HEALTH NEWS

My Two-Decade Journey with Cancer Immunotherapy

Written by Jamie Reno on January 23, 2018

This writer was once told his cancer had nothing to do with his immune system. The medical view on immunotherapy has changed dramatically since then.

Jamie Reno

Jamie Reno, 21-year survivor of lymphoma

When I received a diagnosis of stage 4 non-Hodgkin’s lymphoma two decades ago, I asked my oncologist what I could do to boost my body’s immune system to fight the cancer.

He gave me a condescending look over his glasses and said, “Mr. Reno, your cancer has nothing to do with your immune system.”

I was shocked. “Respectfully, doctor, that makes no sense,” I said.

He grunted. But I let it go. I was dealing with a cancer diagnosis and didn’t have the will at that moment to challenge him.

I soon learned that while not every oncologist shared his dismissive opinion of immunotherapy — the science of harnessing the body’s immune system to fight disease — many surprisingly did.

My doctor recommended a type of chemotherapy called . It was rough. I got quite sick. But it gave me 2 1/2 years of remission.

When the cancer recurred, I’d evolved from a scared cancer newbie to an informed and determined cancer veteran.

After mulling my options and getting a new and better doctor, I took an educated risk and enrolled in an experimental clinical trial of a radioimmunotherapy (RIT) called That treatment involved a monoclonal antibody linked to a radioactive molecule.

Bexxar, a safe and effective treatment that saved many lymphoma patients’ lives, gave me a complete remission that lasted more than 12 years — four times longer than the chemo had given me.

But the drug was by its manufacturer GSK in 2014 because it wasn’t bringing the company enough money.

There’s still RIT available for people with lymphoma called Zevalin, but that drug is now at risk of as well.

Times are changing

Ever since my clinical trial, I’ve been on a quest to learn more about how our immune system can fight cancer.

Some describe this quest as quixotic. Others say it’s obsessive.

Regardless, the good news is that much has changed in the cancer universe since I first received my diagnosis 21 years ago. And even since Bexxar was shelved in 2014.

Today, a patient would be hard-pressed to find an oncologist who still believes the immune system has “nothing to do” with cancer.

All but the most uninformed or stubborn doctors now recognize that the body has an immune system that fights cancer, and that there’s vast potential in developing drugs that harness it.

While cancer patients have relied on surgery, chemotherapy, and radiotherapy seemingly forever, immunotherapy has come of age.

It’s now one of the leading wings of cancer drug development, and easily the most written about in the past few years.

Among the biggest milestones for immunotherapy was the U.S. Food and Drug Administration’s (FDA) approval in 2014 of Keytruda, an immunotherapy from Merck for advanced melanoma.

Keytruda works by blocking PD-1, a protein on some cells that works like a stop sign to inactivate the body’s T cells. Those T cells help the body fight cancer and other diseases.

Just three months after Keytruda was approved, the FDA approved , a similar drug for advanced melanoma from Bristol-Myers Squibb that also inhibits PD-1 on cancer cells.

Keytruda and Opdivo have both since been approved to treat several other cancers.

And like many immunotherapies, they’re often used in tandem with other treatments, including targeted therapies, to improve patients’ outcomes.

Immunotherapy world’s rock star

The real rock star in immunotherapy is CAR T-cell therapy.

CAR (chimeric antigen receptor) T-cell therapy, a type of gene therapy, engineers the T cells from a patient’s blood, then reinjects them in the patient to seek and destroy cancer.

For many patients, it works more effectively against their cancer than anything else we’ve seen.

Because of its unprecedented percentage of complete remissions in cancer patients who have exhausted all other options, CAR T has enjoyed .

In the past five months, the FDA has approved two CAR T-cell therapies.

Kymriah, a treatment for a type of childhood leukemia from Novartis, made history in August when it became the first gene therapy available in the United States.

Two months later, Yescarta, a treatment for non-Hodgkin’s lymphoma from Gilead Sciences, .

Kymriah has also just been given the “” process by the FDA for treatment of lymphoma.

Several other CAR T-cell therapies are expected to be approved soon, including is0-cel (formerly ) for people with aggressive B-cell non-Hodgkin’s lymphoma, from Juno Therapeutics and Celgene.

The clinical trial data for is0-cel shows high response rates and a relatively low rate of side effects, according to an at the American Society of Hematology convention in Atlanta last month.

It was also Monday that Juno is being purchased by the larger Celgene in a $9 billion deal. 

There are reportedly some 200 trials currently under way for various CAR T treatments and combinations with CAR T and other drugs.

Though not everyone responds to CAR T, some physicians and researchers consider it to be a possible cure for certain cancers, as efforts continue to perfect it.

Is CAR T too expensive?

There’s been some fervent pushback from patients and patient advocates over the price of CAR T drugs.

Gilead charges $373,000 for Yescarta. Novartis charges $475,000 for Kymriah, but the company says it’ll offer refunds if the treatment doesn’t work.

Novartis, which reportedly spent $1 billion to bring Kymriah to market, has also created Kymriah Cares to help patients pay for the drug.

In addition, the company has pledged to offer an access program for eligible uninsured and underinsured patients.

Last month, the nonprofit Institute for Clinical and Economic Review (ICER) of CAR T therapies compared to chemotherapy.

It took into consideration patient survival, quality of life, and healthcare costs over the lifetime of the patient.

The institute selected researchers from the University of Colorado’s Skaggs School of Pharmacy and Pharmaceutical Sciences.

The researchers found that CAR T significantly extended the lives of some patients to a much greater degree than traditional chemotherapy. They concluded CAR T is cost-effective.

They also stated the clinical benefit may justify the expensive price.

CAR T is a one-shot deal

The price issue is certainly fair to raise, but it’s largely a misnomer.

CAR T is a one-shot deal, literally. It’s an infusion, a one-time treatment.

Many cancer therapies consist of multiple treatments taken over extended periods of time.

Chemo can last six months to several years, with treatment every two, three, or four weeks.

In the case of many newer cancer drugs like ibrutinib, which Dr.China covered in a story on a Sept. 11 rescue and recovery worker, the treatments are ongoing and can last years.

Same goes with , the most popular lymphoma drug in the world. Often, Rituxan is administered as part of what is called maintenance therapy. This can be astronomically expensive.

In comparison, a one-time CAR T-cell therapy, while certainly expensive on its face, is considered by many to be a bargain — something insurance companies certainly consider.

Immunotherapy and personalized medicine

Keytruda, Opdivo, and CAR T are just the tip of the iceberg.

Immunotherapy is branching off in new and fascinating directions. It’s now the engine that drives personalized medicine, arguably the hottest trend in healthcare.

Personalized medicine, or precision medicine, simply means the tailoring of a treatment to the individual patient based on their chemistry, genetics, and predicted response or risk of disease.

But what is still not widely known is the real science behind immunotherapy.

Namely, the fact that it’s enabled and profoundly enhanced by state-of-the-art diagnostic approaches that provide a deeper understanding of the molecular basis of disease than we’ve ever seen.

This includes developing important tests using the patient’s tumor, tissue, and blood.

These tests enhance the effectiveness of immunotherapies and increase the certainty that they’re safe and are what’s best for the individual patient.

Cancer Genetics Inc. (CGI) is one of the companies that does these essential tests.

CGI, with offices in the United States, China, and India, partners with some of the world’s largest pharma to better understand the needs and predispositions of each patient.

CGI’s proprietary testing tell physicians more than they’ve previously known about the patient’s cancer and how it’ll respond to treatment.

Some immunotherapies, specifically CAR T, have been halted because of side effects, including something called cytokine release syndrome, which can be fatal.

CGI’s genetic information tells the doctor if the patient is getting the immune system response that’s expected and whether other immune behaviors are occurring, including cytokine release.

“We are living in a renaissance in cancer therapy, driven largely by the breakthroughs in the understanding of how to leverage the immune system and harness it,” said Panna Sharma, CGI’s president and chief executive officer.

Sharma said that most oncologists aren’t yet using these diagnostic tools, but he hopes and believes it’s only a matter of time before these game-changing diagnostics become standard operating procedure at every cancer clinic.

“Awareness is key,” Sharma told Dr.China. “With these tools, the next 20 years will be amazing as far as the impact on patients. Maybe not my generation, but our kids will not be as afraid of cancer. It will be a manageable, chronic condition, a totally different world, and we’re living in the front end of this new world.”

Immunotherapy not a new science

Rita Shaknovich is a physician and scientist with more than 15 years of experience in both the clinic and the lab.

She has specifically focused on the genetic mechanisms of lymphoma.

Last summer, she was hired as CGI’s group medical director and vice president of hematopathology services. She told Dr.China that immunotherapy isn’t a new science.

“Researchers have been studying the idea of immunotherapy for nearly a half century. But all the years of research have begun to bear fruit,” she said. “As technologies mature and we understand more, we are able to reevaluate the old knowledge and manipulate biological systems.”

Immunotherapy’s basic concepts were there, she said, “But our ability to take human cells and manipulate them and reinfuse them were not there. The techniques to modify genes did not exist.”

Shaknovich adds the people who benefit the most from these scientific advances are the patients.

“We have more tools now, more options for patients,” she said. “The way I see these new options is that patients finally have viable alternatives to very toxic chemotherapy.”

But, she said, immunotherapy doesn’t work for every patient, and there are “many more pathways we have not explored. The complexity of the immune system activation is still not fully understood.”

New era for cancer patients

As a cancer patient, I’m more optimistic than I’ve ever been about what researchers are learning about cancer and how to fight it.

And I’m impressed and pleased that patient access and education as well as a sense of community between the patients, doctors, and companies that are making these drugs appear to be a priority in this sector.

Kamala Maddali, vice president of biopharma collaborations and companion diagnostics at CGI, has spent much of her life working to improve the cancer patient experience.

Maddali, who recently became a strategic advisor at GTCbio, an international biopharma communications company, has initiated multiple programs that connect patients and their families with oncologists, pharmaceutical and diagnostic companies, and patient advocacy groups.

She’s brought these groups together via partnerships, community events, panel discussions, and roundtables.

“My vision is to ensure that the patient’s voice is heard, and my goal is to help patients and pharma partners implement the right test or tests for the right patient and innovate a right drug for improving global community health,” Maddali told Dr.China.

The advent of immunotherapy, she suggests, represents an “evolutionary rebirth” for cancer therapy.

“Understanding patient tumor biology plays an important role in determining whether a patient is a suitable candidate for an immunotherapy,” she said.

For recently approved immunotherapies for non-small cell lung cancer, she explained, there’s a requirement to test for the presence of PD-L1, which is a ligand of PD-1, on the tumor in order to receive the drug.

“This represents a basic change in the way an oncologist treats and listens to a patient,” said Maddali, who encourages pharma partners to collaborate with clinical diagnostic labs to educate patients.

“A patient should be more knowledgeable about his or her disease and take the approach that, ‘I am not with the disease but the disease is with me,’” she said.

Colorectal cancer survivor optimistic

Erika Brown

Photo of Erika Brown

Erika Brown, a 14-year survivor of colorectal cancer, enjoyed a successful career as a corporate executive search professional until, at age 58, she received a diagnosis of late stage colorectal cancer.

Once she completed her treatment and went into remission, she changed her life and focused on the undeveloped niche of disease-specific patient empowerment.

She founded , an online community of “secret” groups on Facebook for colorectal patients, survivors, and caregivers.

Brown told Dr.China that immunotherapy is “changing the landscape” for colorectal cancer patients.

“Ten years ago, we didn’t believe a cure was in sight,” said Brown, now chief executive officer and founder of Paltown, a community-building and engagement organization that empowers patients through training, technology, and connection.

“Today, we have seen immunotherapy give hope to 5 to 6 percent of late stage colorectal patients,” she said.

Viral-based immunotherapies emerging

Another exciting sector under the immunotherapy tent that’s getting less attention but is still groundbreaking is viral-based cancer treatments.

Genelux Corporation, a biotech firm in San Diego, has developed a treatment using the oncolytic vaccinia virus that educates the immune system to mount a powerful and prolonged attack against a wide range of cancer types.

Genelux is conducting three ongoing clinical trials for its GL-ONC1, which is designed to destroy tumor cells and stimulate tumor-specific immunity.

Genelux recently initiated a trial to be conducted at Florida Hospital Cancer Institute to address late stage cancers for which there’s no available standard of care, with a particular focus on acute myeloid leukemia (AML).

“We are focusing on AML because our preclinical data showed that the virus can actively infect human AML cells,” explained Thomas Zindrick, president and chief executive officer at Genelux who was an executive for many years at Amgen.

Genelux is also conducting a phase II trial at Florida Hospital Cancer Institute and Gynecologic Oncology Associates (GOA) in Newport Beach, California, in recurrent ovarian cancer patients, which is seeing activation of long-lasting tumor-specific T-cell response and a favorable trend of durable response and disease control.

Genelux is also conducting a solid tumor trial for patients at UC San Diego’s Moores Cancer Center.

The early patient responses to Genelux’s technology are encouraging for a broad host of cancers, Zindrick told Dr.China.

He noted the future for virus-based treatments will likely be in combination with other therapies.

“Researchers are looking at the idea that combination therapies will ultimately be what are required to have a consistent efficacy against cancer,” Zindrick said. “Vaccinia-based immunotherapy is an ideal partner for combining with different types of cancer therapies, such as immune checkpoint inhibitors (ICIs). Our virotherapy could trigger immune activation, which could complement well with such ICIs, to counter immune defense from cancers.”

Immunotherapy may save your life

It’s been a long, strange trip for me since my first oncologist told me that my immune system has nothing to do with my cancer all those years ago.

Immunotherapy has come far. And, well, so have I. But I continue my quest for knowledge about cancer and ways my body can fight it.

I’m unfortunately not in remission. I’m in my fourth go-round with cancer. There are tumors in my lower abdominal area, but they’re not growing.

I’m in what we call “watch and wait.” Which means I watch the tumors, and wait, hoping they’ll never grow.

I’m still able to work and enjoy my family and friends. But I have chronic and often massive pain on the left side of my abdomen, from the bottom of my rib cage to my belt line.

The pain may or may not be related to my cancer. It likely is, but we can’t seem to verify that.

More than two dozen smart, well-meaning doctors have been unable to determine exactly what’s causing the often-debilitating pain, which prohibits me from taking long trips in a plane, train, or automobile.

I’ve tried literally everything under the sun to find out what’s causing the pain. But as anyone who knows me would tell you, I’m an optimist. I have a relentless love for life.

And while I’m still here, I want to inform and inspire as many fellow cancer patients as I can.

My patient advocacy has led me to do such things as host the , a global conference put on by GTCbio, featuring immuno-oncology leaders such as Scott Durum of the National Institutes of Health, Gordon Freeman from the Dana-Farber Cancer Institute at Harvard, and Holly Koblish from the Incyte Research Institute, discussing the latest discoveries in immunotherapy and how they’ll impact cancer patients.

I’m confident that CAR T, or perhaps some other immunotherapy on the horizon, could be my best hope of sticking around.

Immunotherapy could save my life someday. And perhaps yours, too.

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