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Keytruda® Offers New Hope for Mesothelioma Survivor Paul Zygielbaum


Mesothelioma survivor Paul Zygielbaum

For more than a decade, Paul Zygielbaum had beaten the odds, but now he was certain his time was up. He’d survived four surgeries and three chemotherapy regimens since being diagnosed with peritoneal mesothelioma in 2004, but by last summer his tumors had spread to his chest and grown massively, he had difficulty breathing and he had lost a significant amount of weight.

A retired aerospace engineer and businessman, Zygielbaum methodically began making his final preparations. He spoke with his financial and tax advisers. He wrote goodbye notes to several friends. And with the help of his wife, Michelle, he picked out his own coffin.

“I’m dying,” he thought. “I’ve had a really fulfilling life, but this is the way it is. It’s my time. I survived 12 years after the diagnosis. That’s a pretty good run.”

Paul Zygielbaum’s run isn’t over yet.

Keytruda® Offers New Hope

Ten months after he began infusions of a new immunotherapy drug known as Keytruda® (pembrolizumab), Zygielbaum’s tumors have either disappeared or shrunk, his appetite has come back, and his blood tests are nearly normal for the first time in a dozen years. He’s resumed doing chores around his house in Santa Rosa, Ca., practicing yoga, and taking trips with his family.

He’s also resumed his activities as an advocate for banning asbestos in the United States and as a champion of patients with asbestos-caused diseases. In April, he served as moderator for a panel where he and other mesothelioma patients discussed their experiences with Keytruda®. The panel was part of the Asbestos Disease Awareness Organization’s (ADAO) annual conference in suburban Washington, D.C. Then he and his wife took a trip to Yosemite National Park in northern California.

“I’m back to living a normal life,” Zygielbaum, now 65, told the Mesothelioma Cancer Alliance. “I had said my goodbyes – I was ready to go. All of a sudden here I am. Now I’m doing stuff. I’m busy.”

“It’s astounding,” he said. “I feel like I am the beneficiary of a miracle.”

Zygielbaum isn’t alone is touting the benefits of a potentially-groundbreaking new wave of immunotherapy drugs, including Keytruda®, aimed at unleashing the body’s immune system to fight off cancer cells. Late last year, for example, former President Jimmy Carter, who has stage-four melanoma, made national news when he credited infusions of Keytruda® for shrinking his brain tumors completely.

The Obama-Biden Moonshot

The immune system is the body’s natural defense against disease. It sends types of cells called T cells throughout the body to detect and fight infections and diseases—including cancers like melanoma and mesothelioma. But cancer cells can trick the body’s immune system and hide from the immune system by taking control of the PD-1 pathway – preventing T cells from attacking cancer cells. Keytruda® works by blocking the PD-1 pathway.

In short, Keytruda® helps the immune system do what it was meant to do: detect and fight cancer cells, according to the drug’s manufacturer, Merck.

Immunotherapy has the potential to revolutionize the way doctors fight cancer and generate $35 to $70 billion dollars in sales in 10 years, according to a report in Time magazine. There are currently 3,400 clinical trials involving immunotherapy taking place in the United States and numerous others overseas, including some involving mesothelioma patients.

Indeed, immunotherapy is a key part of the Obama Administration’s $1 billion “moonshot” aimed at accelerating cancer research and making 10 years’ worth of progress in the next five years. The effort is being led by Vice President Joe Biden, whose eldest son died of cancer last year.

So far, Keytruda® has been approved for treatment of melanoma and non-small cell lung cancer, the most common form of lung cancer. In clinical trials, it’s also shown promising results as a treatment for mesothelioma, according to multiple studies presented at the American Association for Cancer Research conference in Philadelphia last year.

A New Wonder Drug?

Keytruda® doesn’t work for all patients or all types of cancer. And it is expensive – the drug costs about $12,500 a month per patient, or $150,000 for a full year. Nonetheless, physicians and patient advocates are cautiously optimistic that it could eventually save or prolong the lives of thousands of people who been diagnosed with mesothelioma, a rare and fatal cancer caused by exposure to asbestos.

“Keytruda® is this new, for some people, wonder drug,” said Dr. Arthur Frank, a professor of public health at Drexel University in Philadelphia, speaking in April at the annual conference of the ADAO.

“There are some cancers for which it (Keytruda®) has not proven particularly useful,” Frank continued. “Interestingly, the ones for which it has shown to be of some use, both melanoma and now mesothelioma, actually share some altered genes. So in terms of its ability to cause a good response in terms of patients who get it, it’s is these cancers with unstable genes it seems to work best with.”

Keytruda® doesn’t generally have an instant impact. “It often can take a number of months before there is a response,” Frank said. “It is not one of those drugs that necessarily work immediately. You may have to take it for a while.”

“It suffers from one other problem that is true for many of the new therapies we have these days,” he added. “It is extraordinarily expensive. That is a special issue that needs to be dealt with – at least in a country like the United States with the amount of monies we have. Even given the expense it is something that people who are appropriate to get it ought to get it.”

Linda Reinstein, president of the ADAO, also expressed both hope and caution.

“During the past years, cancer immunotherapy therapy clinical trials have given patients hope that a cure for mesothelioma is on the horizon,” Reinstein told the Mesothelioma Cancer Alliance. “While excitement builds for Keytruda®, it’s important to look closely at the data, as some patients have had excellent results, others did not benefit at all.”

A Terrible Journey

Paul Zygliebaum’s history with asbestos began more than six decades ago.

He was first exposed to asbestos when he was a very small child, from the dust-covered work clothes his father brought home from his job as a maintenance worker in Los Angeles. The elder Zygielbaum had been a Jewish partisan leader in Europe during World War II and spent much of his career in aerospace and intelligence work.

Paul Zygielbaum was a student at the California Institute of Technology in 1970 and worked as a technician insulating a steel tank using asbestos cloth. Additional asbestos exposure occurred several years later while fixing wall damage in a house he and his wife had purchased. In 1978, Zygielbaum experienced further exposure, this time to undisclosed asbestos, while working in a power plant.

He first noticed symptoms in 1998 while living in Amsterdam, Zygielbaum said. Always lean and athletic, he was looking heavier and was fatigued. By 2002, the symptoms got worse; there was so much fluid in his belly that “I was walking like a pregnant woman,” he said.

He was diagnosed with peritoneal mesothelioma in 2004, beginning what he referred to as “a terrible journey,” in which he endured four surgeries, three chemotherapy regimens, and the disease eventually spread to his chest.

By 2015, he needed a break from the constant medical treatments. He and his wife went on an archeological trip to French Polynesia with some friends. The trip was supposed to be an adventure, but it turned out to be an ordeal for Zygielbaum. He had trouble catching his breath and was fatigued while climbing through the jungle. He also lost his appetite.

When he returned to the United States, he received bad news. A scan taken in July 2015 showed his tumors had grown massively over the past three months, explaining his fatigue. The tumors had also spread to his chest and into the lungs. “So now I had lung cancer,” not just mesothelioma, he said.

The nearly 6-foot Zygielbaum’s weight dropped from 192 pounds to 167 pounds. “I looked like a stick,” he recalled. “We were getting down to the end. I was very weak and eating very little.”

His oncologist suggested he try immunotherapy, but told Zygielbaum he might have to pay for the treatment himself. “There’s nothing to lose, let’s try it,” Zygielbaum told his doctor.

He had his first Keytruda® infusion on July 15, 2015. About the same time, Zygielbaum’s 39-year-old son asked his father to marry him and his long-time girlfriend. (Zygielbaum has a license to perform marriage ceremonies.) The wedding was set for August 1.

“I figured I had a few weeks left,” Zygielbaum recalled. He made it through the ceremony, but a photo taken that day shows him looking unhealthy with a gray pallor.

Zygielbaum had his second infusion of Keytruda® on August 3. By this time, he could barely breathe and was running a fever. The nurse practitioner who administered the Keytruda® ordered him to the hospital, where Zygielbaum was diagnosed with pneumonia.

Then everything suddenly changed.

Signs of Improvement

“I started to feel better – not just like I was recovering from pneumonia, which I had had before but better,” he recalled. He turned to his wife Michelle and said, “Something in my body has changed.”

When he got home from the hospital, he remembered, “I got my appetite back. I started to feel like I could do things instead of sitting around in my pajamas.” A scan in late August 2015 showed the tumor growth had stopped. He began to put back the weight he had lost (his weight is now a stable 185 pounds). He was able to do routine chores around the house, such as taking out the garbage.

By last Thanksgiving, Zygielbaum was feeling more like his old self. “I was feeling better and better,” he said. “The tumors had receded quite a bit in my abdomen and chest,” he said.

Like other patients, Zygielbaum receives a Keytruda® infusion every three weeks. He recently received his sixteenth such infusion, and he’s also had some radiation treatment to help shrink one large tumor. He said that his tumors are no longer changing – they are no longer shrinking, but they are not growing either. “I have a good quality of life now,” he said, adding that he has had only very minor side effects, including some fatigue, acne and a puzzling aversion to red wine.

Because he has lung cancer as well as mesothelioma, and because Keytruda® has been approved by the U.S. Food and Drug Administration (FDA) for treatment of lung cancer, Medicare covers most of the cost in Zygielbaum’s case. But for others with mesothelioma alone, the costs of undergoing Keytruda® immunotherapy may be out of reach. The discussion over costs and benefits is only likely to accelerate as more new immunotherapy drugs become available.

“Although the FDA approved Keytruda® for the treatment of patients with melanoma and advanced squamous non-small cell lung cancer, it has not been approved for mesothelioma, thus making the drug prohibitively expensive to the patients seeking treatment outside of a clinical trial,” said the ADAO’s Reinstein. She added, “Keytruda® has opened the conversation about cancer treatments that may not be curative, but that improves the patient’s quality of life.”

A Living Symbol of Hope

Asbestos remains legal in the United States despite an overwhelming consensus among scientists that it is a carcinogen, and an estimated 15,000 Americans die from mesothelioma and other asbestos-caused diseases each year. In many ways, Paul Zygielbaum’s mesothelioma survivor story for more than a dozen years after being diagnosed and his recent experience with Keytruda® immunotherapy have become symbols of hope to patients and physicians within the mesothelioma community.

As one indication, Zygielbaum received a standing ovation at the ADAO conference this year when he recounted his 12-year medical battle with mesothelioma and his recent experience with Keytruda® immunotherapy. As another, there was his chance encounter at the conference with Dr. Raja Flores, chairman of Thoracic Surgery at Mount Sinai Medical Center in New York, who helped pioneer the use of intraoperative chemotherapy for mesothelioma.

Dr. Flores was about to go on stage to speak about progress in treating mesothelioma and other asbestos-related diseases. Zygielbaum, who was standing nearby, turned to Flores and said, “I don’t remember which conference it was, years ago, but you said that a diagnosis of mesothelioma was no longer a death sentence. I will never forget that moment.”

Flores put his arm around Zygielbaum, hugged him and responded, “And you are living proof!”