2021. https://bit.ly/3EYnDll
14. 2021 Healthcare Reputation report correlates strong reputation score with higher patient conversions on Google. News release. Reputation. March 4, 2021. Accessed September 27, 2021. https://bit.ly/2ZzQhsF
15. Detwiler K, Vaughn N. Patient satisfaction and HCAHPS reimbursement. Relias. September 11, 2020. Accessed September 28, 2021. https://www.relias.com/blog/how-do-patient-satisfaction-scores-affect-reimbursement
16. RWJBarnabas Health and Rutgers Cancer Institute of New Jersey unveil plans for new cancer pavilion. News release. HOK Healthcare. October 28, 2020. Accessed September 27, 2021. https://www.hok.com/news/2020-10/rwjbarnabas-health-and-rutgers-cancer-institute-ofnew-jersey-unveil-plans-for-new-cancer-pavilion/
17. About us. New Brunswick Development Corporation. Accessed September 27, 2021. https://devco.org/page/2/about-us
18. New chief of thoracic and head and neck medical oncology named to New Jersey’s only NCI designated comprehensive cancer center. News release. Rutgers Cancer Institute of New Jersey. September 1, 2021. Accessed September 27, 2021. https://www.cinj.org/new-chief-thoracic-and-headand-neck-medical-oncology-named-new-jerseys-only-nci-designated

COVER FEATURE

Building a Patient-Centered Cancer Center From the Ground Up

When the American Society of Clinical Oncology (ASCO) updated its policy statement on cancer disparities and health equity a year ago, 11 years had passed since the organization’s first statement on the differences in health care access, quality, and outcomes among patients of different races with cancer.

 The topic had become more timely in light of the inequity seen in COVID-19 mortality rates,

ongoing disparities in cancer care and outcomes,

 and other health metrics such as insurance status.

 Over the past year, the major oncology and hematology organizations—ASCO

, the Association of Community Cancer Centers (ACCC),

 the National Comprehensive Cancer Network,

—have issued statements, launched initiatives, or devoted portions of their national meetings to the issue of disparities in cancer care.

The ASCO authors concluded in 2020 that the time had come for less talk and more action “to overcome historical momentum and existing social structures responsible for disparate cancer outcomes,” and they put forth an action plan to improve diversity in hiring, clinical trials, access to care, and achieving “measurable and timely action toward achieving cancer health equity for all.”

In an article published ahead of her presidential address during the ASCO annual meeting in June, then–ASCO President Lori Pierce, MD, FASTRO, FASCO, discussed the organization’s commitment to Black patients with cancer, for whom inequities are especially glaring. In the United States, Black patients represent 15% of the cancer patient population, but they account for 4% to 6% of the enrollees in clinical trials.

 Black patients are 1.5 times more likely to be uninsured than White patients; only 3% of oncologists are Black, even though Black individuals make up 13% of the US population.

As a result, Pierce noted in a 2020 essay, “progress in cancer prevention, detection, and treatment has reduced overall mortality in the United States, but that progress has not been enjoyed by everyone. Poorer outcomes persist in Black men and women, in rural populations, and in patients with lower income and education.”

In addition, only 6% of US oncologists identify as Hispanic and few health investigators identify as non-White.

 Unlike non-Hispanic White individuals, for whom heart disease is the leading cause of death, cancer is the leading cause of death among Hispanic individuals.

All of this points to the need to reduce disparities, and quickly. But how? The ASCO authors found plenty of inertia in health care. 

™ gathered input from a group of health care leaders, from within and beyond the cancer community, and asked: How can we cancer disparities be reduced now? Specifically, the leaders were asked to discuss ideas that could be put into action in a 2-year time frame.

RANDALL A. OYER, MD
Medical Director, Oncology Program, Penn Medicine Lancaster General Health
Former President, Association of Community Cancer Centers
Lancaster, Pennsylvania

Use antibias training to ensure patients are invited to clinical trials

Randall A. Oyer, MD, discussed the need for more equitable clinical trials, a major initiative of ACCC. “Clinical trials are an indicator of quality of care,” he said. “Not all people have benefited to the same extent from the advances that have been made in cancer care in the United States. Health equity requires us to address the institutional racism and other failings that still exist [and their effect on populations].”

To begin to address these issues, Oyer said, “we need to get clinical trials out to where people live in the community.” First, this requires showing community practices how trials are set up and what personnel and resources are needed, Oyer said. Second, a near-term intervention would be to ensure that a broader group of patients are asked to take part in clinical trials, he said. “There’s still a lot of bias that’s involved in offering or not offering patients clinical trials, and we need to get training programs into the community to make sure that people understand their biases, so that we can mitigate those biases so that everyone is offered the opportunity to participate.”

A recent study found the most common reason patients don’t participate in a cancer clinical is because they are not asked, Oyer said.

 “If you ask a White patient, or you ask a Black patient, they both sign up, basically, to the same extent, if they’re offered the opportunity to do so.’’

In addition to these interventions, Oyer emphasized the need to “understand the social determinants of health and how they affect a patient’s health over their lifespan. [This includes] what kind of food, exercise, environment they live in, what kind of education for self-care, what kind of resources they have to access health care.”

Chief Medical Officer, AccessHope,
Duarte, California

Reduce disparities by leveraging lessons of telemedicine

AccessHope is a program that allows patients and community oncologists to tap into the expertise of City of Hope, often through electronic sharing of records so the patient does not have to travel.

 Todd M. Sachs, MD, called for increased education within the care delivery system, especially for patients. “That means getting out to various people where they live, where they work, where they spend their time,” he explained.

The increased use of telemedicine could also reduce disparities—COVID-19 revealed the potential for technology, Sachs noted. “We started to get to where people live, where they are,” he said.

Since the pandemic began, hospitals have  developed better protocols to ensure safety, Sachs said, but the risk is that the advantages seen with telemedicine could be lost. “I don’t want us to lose all that we gained by using telemedicine,” he said. 

With AccessHope, “we’re providing this high level of expertise and knowledge from physicians in Los Angeles to people who may not live in Los Angeles proper, who may live in South Dakota in a very rural area, or in Kansas in a rural area and are not able to be treated at a national cancer institute,” he said.

Technology is also important for sharing information and key to improving quality, another way to reduce disparities in cancer care. “Cancer is different. In the world of cancer, there’s so much change for the better,” Sachs said. “New treatments, new therapies, new protocols, new research—if you’re an oncologist today and you’re trying to remember and learn and read all of those changes for over 100 types of cancer, it’s too hard to do.” 

Finally, he said, “we need people to go in and get their preventive care. That would be a big win, and that can happen, ASAP. We don’t have to wait 2 years for that.”

Clinical Executive Director, AccessHope
Associate Clinical Professor, Department of Medical Oncology and Therapeutics
Research, City of Hope
Duarte, California

Level the playing field to reduce variability in cancer care

Similarly, H. Jack West, MD, called for bringing more specialized access to more patients. West, a lung cancer specialist, said he founded the Global Resource for Advancing Cancer Education (GRACE) with the intention of being able “to help close the gap between the best care that’s available for some people and what people actually get.” GRACE was created in response to issues with quality of care outside academic settings. “There is an unfortunate shortfall and inequity in the broader community; it’s just quite variable. Not to say that there aren’t general oncologists who do a sensational job, but it’s really hard to keep up with everything that happens, especially in the past 5 or 10 years.”

The volume of data being published and the pace of advances in care have escalated to the point, “where it’s not feasible to expect one doctor, any doctor, to know everything that’s out there or even enough to necessarily be strongly competent in a broad range of oncology,” he said. West’s mission is to “level the playing field and make it possible for people who don’t have access to a specialist to borrow their expertise on demand by uploading it free for everybody.”

An additional benefit of GRACE is that it allows information to be democratized by enabling patients to be educated about their condition. West described it this way: “If I had a conversation with a patient that would be great for the patient, it would just evaporate into the room. But if I uploaded the information that I shared with them and made it available to people through a blog, anybody anywhere could access it—and it wasn’t any more work for me, but maybe it would help them have a conversation with their doctor.”

The idea, he continued, is this: “As long as 1 person in that exam room knows the best treatment, that’s fine—even if that’s the patient.”

Patient education is important, West said, but it can’t consume all of a physician’s time. West emphasized, however, that “if you make that information available to patients, they can be unbelievably laserlike-focused on finding the best information available anywhere.”

Executive Director, Mays Cancer Center
UT Health San Antonio MD Anderson Cancer Center
San Antonio, Texas

Include the family health expert in all key discussions

Mesa emphasized the importance of working to achieve more effective and equitable clinical trial access as a means of improving health care access and quality. He brought attention to the need for inclusive research. “The key goal is, do the innovations going on in your clinical trials reflect the people in your city and region, I mean—the people you’re serving? We all recognize that there’s tremendous diversity within diversity.”

In addition to having representative demographics in a trial. Mesa also pointed out the need to understand the diversity found within diverse groups, stating, “We clearly have learned and are studying the great differences [among] even Latino populations. There are differences between individuals that have migrated from Mexico recently [and] individuals [who] are of Mexican heritage, but their families have been in the states for a long period of time; individuals from the Caribbean, people like me who are Cuban, [or individuals from] South America. So, there’s a lot of diversity, and there’s diversity as it relates to genetics, culture, and other parts.”

Those who run clinical trials must also address “logistics, access, sometimes transportation, sometimes other barriers,” he said. “The intensity of participating in the trial, in terms of time away from work” can affect who ends up participating, Mesa explained. If the trial schedule “makes it much more difficult to be able to either leave work, to be allowed to leave work, or to not paid for leaving work, that can really influence things,” he said.

Another focus of Mesa’s is improving health literacy and trust in patient communities. One method Mesa said has been helpful with patients with cancer in south Texas is to include the family health expert in key discussions. This could be a family member employed in health care, anyone “from a phlebotomist at a local hospital to a pharmacy technician at CVS, or a physician or a nurse,” he said. This is a person the family trusts to discuss treatment options, including clinical trials.

SACHIN H. JAIN, MD, MBA, FACP
President and CEO, SCAN Group and SCAN Health Plan
Long Beach, California

Uncover barriers to care and underlying causes to health issues

Sachin H. Jain, MD, MBA, FACP, is a pioneer at finding the root causes of why individuals use too much unnecessary health care—such as hospitalizations—and coming up with better ways to pay for care individuals really need. Before the COVID-19 pandemic, when he worked for CareMore, Jain created programs to treat loneliness as a health issue.

These days, he’s taking on homelessness by working on a payment model to address a crisis that has exploded in California,15 where he’s has been based since 2015. 

“We have a lot of unnecessary health care utilization that’s driven by poorly managed chronic disease. And if you actually apply that frame to multiple different populations, you find key areas where you can improve health care outcomes and reduce overall health care spending and utilization,” Jain said. “That’s why we look at things like homelessness, and we ask ‘What is the underlying issue there that we can address and leverage to reduce overall health care costs and improve health care outcomes for patients?’”

By addressing these social determinants, Jain argues, we can potentially “contract the hospital sector. Because ultimately, what we’re trying to do is make hospital care less necessary by better managing people’s conditions.”

Doing so requires moving away from a fee-for-service model. “We actually have lots of data on who the so-called rising-risk or high-risk patients are, but the capacity in the health care system to actually act on those high-risk or rising-risk patients is low because of how we pay for care—and because of how we actually structured and organized care delivery. Because we largely have a fee-for-service chassis, we mostly take care of people when they have problems, as opposed to paying significantly for upstream management and prevention.”

When asked how soon this move away from fee-for-service care delivery could be applied, Jain said, “I see medical groups in California—and, really, all over the country—that are starting to embrace this way of thinking about patient care. And they’re changing how they work as a result of changes and how they’ve decided to get paid by third-party payers.”

Jain warns that the transition brings a measure of risk. “There is an opportunity to simultaneously improve the quality of care, but there’s also potentially an erosion of the quality of care if we don’t manage that carefully,” he said.


Discussions with each expert confirmed that the United States still has a long way to go to achieve equity in health care. Hospitals, health care systems, and clinical trials have not fully addressed the historic barriers to access or the social factors that produce uneven outcomes. Yet, as the interviews showed, solutions are possible. Each one proposed ideas based on concrete and successful plans that have been implemented, including strategies the interviewees had used in their own fields.
Although the pandemic has raised the visibility of how unequally health care is delivered, it has also been a catalyst for many providers to offer increasingly creative solutions that more effectively address disparities. As such, it is important to seize this moment and move forward with a renewed sense of urgency so that the momentum can lead to effective and sustainable transformation of how care is delivered. 


1. Patel MI, Lopez AM, Blackstock W. Cancer disparities and health equity: a policy statement from the American Society of Clinical Oncology. J Clin Oncol. 2020;38(29):3429-3448. doi:10.1200/JCO.20.00642

2. Goss E, Lopez AM, Brown CL, Wollins DS, Brawley OW, Raghaven D. American Society of Clinical Oncology policy statement: disparities in cancer care. J Clin Oncol. 2009;27(17):2881-2885. doi:10.1200/JCO.2008.21.1680

3. Health disparities. Provisional death counts for coronavirus disease 2019 (COVID-19). CDC. Updated September 29, 2021. Accessed September 30, 2021. https://www.cdc.gov/nchs/nvss/vsrr/covid19/health_disparities.htm

4. Balogun OD, Bea VJ, Phillips E. Disparities in cancer outcomes due to COVID-19-a tale of 2 cities. JAMA Oncol. 2020;6(10):1531-1532. doi:10.1001/jamaoncol.2020.3327

5. Artiga S, Hill L, Orgera K, Damico A. Health coverage by race and ethnicity, 2010-2019. Kaiser Family Foundation. July 16, 2021. Accessed September 26, 2021. https://www.kff.org/racial-equity-and-health-policy/issue-brief/health-coverage-by-race-and-ethnicity/

6. Association of Community Cancer Centers launches institute to diversify cancer clinical trials. ACCC. News release. June 3, 2021. Accessed September 26, 2021. https://www.accc-cancer.org/home/news-media/press-releases/news-template/2021/06/04/association-of-community-cancer-centers-launches-institute-to-diversify-cancer-clinical-trials

7. Elevating cancer equity: recommendations to reduce racial disparities in guideline adherent cancer care. National Comprehensive Cancer Network. February 22, 2021. Accessed September 30, 2021. https://www.nccn.org/docs/default-source/oncology-policy-program/2021_elevating_
cancer_equity_webinar_slides.pdf?sfvrsn=e11f66e4_2

8. Flowers CR, Donald CE. A look into ASH’s diversity, equity, and inclusion efforts. The Hematologist. 2021;18(2). February 19, 2021. Accessed September 26, 2021. https://ashpublications.org/thehematologist/article/475281/A-Look-Into-ASH-s-Diversity-Equity-and-Inclusion

9. Community Oncology Alliance. COA disparities in cancer care position statement. April 30, 2021. Accessed September 30, 2021. https://communityoncology.org/coa-disparities-in-cancer-care-position-statement/

10. Pierce L. ASCO’s commitment to addressing equity, diversity and
inclusion of Black cancer patients and survivors. JCO Oncol Pract.
2021;17(5):255-257. doi:10.1200/OP.21.00257

11. American Cancer Society. Cancer Facts and Figures for Hispanics/Latinos, 2018-2020. Atlanta; American Cancer Society, 2018.

12. Alhajji M, Bass SB, Nicholson A, et al. Comparing perceptions and decisional conflict towards participation in cancer clinical trials among African American patients who have and have not participated. J Cancer Educ. Published online July 11, 2020. doi:10.1007/s13187-020-01827-w

13. Caffrey M, Levine H. Reimagining cancer care delivery-and serving employers-
through AccessHope. Am J Manag Care. 2020;26(SP10):SP365-
SP366. doi:10.37765/ajmc.2020.88558

14. Caruso R. CareMore’s Togetherness program addresses a symptom of living with chronic illness: loneliness. Am J Manag Care. 2018;24(SP10):SP442.

15. Jain SH. Homelessness is a healthcare issue. Why don’t we treat it as one? Forbes. April 17, 2021. Accessed September 20, 2021. https://www.forbes.com/sites/sachinjain/2021/04/17/homelessness-is-a-healthcare-issuewhy-dont-we-treat-it-as-one/?sh=4c9dfcd777e3

Addressing Disparities in Cancer Care and Beyond: What Can Be Done Now?

 Therapeutics) is currently being investigated for use against mesothelin overexpression in 4 types of solid tumor cancers: malignant mesothelioma, ovarian cancer, cholangiocarcinoma, and non–small cell lung cancer (NSCLC). Data, first presented at this year’s American Association of Cancer Research (AACR) annual meeting, showed a single intravenous (IV) infusion of the engineered cellular therapy produced a 100% disease control rate (DCR) and 61% target lesion regression rate (TLR) in 7 evaluable patients: 6 with malignant mesothelioma and 1, ovarian cancer.

In an update presented at European Society for Medical Oncology 2021 Congress, from the phase 1/2 dose-escalation trial examining gavo-cel, data were presented on 17 patients evaluated for safety—12 with malignant mesothelioma, 4 with ovarian cancer, and 1 with cholangiocarcinoma—all of whom again received a single IV gavo-cel infusion (16 patients were evaluated for efficacy). Results were still robust for both measures, but lower: 92% and 24%, respectively.

), lead author David S. Hong, MD, professor and deputy director, Department of Investigational Cancer Therapeutics, and associate vice president of clinical research, The University of Texas MD Anderson Cancer Center, discussed these newest data, why mesothelin is such an attractive target for precision treatment, and next steps in the gavo-cel investigation.

This interview has been edited slightly for conciseness and clarity. 

Phase 1 data on gavo-cel were presented in April at the AACR annual meeting. With this interim update of phase 1/2 data presented at ESMO Congress 2021, will you tell us about the dose-escalation results you have seen and how they build on previous findings?

 A couple of things. This is an expansion of what we presented in April—we now have 16 evaluable patients on the trial—at that time, the overall response rate was about 50%. 

The overall investigator response rate now, by the independent group, is around 38% have a confirmed response rate. So, some difference. We expect that there’s going to be some decrease in the actual response rate as you expand these studies, but still a very robust response rate in this really heavily pretreated patient population of mesothelioma, ovarian cancer, and cholangiocarcinoma.

The overall toxicity profile has not really significantly changed from what we saw in April. Overall, it’s a very encouraging study. We’ll see as we go into the expansion, and see more patients, if we can maintain that really robust response rate. We’re really encouraged by that.

 Can you explain the process behind delivering gavo-cel, particularly the use of an antimesothelin antibody lentiviral vector, as well as why lentiviral vectors are an appropriate vehicle for anticancer gene therapies?

I think mesothelin is a unique target. There are very few antigens that you can target, independent of human leukocyte antigen, that are, to a large extent, expressed on tumors and have very or limited expression on normal tissue. We know that mesothelin is highly expressed, obviously in malignant mesothelioma, but it’s also expressed in a number of very common tumor types: NSCLC, cholangiocarcinoma, and ovarian cancer. Even to some extent, pancreatic cancer. So I think that was the reason that they used mesothelin as a target.

Gavo-cel is a unique platform. CAR Ts [chimeric antigen receptor T cells], in and of themselves, have not shown a whole lot of activity in solid tumors. We obviously know the success of CD19-based cellular therapies and CAR T in lymphomas and leukemias, but if you look at some of the cellular therapies that have been in existence for many, many years, CAR Ts have not been gangbusters. There’s not an approved cellular therapy right now in solid tumors. But TCRs [T-cell receptors] seem to have more robust activity in solid tumors, and there’s a lot of different reasons for that.

 Therapeutics—is trying to take the advantage of TCRs, relatives of CAR Ts. They reengineer these T cells, really to bind the epsilon chain of these TCR receptors that then can be called HLA independent yet bind mesothelin, which is damaged and obviously that is overexpressed in a lot of tumors. 

Why lentiviral vectors? I think, to a large extent, partly because that technology has probably been validated most with many of the different ways that we are constructing these platforms with these cellular therapies. That’s been just the most straightforward way to do it. I know there are other technologies trying to look at that, but I think that’s to a large extent why that’s been implemented: because it’s been something that’s been proven.

: Is overexpression of mesothelin the singular fact that that contributes to gavo-cel’s success against solid tumor or are there other reasons?

There’s a threshold we have to meet for these patients to be on the trial. The numbers are small—16 evaluable patients. The analysis that we’ve done so far, it’s too early for us to tell if you have 100% mesothelin expression, you’re going to have a better response than if you had 30% mesothelin expression, for example. That makes sense. But there have been other cellular therapies, other than mesothelin, where the nuances of whether a patient responds, based upon antigen expression, really hasn’t panned out. I suspect there are lots of different variables that we’re still trying to figure out, whether it’s overexpression level, whether these cells persist in the body. 

There are probably other factors that we haven’t identified that may kind of tweak which patients may actually benefit vs not. I do think that we will figure those things out, that those things will eventually emerge, and maybe even to the point where TCR

 or any other companies that decide to move into larger phase 3 trials, we’ll figure that out. But right now it’s not really clear whether or not just expression in itself is the main driver for response.

 How does lymphodepletion contribute to precision oncology treatment success?

In general, we use lymphodepletion just like we use an autologous bone marrow transplantation: to allow for continued survival in that host body. This trial is interesting. The FDA required the first patient to not get lymphodepletion as we were escalating. And then following that, after a period of time the following patients had to be lymphodepleted. Interestingly enough, we saw some tumor regression independent of lymphodepletion. Clearly, those patients who had had lymphodepletion responded well, and that’s probably because the cells were able to evade the natural immune system better with lymphodepletion and were able to persist in the body longer because of lymphodepletion. That’s the primary reason why we do lymphodepletion, in general.

These data also address an additional indication for gavo-cel, in cholangiocarcinoma. What do the 3 solid tumor cancer types for which use of gavo-cel is being investigated—mesothelioma and ovarian cancer, as well—have in common that make them appropriate targets for treatment with gavo-cel?

They all expressed mesothelin. Obviously, mesothelin is highly expressed in mesothelioma. Interestingly enough, also in ovarian cancer and cholangiocarcinoma—not to the extent that mesothelioma patients have it, but a fairly high percentage of ovarian cancer and cholangiocarcinoma patients have high expression of mesothelin. So that’s to a large extent why we chose those patients. There’s a prescreening process that occurs with all of these patients, and the reason we narrowed this is so that we’re not prescreening 1000 patients and you get 1 patient out of it. You want to prescreen patients that you think are going to have high expression of mesothelin. So that’s why we chose ovarian, cholangiocarcinoma, and mesotheliomas.

 Do patients need to have exhausted all previous treatment options or could gavo-cel eventually be a first-line choice?

: That’s a question that is hard to answer right now. I think, in general, patients who have had less prior therapies will eventually do better with immunotherapy. We know that with checkpoint inhibitors. I think that may pan out for other cellular therapies, too, whether gavo-cel or other patients. Just how drug development works, as you all know, these patients have frontline options that we know have survival benefit; particularly in many of these types of tumors, it’s standard chemotherapy. My guess is that if gavo-cel continues to show this robust response, it’s a high indication that it will likely work in the refractory setting and there’s a good chance that it will work as you go up the lines of prior therapy, where at some point we may be able to compare this with standard-line therapy. But I think that it’s just way too early for us to know right now.

 The fourth investigative indication for gavo-cel is NSCLC. Overall, lung cancer is notoriously diagnosed at advanced stages because the symptoms often mask other conditions. In this regard, is a precision treatment such gavo-cel meant to be curative or improve quality of life for the remaining time a patient may have?

 Right now, it’s a phase 1 study. I think the hope is that all cellular therapies down the line will lead toward…at least prolonged remission and prolonged benefit in these patients, like NSCLC. I don’t think right now we are under any illusion that this is going to lead to cures right now in NSCLC refractory to immunotherapy and chemotherapy. But if response rates pan out as we have seen in mesothelioma and ovarian cancer, I do think that there’s a good chance that there will be a benefit in chemorefractory NSCLC. In many of the patients that we did treat with gavo-cel who did respond, they were refractory already to checkpoint inhibitor therapy. Most patients with NSCLC will have received some kind of checkpoint inhibitor therapy.

As of the report of the 16 patients, we did not include any NSCLC patients as I recall, but I don’t see why we couldn’t see similar benefit in those patients.

: Will you be looking at gavo-cel in a larger cohort?

 We’re almost at the recommended phase 2 dose. I think we’re going to launch, once we do expansion, an amend to this as a phase 2 portion in each of these different tumor types. There are a number of other combinations that we’re going to look at down the line, whether it’s with  checkpoint inhibitors or with other possible combinations that hopefully would augment these cells. I’m sure we’re going to try to present something next year, maybe an update to this, but also maybe share additional data on combinations.

I just want to say that cellular therapy in solid tumors is an exciting area that is eventually going to emerge, like checkpoint inhibitors in solid tumors. The technologies still have a long way to go, but I think what’s exciting is these technologies can be tweaked. We are learning every day. Every patient we put on we try to understand why that patient responded vs not, why those patients have certain toxicities vs not. And I think we’ll learn.

Also, just the people I’ve met, not only at TCR

, but other companies, they are just brilliant. I take care of the patients and help design the clinical trials, but the people who actually developed this technology are some of the brightest people I’ve met. I’m optimistic that we will find that this fact these kinds of platforms and these cellular therapies will work in patients and in our cancer patients. And hopefully we’ll be able to scale it so that community physicians and other physicians can give it just like I give it in MD Anderson.


1. Hong DS, Johnson M, Tanyi JL, et al. Preliminary safety and efficacy of gavocabtagene autoleucel (gavo-cel, TC-210), a T cell receptor fusion construct (TRuC), in patients with treatment refractory mesothelin overexpressing solid tumors. Presented at: AACR Annual Meeting; April 10-15 and May 17-21, 2021. Abstract CT105.
2. Hong DS, Johnson M, Tanyi JL, et al. Gavocabtagene autoleucel (gavo-cel, TC-210) dose escalation in refractory mesothelin-expressing solid tumors. Presented at: ESMO Congress 2021; September 16-21, 2021. Poster 9590. https://bit.ly/39T1czF

Dr David S. Hong: We Are Learning Every Day About Cellular Therapies

™’s summer interviews with experts on diffuse large B-cell lymphoma (DLBCL) is with Alan Skarbnik, MD, director of the Lymphoma and Chronic Lymphocytic Leukemia (CLL) program and director of the Experimental Therapeutic and Immune Effector Cell Program at Novant Health Cancer Institute in Charlotte, North Carolina.

In May, Skarbnik was lead author of an article on phase 1b results on safety and clinical effects of combining checkpoint inhibition therapy (ipilimumab and nivolumab) after autologous stem cell transplant (ASCT)

 for patients with high-risk DLBCL, mature T-cell lymphoma, and multiple myeloma. Although the cohorts were small and Skarbnik describes the findings as “hypothesis driving,” progression-free survival (PFS) and overall survival (OS) at 18 months post-ASCT were highest in the primary refractory DLBCL cohorts, at 85% and 100%, respectively. In relapsed DLBCL, the results were not as promising: PFS was 28.6% and OS was 57.1%.

As Skarbnik explains, the phase 1b study (NCT02681302) was planned before the first chimeric antigen receptor (CAR) T-cell therapies were approved—but it informs the bottom line being reported today: immunotherapy approaches in primary refractory DLBCL may be superior to cytotoxic chemotherapy with transplant.

This interview has been edited for length and clarity.

In May, you published results involving the use of combined checkpoint inhibitors following ASCT in DLBCL and other conditions. Can you discuss the overall findings?

 The study first [sought] to evaluate the safety of this approach, using combined checkpoint inhibitors, nivolumab and ipilimumab, immediately following autologous stem cell transplantation. That combination had not been used before in that specific setting, and we wanted to evaluate whether it was safe and feasible The second end point investigated outcomes, particularly in terms of PFS and OS. For patients with high-risk, multiple hematologic malignancies, there were different cohorts. We had 1 cohort for patients with primary refractory DLBCL and a cohort for patients who had early relapse DLBCL within the first year after frontline treatment.

We had 2 cohorts for T-cell lymphoma: 1 for advanced stage frontline consolidation, the other for relapse or refractory peripheral T-cell lymphoma. We excluded ALK-positive anaplastic large cell lymphoma from this cohort because we know they have better outcomes. Then we had 2 myeloma cohorts: 1 for high-risk multiple myeloma by cytogenetics as frontline consolidation and the other for myeloma that relapsed within 3 years of an up-front transplant—so [this would] be a second transplant with the checkpoint inhibitor consolidation.

In this study, we did not identify any new safety signals, when compared with previous studies—these drugs are largely used in solid tumors—for lung, for renal cancer and melanoma. The adverse effects [AEs] were largely immune-related and were treated with steroids. We saw more cytopenias with these agents than in other settings, but cytopenias are very common following transplantation, so there’s a confounding factor.

What about efficacy in DLBCL? What differences did you observe?

 Efficacy seems to be largely dependent on the disease state we used it for; this is a phase 1 study, and is mainly hypothesis driving. Cohorts had small numbers; each cohort had 7 patients, except for the T-cell cohorts, that were closed early due to slow accrual. The cohort of primary refractory DLBCL had 7 patients. Most of them were not in complete remission after 2nd line therapy before undergoing transplant. Patients were allowed enrollment in the trial with active disease as long as there was no progression through the previous line of salvage therapy. We allowed for stable disease or partial responses to the most recent salvage therapy. Most of the patients had a partial response in that cohort, and all the patients presented with complete response after transplant and checkpoint inhibitor consolidation.

Of the 7 patients, only 1 patient presented progression of disease in a small lymph node. The patient was treated with radiation therapy and rituximab, entered remission again and is still in remission. All other patients remain progression and disease free, and it’s been over 3 years of follow-up.

This is a disease state where the median overall survival after transplant is close to 14 months. Again, it’s hard to compare different trials, particularly in a very small population. But it raises a question: Is it a reasonable and efficacious approach? It will take a larger trial to confirm that.

However, in the cohort of patients with DLBCL that achieved a complete remission and then presented relapse within the first year—which was the second cohort of DLBCL—we didn’t see similar outcomes. At 18 months, the PFS was 28.6% and OS was 57%. So there’s a potentially different efficacy signal there. We’re not sure why that happened. It could be because there were small numbers and this difference is random. It could be that there are actual biological differences in the disease states. What we tried to accomplish with this approach was to skew the post-transplant immune reconstitution toward an effector phenotype rather than a tolerance phenotype, by using checkpoint inhibitors.

Usually, after autologous stem cell transplantation the first immune cells to recover are regulatory T cells, which may hinder an effective immune response against cancer. By using this combination, we tried to flip that and increase the T effector component to allow for an anti-cancer immunologic effect. We observed differences in the immunologic profiles between the two DLBCL cohorts, using this approach. In the primary refractory DLBCL cohort, the regulatory T-cells remained low for 18 weeks following transplantation, with a corresponding early increase in the effector T-cell population. 

In the early-relapsed DLBCL cohort, there was no significant decrease in the regulatory T-cell component and the effector T-cells remained low until 12 weeks post transplant. These differences may explain the contrasting outcomes between those two cohorts.

Even if it’s small numbers, though, you’ve simultaneously addressed all the big issues that come up in DLBCL. Patients relapse—and what is the right therapy once the relapse happens? What’s the right sequence when there are so many choices? Once there is a transplant, what comes next? You’ve looked at a lot of those challenges. 

Yes, we did. Let me remind you that when the study was written and started, CAR T cells weren’t approved. We started writing the study in 2015, and the study started in 2016 before the commercial approval of CAR T cells.

I think what’s clear to the lymphoma community is that for patients who present primary refractory disease and/or early relapse of disease—especially within the first 6 to 12 months following frontline therapy—chemotherapy is not the answer. The disease has shown its face and it doesn’t generally respond to more chemotherapy. It’s different than a disease that comes 2 years later or even more than a year later, where you do have still a chance to salvage those patients and then consolidate with autologous stem cell transplantation. We know that stem cell transplantation on its own is basically very high-dose chemotherapy—the stem cell transplant is a rescue for the myelotoxicity that the chemotherapy causes. There’s a minimal immunologic effect for a very short period after recovery, but that’s it.

We’ve seen with the CAR T experience—there have been press releases, but we don’t have all the data yet—that in 2 trials [NCT03391466; NCT03575351] comparing chemotherapy and transplant vs CAR T

in the second-line setting for patients with primary refractory [and] early relapse disease [that] there’s superiority in terms of event-free survival in [the CAR T] patients.

The experience in the past show that it’s very hard to treat primary refractory DLBCL. The option we had before was to take the patient to transplant with potential residual disease after salvage, and those are the patients who generally end up presenting a relapse. So, the idea of the [phase 1] trial was to shift that perspective and include some immunotherapy in the fold to improve on efficacy. It is a different process, but to some extent it is the same idea behind CAR T-cell therapy—using an immunologic approach rather than a purely cytotoxic chemotherapy approach.

As of today, we don’t yet know what’s the ideal process for treating these patients. Fortunately, we have more options coming on board. There are bispecific antibodies that are being studied for DLBCL; I think they are going to have a very strong place in the treatment of patients with refractory or early relapse disease. We need to go beyond cytotoxic chemotherapy for primary refractory disease, and evaluate immunotherapy beyond rituximab.

 In terms of the approach [in this study], you’ve ried some of the more standard immunotherapy—we’ve had CAR T come online, we’ve had [tafasitamab] come online. Would you try these therapies?

 I’m a big fan of CAR T cells. I think CAR T cells in the second-line setting may be very reasonable; there’s a good rationale for that but we need to wait for the complete dataset from the studies comparing CAR T with autologous stem cell transplant in second line to draw conclusions. It seems that the earlier you use these therapies, when you have less T cell exhaustion, they may be more effective in driving responses. Once patients have seen 3 or 4 lines of chemotherapy, T cells are likely to be more exhausted.

In terms of logistics, CAR T cell therapy is certainly easier than this approach that we studied. First, there’s the transplant and then there are almost 6 months of consolidation with immunotherapy using an intensive schedule.

There are new agents coming on board. Tafasitamab is approved; we have loncastuximab tesirine approved, which is an antibody-drug conjugate that also targets CD19. We do have CAR T, which is likely to come to second line in the very near future, and have the bispecific [antibodies], with ongoing studies for DLBCL. Again, I think the point to make is that an immunologic approach for primary refractory or early relapsed DLBCL seems more promising than the traditional cytotoxic 
chemotherapy approach with stem cell transplant. 

1. Skarbnik AP, Donato ML, Feinman R, et al. Safety and efficacy of consolidation therapy with ipilimumab plus nivolumab after autologous stem cell transplantation. Transplant Cell Ther. 2021;27(5):391-403. doi:10.1016/j.jtct.2020.12.026.
2. Kite announces Yescarta CAR T-cell therapy improved event-free survival by 60% over chemotherapy plus stem cell transplant in second-line relapsed or refractory large B-cell lymphoma. News release. Gilead. June 28, 2021. Accessed September 16, 2021. https://bit.ly/3zbZOSU
3. Bristol Myers Squibb announces positive topline results from phase 3 TRANSFORM trial evaluating Breyanzi (lisocabtagene maraleucel) versus chemotherapy followed by stem cell transplant in second-line relapsed or refractory large B-cell lymphoma. News release.
Bristol Myers Squibb. June 10, 2021. Accessed September 16, 2021. https://bit.ly/2VPLvWA

Conversations on CAR T: Study of Checkpoint Inhibitors After Transplant Bolsters Case for CAR T, Skarbnik Says

) conducted in-depth interviews with experts on current research and practice in chimeric antigen receptor (CAR) T-cell therapy, including opportunities and challenges in academic and community settings. This interview is with Amitkumar Mehta, MD, director of the Lymphoma Program and Immune Effector Cell/CAR T Program and an associate professor at the University of Alabama at Birmingham (UAB). Mehta discussed a review paper he coauthored that appeared in 

which raised the issue of financial toxicity that many patients face. He also discussed the development of markers to gauge who can safely receive outpatient CAR T-cell therapy and why he advises his patients to keep wearing their masks.

The interview has been edited for length and clarity.

Let’s discuss the review paper on CAR T-cell therapy published in June. One idea you present is the concept of universal CARs. Can you elaborate?

 If you look at CAR T treatment, it is one of the best for relapsed diffuse large B-cell lymphoma (DLBCL)—it has definitely changed the treatment paradigm. If patients have the first
relapse—whether [they are] transplant eligible or not or…high-dose chemotherapy eligible or not, based on their comorbidities and performance status—once they cross the second-line therapy
and the third-line therapy everybody looks at the care team: are all patients able to go to CAR T? The answer is no. There are a variety of reasons, including the distance from the academic center, because most CAR T treatments are offered at academic centers or large community-based practices. So if the doctor’s practice is in rural Alabama, the patient must travel all the way to the academic center to get CAR T therapy. That’s one factor.

Another is insurance—it’s a big challenge. The third is that this disease is aggressive; patients progress very fast. We have very limited time for factors like insurance approval and for doing some of the testing before pursuing CAR T, or for the case-based agreement that the institutions have to do with the insurance company. These are all limiting factors for offering this life-saving treatment for patients.

So how can we make it universal? That was my concept––whether we can bring it to the community centers, where we can have a concept of a formal partnership in which academia can create teams that…offer treatment locally or closest to the patient, or whether we can have off-the-shelf CAR T, where the patients don’t have to wait for the preparation time, which ranges from 2 weeks to 6 weeks depending on which product you’re using. 

Also, off-the-shelf CAR T reduces the preparation time as well as availability. So, if I…have a patient who has to go for a treatment, I say, “Well, I’m going to prescribe this, which will be available next week,” compared to 6 weeks from now. Those factors will make this treatment universal.

Other subtle factors that come in are to do with biomarkers, such as a biomarker-driven prediction as to whether this patient will develop toxicities like cytokine release syndrome or neurotoxicity,
or whether this patient will respond or not. That way we can predict the outcome of not only the toxicity but also the efficacy of treatment.

 How close are we to getting allogenic or “off the shelf” treatment? It has been discussed for a while now. Are we getting closer?

At the American Society of Clinical Oncology there were a few phase 1 studies published, and they are being expanded. At the [December American Society of Hematology] meeting we’ll have further updates. There are a few therapies—I would put them in the cellular therapy category— and one is definitely CAR T. A second is CAR-NK (natural killer), where we are transfecting these NK cells. The third emerging therapy is activated NK cells…and they are being combined with other CD-20– or CD-19–directed therapies to see how the outcomes are. The activated NK and T-cell therapies have been used in Epstein-Barr virus (EBV)-driven lymphomas and EBV-driven malignancies before. So it’s not just CAR T, but we are also looking at other ways to expand the cellular therapy offering to lymphoma patients. It will be very exciting in the next 3 to 5 years when we might have some of this approved. 

These treatments do come with adverse effects, so if you have allogenic cellular therapy—just like allogenic transplant—we may have to look at the additional toxicities in terms of graft-vs-host disease. Apart from the toxicities that we see with autologous CAR T cells, where the patient’s T cells are transfected…, there could be an added adverse effect of graft-vs-host disease, which may have a longer or shorter duration.

You have discussed the challenges you’re having with finding biomarkers to identify the patients who are at risk for toxic effects. How far away are we from having really good biomarkers so we can stratify patients?

We still don’t have any biomarkers, but there are some indirect indicators that we can discuss. One of them is how bulky the disease is, whether the patient’s lactate dehydrogenase is
elevated right from the beginning or whether the patient has elevated ferritin or C-reactive protein levels. That can tell us that these patients may develop more cytokine release syndrome or the neurotoxicity syndrome. Hopefully, in a couple of years, we might have a predictive index to tell us “this patient could develop cytokine release syndrome” or “the patient will have higher chances compared with other patients.”

Why is this important? Of course, it is very important for the safety of the patients. But another aspect is very key, which many of the payers might be interested in, especially at institutions such as mine where we have rolled out an outpatient CAR T program. We want to make sure that those who are outpatients are at low risk of developing cytokine release syndrome and the neurotoxicity. If we can manage them as outpatients, the patient doesn’t have to go in the hospital for 7 to 10 days.

Why is it critical at this point? Because of the COVID-19 pandemic. As you know, the Delta variant cases are rapidly rising; hospital beds are full with those patients. Therefore if I have to plan for a CAR T patient, and if I say I need 7 to 10 days for an inpatient bed, the hospital administration will look at me and say, “You know, it may not be possible.”

So if we can we avoid those kinds of challenges, based on predictive markers that show a patient is low risk, we can treat a patient as an outpatient instead of admitting him. The other factor from a payer perspective is whether there is a change in the incentive model. With outpatient regimens and treatments they’re paid differently compared to inpatient, and most of the inpatient regimens, as you know, are way more expensive for both the hospital and the payer. If you have a predictive marker and an index that can say this patient is low risk, and we can treat them on an outpatient basis, there may be a huge difference in finances compared with a patient who is treated as an inpatient. So those factors are very critical. And I am very positive that based on the markers we’re looking at we will come up with some type of index in the next couple of years.

Speaking of COVID-19, how are you handling patients with DLBCL and vaccination? Have you
developed a set of protocols in terms of timing, vaccination, and treatment?

 For most of my patients on therapy, I ask them to get vaccinated. If you look at the recent
CDC recommendations, they’re suggesting a booster for immunocompromised patients. If I’m
starting any patient on new treatment, I’m highly recommending that they get the vaccine before they start the treatment. They’re immunocompetent right now, so they can impart an immune response. That way they are protected. As with other immunocompetent people, if they’re on the therapy and they have not received the vaccine, I asked them to get vaccinated at the earliest opportunity. And that can happen during the time where their counts are coming up so that they can get the vaccine. But I do know that if they’re on the treatment, or within a few months after completion of treatment, they may not have the immune response needed. So there is a time that I suggest they get the booster when they finish the therapy. My arbitrary timeline is around 4 to 6 months. Once they finish the chemotherapy, 4 to 6 months out, I ask them to get a booster dose or the vaccine.

October 2021

From the Editor-in-Chief: The Way Up

Building a Patient-Centered Cancer Center From the Ground Up

Addressing Disparities in Cancer Care and Beyond: What Can Be Done Now?

Dr David S. Hong: We Are Learning Every Day About Cellular Therapies

Conversations on CAR T: Study of Checkpoint Inhibitors After Transplant Bolsters Case for CAR T, Skarbnik Says

Conversations on CAR T: UAB’s Mehta Discusses Opportunities and Challenges

The Promise of Liquid Biopsies for Cancer Diagnosis

Specialty Therapies Offering Incremental Benefit Shouldn’t Be Added to Clinical Pathways, Hertler Says

Abstracts at ASCO Quality Show Uptake of Rapid NGS, Biomarker Testing Across OneOncology