Cancer care: The limits of immunotherapy
The Limits of Immunotherapy
Dr. Asher Chanan-Khan
Few people know cancer’s devastating effects more intimately than Dr. Asher Chanan-Khan.
The chairman of hematology and oncology at Mayo Clinic in Jacksonville, Chanan-Khan has focused his career on treating cancer patients with chronic lymphocytic leukemia and multiple myeloma, two diseases that remain incurable.
Chanan-Khan himself is a cancer survivor.
For all the advances over the past decade, however, Chanan- Khan is quick to acknowledge the risks and limitations of immunotherapy treatment, stimulating the body’s own immune system to recognize and destroy cancer cells.
“Almost 40% of the people die when we do immunotherapy treatment because we can’t control what the genetically boosted T-cells do once in the body,” he says.
Chanan-Khan says one of researchers’ biggest challenges today is determining whether immunotherapy constitutes a true benefit to the patient.
“I’m a cancer survivor myself, so I can say this: ‘When I am treated, I expect to be cured,’ “ he says. “But when immunotherapies are given to patients right now, they are not ‘cured.’ Some do very well for extended periods of time, and others don’t do well at all. What’s more, these are very expensive therapies.”
While immunotherapy is the most promising form of cancer treatment in the short term, Chanan-Khan says the ultimate answer to the disease lies elsewhere.
“I can imagine a time when I could give my son, who is now 8 years old, a multi-cancer vaccine,” he says. “And then I could say to my son, ‘You are now immune to all types of cancers that are common to men.’ That can only happen with vaccines. That’s not going to happen with medicine.”
“Cancer cells are like pirate ships. They lower their flag, and the immune system can’t recognize them. The big challenge now is how to get the immune system to go back, get past the tumor’s cloaking defenses and recognize and destroy the cancer cells.”
— Dr. Asher Chanan-Khan
Dr. Jose R. Conejo-Garcia, Co-leader
Moffitt Cancer Center’s Immunology Program
Q: What makes immunotherapy such a promising frontier in the fight against cancer?
A: Until recently, the problem we faced was finding the right formula of drugs to boost the immune system to target established tumors. Now, by boosting the immune system’s responses to tumors, we’re not only able to destroy tumors, but prevent occurrences.
Q: Which types of cancers respond best to immunotherapies?
A: The best responses we’ve seen are with melanomas and lung cancers, but the list is growing.
Q: What percentage of patients with those diseases respond well to immunotherapy?
A: Responses are limited to about a third of patients, and it is critically important to find out why some people respond so well to treatment, and why others don’t. That’s the ‘holy grail’ today in immunotherapy research.
Q: Does immunotherapy offer hope for early detection of cancers?
A: We’re conducting research here at Moffitt to detect microscopic breast cancer lesions. And we have trials going where we vaccinate so that patients don’t develop the full-blown disease. That’s another form of immunotherapy I believe will be very, very important.
Q: What makes immunotherapy more promising than chemotherapy?
A: Chemotherapy is a kind of carpet-bomb approach to treatment. With immunotherapy, the body’s immune system targets the entire body, including specific tumors we can’t detect with medical devices or tests.
Q: Is immunotherapy the future of cancer research?
A: Yes, immunotherapy is the future of our fight against cancer. This is a revolution, and we are seeing only the tip of the iceberg. I’m very, very optimistic about the future of immunotherapy treatments.
Moffitt Cancer Center: By the Numbers
» 5,200 – Employees
» $70,000 – Average salary
» $2.1 billion – Economic impact
» Patients from 67 Florida counties; 50 states and 133 countries
» 356,000 – Annual outpatient screenings; 56,000 unique patient screenings
» 11,708 – Patients placed on clinical trials over past five years
» 2,000 –Students trained in oncology annually
» $50 million – Peer-reviewed funding annually; $35 million non-peer reviewed
» 2.5 million – Square feet devoted to research and patient care
Source: Moffitt Cancer Center
U.S. News & World Report last year ranked Moffitt as the sixth-best cancer hospital in the nation; It has ranked consistently as one of the best hospitals for cancer care since 1999. Moffitt is the only National Cancer Institute-designated Comprehensive Cancer Center based in Florida.
Sylvester Comprehensive Cancer Center is investigating whether engineered human immune cells — called “Car-T cells” — can be used to fight lymphoma in patients for whom standard therapies have failed. T-cells are collected from the patients’ own blood and then engineered genetically so that “receptors” on the T-cells recognize a protein that’s present in the cancerous cells. The T-cells then begin to attack and kill the cancer. Phase two clinical trials, sponsored by Kite Pharma, are underway.
“While we have known for some time that T-cells from stem cell transplant donors can cure blood cancers that fail chemotherapy, the ability to induce remissions using genetically engineered T-cells from patients represents a true therapeutic breakthrough,” says Dr. Krishna V. Komanduri, director of Sylvester’s Adult Stem Cell Transplant Program.
Sylvester Comprehensive Cancer Center has partnered with the Caribbean Gynecologic Cancer Society and the University of the West Indies to create a fellowship that trains gynecologic oncologists in low- and middle-income countries in Latin America. The Caribbean Gynecologic Oncology Fellowship, a two-year program, will involve faculty from Sylvester and the University of Miami School of Medicine. Some of the curriculum will be conducted online. Participating physicians will have a thee-month observership at Sylvester and then do 21 months of clinical work in hospitals affiliated with UWI.
Early Detection: New Tests
Along with the advances in immunotherapy, researchers continue to attack cancer on another crucial front — early detection. Drs. Timmy Nguyen and Bruno Bastos, both oncologists at Cleveland Clinic’s Broward County headquarters, cite two screening tests, recently approved by the FDA, to detect early stages of colorectal cancer
“The stool DNA test is able to detect colorectal cancer in greater than 90% of individuals found through a colonoscopy exam to have colorectal cancer,” Bastos says.
The other recently FDA-approved screening test is a low radiation dose computed tomography (CT) scan of the chest.
This test has been shown to reduce patients’ risk of dying from lung cancer “by 20% when compared with patients screened with traditional chest X-rays,” Nguyen says.
An even newer screening test, with great potential to detect different types of cancer at early stages, is a liquid biopsy, not yet FDA-approved.
“This test can detect cancer cells and pieces of DNA from tumor cells in the blood or urine that shed from a growing solid tumor,” says Bastos.
“Currently, liquid biopsy has been found to be of great value in monitoring changes in a patient’s cancer over the course of their disease,” Nguyen says.
“We are at a point now where we have a subset of patients with lung, bladder, kidney and colon cancers that are benefiting from immunotherapy. I’d say between 10% to 50% of patients with all types of cancers are benefiting, and my prediction is those numbers will go up incrementally over the next five years.”
— Dr. Richard W. Joseph, Mayo Clinic Jacksonville
Sometimes, a Cure …
Dr. Tarek Eldawy, chairman of the Department of Medicine at Sacred Heart Hospital in Pensacola, says immunotherapy drugs unheard of five years ago are producing positive results in patients with cancers like melanoma or lung.
“I see some of my patients who were treated for melanoma seven or eight years ago with a drug called Yervoy,” says Eldawy. “When I look at my patients who have had this drug and haven’t had any reoccurrences of their cancer, in retrospect, yes, I think they are cured. That’s certainly qualifies as one definition of cure: No evidence of cancer after five years. To me that is amazing.”
… But Questions Remain
While some immunotherapy drugs, such as the widely advertised nivolumab, which treats advanced-stage lung cancers, melanoma and Hodgkin lymphoma, have extended the lives of patients, questions about the drugs’ overall effectiveness and their cost remain.
Clinical trials have shown that compared to a group of lung cancer patients who took only conventional chemotherapy, those taking the drug nivolumab lived an average of only 90 days longer.
Many patients reported severe side effects from the drug, whose brand name is Opdivo, a new drug that appears to be most effective in the treatment of non-small cell lung cancer tumors.
And there is the cost: About $150,000 for the initial treatment and then some $14,000 a month on average afterward. Not all insurance companies will cover the cost.
State Funding for Cancer Research
The Florida Legislature created the William B. “Bill” Bankhead Jr. and David Coley Cancer Research Program to advance progress toward cures for cancer through grants awarded through a peer-reviewed, competitive process.
Over the past three fiscal years, the program has awarded $26,429,260.
In 2016-17 the taxpayer-supported program provided research funds totaling more than $8.65 million to five grantees:
» University of Miami, $3,533,514
» Moffitt Cancer Center, $3,272,945
» University of Florida, $1,226,836
» Florida Atlantic University, $622,683
The Legislature also established the James and Esther King Biomedical Research Program to support research initiatives that include tobacco-related cancers.
Over the past three years, the program has awarded $9,904,509 for cancer-related research at five Florida health care and university-based research centers.
Source: Florida Department of Health
» $90,656 – Average patient cancer cost to health plans
» $4,000 – Average claim cost per ER visit for cancer pain
» 4 – Average number of ER visits per cancer patient
» 2 – Average number of in-patient admissions per cancer patient
» 51% – Percentage of cancer patients who receive chemotherapy within 14 to 30 days of passing away
» 6.4 – Average number of days a patient spends in hospice
» 65% – Proportion of cancer patients who spend their last days in the hospital; of those, 23% die in intensive care
Source: RN Cancer Guides
Tampa General Hospital’s liver transplant program, which has logged more than 1,400 liver transplants, is the only liver cancer program on the west coast of Florida offering transplants as a therapy for liver cancer.
Cancer’s Long History
The earliest written record regarding cancer is from around 1600 B.C., in Egyptian writings on papyrus that describe breast cancer. Hippocrates (circa 460 B.C.-370 B.C.) also described several kinds of cancer, referring to them with the Greek word karkinos which translates to “crab.” This name comes from the “crab-like” appearance of a cross-section of a solid malignant tumor whose veins branch out like legs on all sides.
The idea of fighting cancer by injecting malignant tumors with bacteria to stimulate the immune response is more than a century old, and there is evidence that it dates back some 2,000 years to the Greeks.
Nicklaus Children’s Hospital
Miami Children’s Health System, parent of Nicklaus Children’s Hospital, has 68 clinical trials and research programs related to pediatric oncology. They include:
» A vaccine-based immunotherapy for patients with recurrent Ewing’s Sarcoma. The hospital is one of six sites in the country participating in this study.
» Ketogenic diet — a high-fat, low-carbohydrate diet — to help manage pediatric patients receiving treatment for brain tumors
» Intra-ventricular chemotherapy for refractory brain tumors in children
» Stem cell transplant chemotherapy in children with brain tumors to avoid radiation
» Nicklaus also is conducting research on a minimally invasive laser procedure called Visualase for removing brain tumors in children. Nicklaus was the first hospital in the Southeast, and second in the nation, to offer MRI-guided laser ablation for tumor removal in some epilepsy patients.
» 18.1 million – Cancer survivors in 2020, 30% more than in 2010
» $157 billion – Costs of cancer care in 2010 dollars, expected to reach $207 billion by 2020
» Growth and aging of the U.S. population is the primary cause of increases.
Source: National Cancer Institute
Send in the Bio-Marines
Not all cancer-related research takes place in medical center surroundings. Researchers at Harbor Branch Oceanographic Institute investigate compounds found naturally in the marine environment that may help fight cancer — not necessarily by killing the cancer cells outright, but by inhibiting the progression of the disease.
A major focus is pancreatic cancer. Cancer cells usually grow quickly, and much of the Harbor Branch research focuses on marine substances that inhibit that fast growth in some fashion — by reducing pancreatic cancer cells’ resistance to the normal process of cell death, for example, or by blocking the process by which cancer cells get their nutrients. Harbor Branch’s cancer-related research is directed by associate research professor Esther Guzmán.
M.D. Anderson Partnership
A nine-story, 330,000-sq.-ft., $130-million building is under construction on the campus of Baptist Health System in Jacksonville to house the M.D. Anderson Cancer Center. In 2015, Baptist and Anderson established a partnership in which Baptist personnel are trained in and replicate the M.D. Anderson protocols for treating cancer. The building is expected to open in 2018.
“I continue to believe the role of federal government is to prime the engine of medical discovery. And the goal of the (Beau Biden Cancer) Moonshot is to give the research that comes out of the universities enough momentum so that the discoveries can be quickly picked up by the private capital necessary to put these medical and drug breakthroughs over the finish line.”
— Greg Simon, former director of the $1.8-billion Moonshot initiative
Open for Business
Baptist Health South Florida has opened its $430-million, 445,000-sq.-ft. Miami Cancer Institute. The institute is the only Florida institution that’s part of the Memorial Sloan Kettering Cancer Alliance, an effort to ensure that patients have access to the most effective treatment. The Miami Cancer Institute also houses south Florida’s first proton therapy center, one of fewer than two dozen proton therapy centers in the nation. Proton therapy enables radiation oncologists to target tumors with precisely aimed radiation that doesn’t damage healthy cells near the tumor. UF Shands also operates a proton therapy center in Jacksonville.
Creating a Healing Environment
Miami Cancer Institute is among the institutions seeking to make chemotherapy less intimidating for patients. The institute’s treatment area, for example, offers a room with augmented reality for children. An interactive screen lets the child choose a setting like a beach, marine environment, space or some other place and “transport” themselves there virtually as a diversion while receiving chemotherapy. Steve Holan, vice president of clinical operations, says a staff person can ask the children, “Where do you guys want to heal today?”
Lynn Rasys has been named executive director of the Florida Cancer Specialists Foundation, a nonprofit organization that provides financial help for non-medical living expenses to qualified cancer patients. She previously directed the foundation’s volunteer program and was executive director of the Susan G. Komen for the Cure, Florida Suncoast chapter. The foundation was established in 2011 by physicians at Florida Cancer Specialists, a group of for-profit oncology and hematology practices — the largest such group in the country, it says — with nearly 100 locations in the state. The company and the foundation are based in Fort Myers.
Difference of Opinion
A University of Florida advisory council recommends that men in Florida 50 and older with average risk profiles should get early prostate cancer detection tests. All African- American men and everyone 40 and older with a history of prostate cancer in their families should get tests, the council recommends. The council came into being in 2011 after the state Legislature directed UF’s Prostate Disease Center to establish an advisory group to development ways to improve outreach and education.
The UF panel’s recommendations, however, differ somewhat from federal guidelines that recommend against routine use of the PSA test to screen for prostate cancer. The tests aren’t always reliable and can lead to unnecessary treatment.
Dr. Thomas Stringer, executive director of the council and the UF Prostate Disease Center, says his group’s recommendations reflect “unique Florida subpopulations at increased prostate cancer diagnosis, including older and African-American men.” Both of those populations are present in Florida at higherthan- national averages. “Early diagnosis remains key to longterm cancer survivorship.”
The total cost of all cancer hospitalizations in Florida during 2013, the latest figure available, topped $5.67 billion.
Source: Agency for Health Care Administration
Young Adult Patients
Pediatric oncologist Peter Shaw, deputy director of the Johns Hopkins All Children’s Cancer & Blood Disorders Institute in St. Petersburg, wants to enable more young adults to be treated in a children’s hospital setting. At an adult hospital, adolescents and young adults are often the youngest patients. At Johns Hopkins All Children’s, oncology patients must be 21 or younger, a limit imposed in part by state requirements. Shaw, an expert in clinical trials and standards of care for adolescents and young adults, would like to see that age raised to 25. Johns Hopkins All Children’s and nearby Moffitt Cancer Center share an adolescent and young adult oncology program focused on patients with cancers of the bone, muscle and connective tissue and may expand their cooperation to other cancers involving young adults.