Advances in Cancer Care Demand Access for All, City of Hope Leaders Say

The scientific advances of the past generation in cancer care are not reaching everyone. Truly “patient-centered” care requires giving equal access to the best treatments, said Joseph Alvarnas, MD, to kick off “Closing the Access Gap—Ensuring Innovation Saves Lives,” an installment of the Institute for Value-Based Medicine® series presented by The American Journal of Managed Care® in partnership with City of Hope.

The event, held in Irvine, California, on September 15, convened as Alvarnas and his City of Hope colleagues waited to hear whether Governor Gavin Newsom would sign the Cancer Care Equity Act, which the National Cancer Institute–designed center has supported to close gaps in cancer outcomes between patients with commercial insurance and those covered by Medi-Cal, the state’s Medicaid program.¹ Alvarnas, vice president for government affairs and chief clinical advisor, AccessHope, thanked those who had advocated for the legislation, which Newsom later signed on September 28. The law, set to take effect on January 1, 2023, gives Medi-Cal patients with complex cancer case access to specialized cancer care.²

“The things that we can do alone are amazing, [and] the things that we can do together are truly extraordinary,” said Alvarnas, who serves as City of Hope’s vice president for government affairs and chief clinical advisor of AccessHope. He said the law will let community oncologists and academic centers collaborate on complex cancer cases.

The legislation follows the creation of AccessHope, an employer-driven initiative that offers a remote “second opinion” on challenging or rare cancer cases without requiring the patient to travel long distances or leave the care of the local oncologist.

Collaborating to Benefit Patients
The first panel discussion, centering on partnerships between academic centers and community oncologists, featured Mary Cianfrocca, DO, MBA, City of Hope’s senior medical director of community practices, and Afsaneh Barzi, MD, PhD, director of AccessHope.

Cianfrocca said that community oncologists see every type of case that comes through the door, from the most basic to the highly complex. “That’s the result of all these new targeted drugs that have been really beneficial to patients,” she said. “But [all the new therapies represent] a tremendous amount of knowledge that the average community oncologist needs to absorb, process, and then apply to an individual patient.”

Relationships with academic centers and Compre­hensive Cancer Centers can help physicians in community oncology practices process that information and ensure that patients gain access to the best possible treatments, Cianfrocca said, “and that the patient is getting care at the right time, the right place.

“We can do a lot more together than we can do apart,” she said.
Barzi said AccessHope represents an innovation in care delivery, in that it’s driven by self-insured employers. Sometimes, she said, the local oncologist doesn’t know what they don’t know. AccessHope can review the case and connect with the treating oncologist, “with the hope of elevating treatment to where it should be,” Barzi said.

The case review “is not based on the request of [the community] oncologist—it’s for all comers,” she said. “That’s where you realize where the gaps are.”
One particular issue has arisen with the advent of next-generation sequencing; the technology is still relatively new and sometimes isn’t used to its full advantage, Barzi said. She walked through an example involving a patient with gastrointestinal cancer—which is her area of expertise—in which she collaborated with a local oncologist and pointed out that the tissue sample used was not sufficient to test for a KRAS mutation, which is among the most common mutations.

Alvarnas said these kinds of collaborations can save lives and often reduce low-value care. The problem is that the reimbursement system does not always reward community oncologists and academic centers for working together while keeping patients close to home. Instead of looking at care as making a choice between academic and community oncology, he said, “Why not look at ways to bridge the gap, bring them together, make them [a single] unit?”

How Precision Medicine Is Transforming Oncology, Saving Lives
Ed Kim, MD, MBA, senior vice president and physician-in-chief for City of Hope Orange County, led a discussion on advances in precision medicine with 2 City of Hope directors: Amrita Krishnan, MD, of the Judy and Bernard Briskin Center for Multiple Myeloma Research, and Cristian Tomasetti, PhD, a mathematician from the Center for Cancer Prevention and Early Detection.

Kim asked both Krishnan and Tomasetti for an overview of changes in their respective fields. In multiple myeloma (MM), Krishnan said, median survival has more than doubled in the last decade, thanks to better understanding of disease biology and a bounty of new treatments, including immunotherapy and targeted therapy. “[Advances] have moved the treatment of myeloma beyond our imagination,” she said, “to the point where I think we can use the 4-letter word: cure.”

Lung cancer isn’t as far along, Kim said, but there are many more targeted therapies and biomarkers to assess than there used to be. Tomasetti weighed in with examples from colorectal disease, in which the use of liquid biopsy is allowing clinicians to spot cancer signals after surgery, and artificial intelligence, which he said is dramatically changing early detection techniques.

Kim then asked for comments on the use of testing for minimal residual disease (MRD), which Krishnan said has been fairly well established as a tool in decision-making, vs monoclonal gammopathy of undetermined significance (MGUS), which is a condition of abnormal protein in the blood that can be a precursor to MM. The use of MGUS is less clear.

The question today with MRD, Krishnan said, is how to use this marker to decide when therapy can stop—an issue of enormous importance to both payers and patients. “Clearly, MRD is going to guide our future in terms of therapeutic decision-making,” she said.

Kim asked Tomasetti how to translate all the data from MRD testing. Right now, Tomasetti said, “You check the blood every 3 months, but [this] depends on the cancer type and on the specific study. I think in the future [this will] become more and more sensitive.” Monitoring will evolve to be able to track disease on the subclonal level, and therapy will follow.

Krishnan followed up on the MGUS issue, saying that understanding what to do with these patients, beyond monitoring them, is difficult. “MGUS and smoldering myeloma are probably the most controversial things we have in the field now,” she said. Stratification models are “pretty crude.” She mentioned a study presented in December 2021 from Iceland that found MGUS in 15% of the population.³ “Now the problem is, what do you do with that? Because who do you treat?

“Understanding the biology is equally important for us,” she said.
Tomasetti said that a key question moving forward will be going beyond the germline mutation and capturing “the somatic component,” to properly stratify risk. Air pollution, for example, can cause a higher incidence of lung cancer in those who have EGFR or KRAS in their normal tissue. Kim posited what it would take to design a trial to study the 15% of people with MGUS who face increased multiple myeloma risk, based on the Iceland study.

”The first thing you need to do,” said Krishnan in response, “is pick a very young [principal investigator].” The room broke out in laughter.
Tomasetti advised, “I think the goal should be more humble.” It doesn’t take 20 years to show changes, and technology will allow a more complete picture that will make stratification easier.

Kim referred to how long it took to win support for lung cancer screening, and the many thousands of patients involved. The problem with using MGUS or another marker, he said, is that “you have to be seeing a primary care physician regularly and have it detected. And there are a lot of access issues in this country.”

Searching for Health Equity, Better Outcomes
Loretta Erhunmwunsee, MD, has 2 roles at City of Hope: She is an assistant professor in the Department of Surgery, and she also has an appointment in the Division of Health Equities, Department of Population Sciences. She opened her talk on equitable care and closing gaps in access with this in mind: “I am a health equity researcher who’s passionate about this. So that means I can talk about this for forever,” she said. “And I’m also a thoracic surgeon. So, I believe in efficiency.”

Erhunmwunsee distinguished between disparities, which she characterized as the differences in incidence and prevalence of disease and health conditions among population groups, and health equity, which she said, “is a bit different. It’s the concerns that those differences in the population health...can be traced to unequal economic and social conditions that are systemic and avoidable—and therefore, inherently unjust, and unfair.”

In some cases, she said, disparities are the result of specific laws or policies designed to leave some groups behind, such as zoning that left some groups with inferior housing or closer to highways, where they would be affected by pollution.

As a surgeon, Erhunmwunsee sees the effects of health disparities in patients with lung cancer. “These are the patients who I treat and who I know,” she said. Overall, in the United States, the average age-adjusted incidence of lung cancer is 60.4 per 100,000 people, but among the Black population it ranges from 64.1 to 115 per 100,000 people, with the highest incidence in parts of the South.

Getting the country to a state of health equity—and closing these disparities—will not happen without understanding the social determinants of health (SDOH) that drive these numbers, she said. Even if the patient is at a place like City of Hope, the care team must understand a patient’s situation: Does the patient have housing? Adequate food? What are their stressors?

That includes having access to care and health coverage.

“When we think about health equity, and achieving equity in care, we need to understand that health care access is one part. But there are several [other] different parts as well,” she said. “And these SDOH are shaped by the distribution of money, power, and resources across society. They impact how well a person lives and how long they live. As you know, many people have different sorts of definitions of SDOH, but they usually are…economic stability, neighborhood and physical environment, education, health access social context. And it’s important to understand that a person’s overall health is dependent on these.

“When you have inequities in pollution or deprived neighborhoods, or in unequal employment opportunities and low-quality schools, food deserts and underfunded health care systems, you will continue to bake in inequities that will lead to already marginalized people having worse outcomes,” Erhunmwunsee said.

In recent years, disparities in cancer outcomes—including mortality—have been well documented in reports by the American Association for Cancer Research. But the blueprint on what to do remains a challenge, because all the upstream factors must be addressed. Problems like neighborhood exposures and pollution can lead to somatic and epigenetic alterations.
“Poverty and deprivation levels are linked to aggressive carcinomas,” Erhunmwunsee said. While access to health care is a major reason for poor outcomes, she explained, more research is showing how the stress of poverty itself contributes to aggressive cancer. Her own research has now documented the connection between neighborhood pollution and the presence of TP53-mutated non–small cell lung cancer,⁴ and upcoming work will document the connection between neighborhood disadvantage indexes and KRAS mutations.

Looking ahead, Erhunmwunsee wants to vastly increase lung screening among eligible Californians who have not being screened. City of Hope is working with Federally Qualified Health Centers to improve the screening rate, especially among minority groups. In addition, “the primary care physicians who took care of these patients very often didn’t fully understand the benefit of lung cancer screening,” she said, indicating that better education of these physicians is necessary.

Moonshot 2.0 Moves Toward Equity
Steven Rosen, MD, provost and chief scientific officer for City of Hope, and Eileen Smith, MD, chair of the Department of Hematology & Hematopoietic Cell Transplantation, kept the equity discussion going with a look at Cancer Moonshot, which President Joe Biden relaunched as version 2.0 in 2022 after its initial run during his final year as vice president in the Obama administration.

Smith outlined the goals of the original Cancer Moonshot in 2016: accelerate progress in curing cancer, increase collaboration among researchers, and improve data sharing. “If [we ask], ‘Was the Moonshot successful?’ clearly everything wasn’t solved, or we wouldn’t have Moonshot 2.0,” she said. “But I have to say, I think it was a terrific success in terms of what it did accomplish.”

All 3 goals were met, Smith said: The first Moonshot led to 70 research consortiums, 240 research projects, and “significant progress made in fields where investment was necessary to increase translation of science, from the bench to the applicability to patients.” She pointed to advances in immunotherapy, rare cancers, and pediatric cancers, and the development of a biorepository with tissue for research.

“The most extraordinary thing about the Moonshot was that it really accelerated the development of cancer informatics” through the Cancer Data Commons, Smith said. As of 2020, this resource had been used by 70,000 researchers with 70 million hours of analytics. The open access policies of the initiative mean that journal editors who publish studies using data gleaned from the Data Commons must agree to make the data available.

But the Cancer Moonshot had a missing piece. “It’s not just about science, and about the progress,” said Smith. “It’s about disseminating that [progress] fairly and equitably…The progress [engendered by] the Cancer Moonshot didn’t help everybody. And if you look at age-related cancer deaths across the country, what you see are wide disparities, and in parts of this country, cancer deaths are, incredibly, [much] higher [than in others]. And no surprise, those are areas in which people are living in rural areas in poverty, [and] in places where systemic racism prevents individuals from getting access to care.”

The difference in Moonshot 2.0, Smith said, is that the key objectives include addressing health inequities. “If we don’t deal with health and health inequities, we really are not going to solve the problem of cancer,” she said. “Another [objective] is to support patients, caregivers, and survivors. This is increasingly important now that more patients are cancer survivors.”

Forman Reviews 40 Years of Progress in Blood Cancers
Stephen J. Forman, MD, who preceded Smith as department chair, has spent 40 years at City of Hope and remains director of the Hematologic Malignancies Research Institute and director of the T-cell Therapeutics Laboratories. Forman, one of the world’s experts in leukemia, lymphoma, and bone marrow transplants, concluded the evening with a review of the extraordinary progress in treating blood cancers—which has made the once-unthinkable word “cure” possible in many cases.

Forman reviewed progress across multiple disease states, including chronic myelogenous leukemia (CML), acute myeloid leukemia (AML), MM, and chronic lymphocytic leukemia (CLL). He also discussed the trajectory of the use of hematopoietic cell transplantation: Once reserved mostly for younger patients, it is now an option for older ones as well.

When Forman was training as a physician, the only treatment for CML was controlling the high white blood counts; nearly all patients eventually developed acute leukemia and died within 5 years. Bone marrow transplants were a big step; about 80% of patients were cured and could lead a normal life. During this time, the Philadelphia chromosome was identified, which led to clinical trials for an inhibitor (imatinib). “The response rate was nearly 100%,” Forman said. “And of the people who responded, many went into complete remission.”

Transplants are still needed for patients who become resistant to imatinib or to second- or third-generation medications. More recently, researchers have studied patients who took the drug for 5 years, achieved complete molecular remission for the last 3 to 4 years of that span, then stopped taking it. “A large number of patients now have come off the drug, and the disease has not come back,” he said. “It just represents a remarkable achievement—from a fatal disease becoming a curable disease over a period of 30 to 40 years.”

He turned to AML, calling it “a disease that scares everybody.” AML is now understood to be an umbrella term for many diseases, including a type called acute promyelocytic leukemia (APL), now considered more curable. A challenge with AML is that it’s more common among the elderly, who often could not tolerate intensive chemotherapy. “But in the last 5 years, there’s been a new approach to AML, utilizing 2 new classes of drugs that just didn’t even exist 10, 15, 20 years ago,” said Forman. “We’re using that now in older people, and getting responses and some remissions, and some are living several years.”

Transplant evolution. Forman explained that autologous transplants are used primarily for MM, lymphoma, and Hodgkin disease, while allogenic transplants are used in acute leukemia and for patients who have marrow involvement with hematologic cancers, including myelodysplastic syndrome. Years ago, allogenic transplants were rarely attempted in patients older than 30 years, but today, even patients older than 70 years receive them. A registry of volunteer donors now numbers above 20 million. Early on, siblings offered the best hope of a match, but over time researchers figured out how to do “half-match” transplants.

“So now we can find a donor for nearly all patients who need to have a transplant,” said Forman. “This was particularly important to us at City of Hope, because there was a large, underserved population of people for whom we were having trouble finding donors. If we had a patient whose parents were of different ethnicities, we had trouble finding a match.”

More therapeutic advances. Forman reviewed the advances in CLL over the past 15 years, from single-agent chlorambucil; to combinations with fludarabine, cyclophosphamide, and rituximab; to Bruton tyrosine kinase inhibitors, new B-cell antibodies, and the BCL2 inhibitors. As with CML, CLL has gone from an incurable disease to one that can be controlled and possibly cured.

Advances in MM abound—including upfront options such as lenalidomide, bortezomib, and carfilzomib. “You could see, steadily, that those disease control and survival rates were going up with each step,” he said, adding that patients can live for a very long time.

“The first chemotherapy was given in the 1940s to children with acute leukemia in Boston by a man named Sidney Farber,” at what is now Dana-Farber Cancer Institute. The first few children went into remission after being treated with what is now called methotrexate. Decades later came targeted therapies such as imatinib, and later immunotherapy—which, Forman noted, saved the life of former President Jimmy Carter, who had melanoma in the brain.

The progress in lung cancer “has just been breathtaking,” he said. “My lung cancer colleagues are so excited, in a way that I’ve not seen in 15 to 20 years, because they can do so much about the subtypes of lung cancer.”

Forman told the story of chimeric antigen receptor (CAR) T-cell therapy and Emily Whitehead, a 6-year-old child headed for hospice when she was given the first treatment for acute lymphoblastic leukemia. Twenty-eight days later, “they could not find a leukemia cell in her blood,” he said, showing a series of photos of Emily as she grew up.

Not just children and young adults are seeing these results, he said. In City of Hope’s trials with CAR T-cell therapy in patients older than 50 years, the response rate was 100%.

Every year, City of Hope hosts a survivor reunion for patients on Mother’s Day weekend. While sharing a photo from a reunion, Forman concluded, “There are pictures in my head of the people who, had we known then what we know now, would be in this picture and a lot of other family pictures. And that is the reason we get up to go to work every day.” 

References
1. Cancer Care Equity Act – SB987 (Portantino). American Cancer Society Cancer Action Network. Accessed September 28, 2022. https://www.fightcancer.org/california-cancer-care-equity-act-sb987-portantino
2. Marquez L. Gov. Newsom signs landmark cancer access legislation
into law, California Cancer Coalition celebrates. News release.
City of Hope; September 28, 2022. Accessed September 28, 2022.
https://bit.ly/3rgLVBq
3. Screening for monoclonal gammopathy of undetermined significance: a population-based randomized clinical trial. first results from the Iceland Screens, Treats, or Prevents Multiple Myeloma (iStopMM) study. Presented at: 63rd American Society of Hematology Meeting & Exposition; December 11-14, 2021; Atlanta, GA. Abstract 156. https://ash.confex.com/ash/2021/webprogram/Paper152333.html
4. Erhunmwunsee L, Wing SE, Shen J, et al. The association between polluted neighborhoods and TP53-mutated non–small cell lung cancer. Cancer Epidemiol Biomarker Preven. 2021;30(8):1498-1505. doi:10.1158/1055-9965.EPI-20-1555