By Kasey Fuqua
Though immunotherapy is one of the fastest growing areas of cancer treatment, this area of cancer treatment got its start in 1893 when physician William Coley first used bacteria to treat sarcomas. After more than a century of research, new immunotherapy drugs are now gaining FDA approval on almost a monthly basis.
“This is an exciting time because we see approvals left and right,” says Dr. Aisha Zaidi, medical oncologist with Riverside Medical Group. “It’s amazing how many immunotherapy drugs in combination with chemotherapy drugs are out there in the pipeline.”
The modern breakthroughs in immunotherapy began in 2001 when researchers identified the PDL1 immune checkpoint pathway that made many of today’s treatments possible. By 2011, a new treatment for metastatic melanoma extended patient survival time significantly, marking a huge breakthrough in immunotherapy.
“No cancer patient should give up before a dose of immunotherapy,” says Ligeng Tian, MD, PhD, medical oncologist at Virginia Oncology Associates. “We really see miracles in what immunotherapy has done for people.”
Physicians and researchers are achieving breakthroughs in every type of immunotherapy treatment, including:
Checkpoint Inhibitors
Checkpoint inhibitors are showing huge promise for cancers that previously had few effective treatment options, including patients with stage 3 lung cancer and stage 4 melanoma.
In 2017, more patients than ever gained access to checkpoint inhibitors. The FDA approved pembrolizumab to treat any type of solid tumor—from colon cancer to kidney cancer—in adults and children, as long as the cancer cells are deficient in mismatch repair (MMR) or have high microsatellite instability. These cancer cells tend to have a higher number of DNA mutations, meaning they have more abnormal antigens.
This is the first type of cancer treatment to be approved based on the cancer’s molecular features instead of its specific site of development. It gives patients with many different types of cancer a new treatment option and new hope.
“In the clinical trial, they included patients with cancers of many types, and patients showed an excellent response rate,” says Dr. Tian. “It doesn’t matter any more what type of cancer you have or what treatments you do or do not quality for; as long as you have these characteristics demonstrated in cancer tissues, you can use this drug and you may have a chance. This is revolutionary.”
Both Dr. Zaidi and Dr. Tian encourage patients and physicians to look at the response rate of immunotherapy drugs before pinning their hopes on these new therapies. While checkpoint inhibitors can be incredibly effective, they may only work in a small group of patients.
“A lot of people think these are miracle drugs, and they are, but only in those where they work,” says Dr. Zaidi. “In patients with metastatic melanoma, there’s roughly a 20 percent response rate, but those people are alive beyond 10 years, which is remarkable and unheard of just a few years ago.”
Unfortunately, checkpoint inhibitors have not shown as much promise in pediatric patients as adults.
“There are a number of theories on why checkpoint inhibitors aren’t as effective,” says Eric Lowe, MD, pediatric oncologist at Children’s Hospital of The King’s Daughters. “Some of it has to do with the genetics of cancer and the different types of cancer in children. We are definitely trying them in clinical trials, but they haven’t shown as much potential as in adult diseases.”
Chimeric Antigen Receptor (CAR) T-Cell Therapy
Though checkpoint inhibitors are not as effective in children currently, chimeric antigen receptor (CAR) T-cell therapy has been a much larger success in children with lymphoma and leukemia.
Because of the complicated equipment and expertise required to manufacture the CAR T-cells, the therapy is only available in around 10 to 20 locations around the country. Patients from Hampton Roads needing these therapies must travel to The National Institute of Health in Maryland or to Duke Medical Center in North Carolina.
“T cell therapy has worked wonders in some diseases in kids, specifically in acute lymphoblastic leukemia,” says Dr. Lowe. “We have sent patients to receive CAR T-cell therapy and seen benefits for these kids.”
Monoclonal Antibodies
One of the oldest forms of immunotherapy, monoclonal antibodies still play a huge role in cancer treatment today. At CHKD, Dr. Lowe and his fellow oncologists enroll patients in clinical trials for bispecific monoclonal antibodies.
“The idea of these treatments is to get T-cells in proximity to the cancer cell, then activate them to attack the cancer,” says Dr. Lowe.
Other studies are examining how monoclonal antibodies work in combination with other immunotherapy agents, chemotherapy or radiation therapy. These drugs remain one of the most common immunotherapy treatments available.
The Future of Immunotherapy and Medical Oncology
In many ways, today’s treatments reflect the future of cancer care. While immunotherapy will play a large role, treatments like chemotherapy or radiation therapy won’t be going away.
“Don’t disregard traditional chemotherapy,” says Dr. Zaidi. “We have seen in patients that have undergone radiation therapy and chemotherapy, when we monitor their T-cell response, that response went up. When we gave immunotherapy to those patients, they did much better.”
Dr. Tian also believes new agents may target different immune cell molecules. Though trials targeting these molecules are currently ongoing, none are close to market yet and some may never make it to patient’s bedsides.
“Because immunotherapy is so promising and toxicity is so tolerable and is becoming so effective, new immunotherapy drugs are really what everybody is looking for,” says Dr. Tian. “Still, a crucial part of cancer treatment is and will continue to be targeted therapy.”
The biggest difference between current and future treatments may be an increase in the number of targeted therapies available. Physicians and scientists are constantly learning more about the molecular make-up of cancer tumors. Dr. Zaidi believes this understanding of the microenvironment and genetic make-up of cancer tumors will be the future of treatment, helping identify why some patients respond to treatment and others don’t.
“When we talk about personalized medicine or targeted therapy, we should be able to map that pathway that’s causing people to be resistant to immunotherapy,” says Dr. Zaidi. “I think that’s really where the cure is going to be, if we are able to identify those roadblocks to effective treatment.”
Dr. Lowe agrees that the ability to understand the genetics and molecular drivers of cancer is the key to the future of cancer treatment.
“If we can really get down to what is driving the cancer in the first place, I think we are going to get better at treating cancer and curing it,” says Dr. Lowe. “If we can’t cure it, we should be able to make it like a chronic disease where we can use medicines that keep you alive until you are 70 or older.”
Dr. Tian also predicts that patients will spend less time in cancer centers. Already immunotherapy has shorter infusion times than chemotherapy. She also believes medical oncology treatments will consist of more injections and pills instead of IV infusions, a benefit of targeted therapy some of her lung cancer patients already enjoy today.
“I have patients coming in for targeted therapy who have never had a port put in,” says Dr. Tian. “They have never sat in the infusion room. They just come in for a check.”
The ultimate goal in immunotherapy treatment in Dr. Lowe’s mind would be a vaccine that prevents cancer development or recurrence.
“The very distant future of cancer treatment is hopefully vaccines so cancer doesn’t occur in the first place,” says Dr. Lowe. “Will that happen in my lifetime? Probably for a disease or two, but not for all cancers.”
Whether as a pill, infusion or vaccine, immunotherapy is quickly expanding the range of treatment options for cancer patients. As new treatments continue to gain approval throughout 2018 and beyond, patients are more likely to experience longer survival times, and in some cases, a cure for their cancer.
