Katie Kosko

Mary Sardegna was 2 years old when her parents noticed she wasn’t acting like herself. She was fatigued, had no appetite and often developed low-grade fevers. Then her stomach started to grow.

Several doctors thought she might have had the flu, and one suggested an enema to help with her bulging stomach. Eventually, a complete blood count (CBC) was performed, and it showed her white blood cell count was 525,000. A normal range is between 4,000 and 11,000 cells.

That’s when Sardegna’s parents were told that their daughter had chronic myeloid leukemia (CML), a type of blood cancer in which the bone marrow makes too many white blood cells. The bulge in her stomach was her white blood cells filling up her spleen.

“The only options in 1991 were bone marrow transplant, which had a 3% success rate, or a lifetime of medication,” recalls Sardegna, who lives in Laguna Hills, California. “My parents opted for the medication and were told by my doctor, ‘You’ll be sorry. There is no cure for this cancer. She’s going to die.’”

Sardegna was on interferon therapy for nine years, getting 70 shots a month. By 9 years old, she was injecting herself. “It was keeping the leukemia at bay, but it wasn’t helping it,” she says. “I was surviving, not thriving.” The medication made her tired, sometimes to the point where she would have to crawl across the floor to get to where she needed, and she developed a speech delay and learning disability.

“When I was in fourth grade, my mom got onto the internet — this was when it started to first come out — and she found a chat room where people were talking about a pill, STI-571. My pediatric oncologist had never heard of it,” Sardegna says.

STI-571 is now known as Gleevec (imatinib), a tyrosine kinase inhibitor (TKI) that targets BCR-ABL. This gene is formed on chromosome 22 when it fuses with chromosome 9; the abnormal chromosome is called the Philadelphia chromosome — a signature genetic aspect found in all patients with CML.

After researching the then-investigational drug, Sardegna’s mother found out about a clinical trial being conducted in Portland, Oregon, by Dr. Brian Druker in patients with CML. In 2001, they flew to Portland, and 11-year-old Sardegna became one of the few children allowed on the trial.

“Within nine months, I was considered cancer free,” she says. “I was less tired. I could walk and talk. I was thriving.”

Treatment advancements helped Sardegna, now 31, defy the odds. She was able to graduate college, get married and hold a job as a professional nanny. In January 2019, after 19 years on Gleevec, Sardegna safely came off treatment.

Targeted therapies like Gleevec, the first Food and Drug Administration (FDA)-approved TKI for CML, have not only transformed treatment but also turned the once-deadly disease into a condition that can be managed.

In addition to Gleevec, a first-generation TKI, four others are approved by the FDA: Bosulif (bosutinib), Sprycel (dasatinib) and Tasigna (nilotinib), all second-generation TKIs; and most recently, Iclusig (ponatinib), a third-generation TKI.

“Before we had TKI or stem cell trans- plant, the average life expectancy was seven years,” says Dr. Jerald Radich, a medical oncologist at Fred Hutchinson Cancer Research Center in Seattle. “With (these) new agents, life expectancy is pretty much normal.”

Unlike acute leukemias, CML is slow growing, survival is longer and about 80% to 85% of cases are diagnosed incidentally

during routine bloodwork, according to Dr. Jorge Cortes, director of the Georgia Cancer Center at Augusta University in Augusta, Georgia.

Often, patients don’t know they have cancer lurking inside their body because symptoms aren’t obvious and they mimic other conditions. CML may cause fatigue, weakness, bone pain, fever and loss of appetite.

Joan Clements experienced all of the above. In 2000, she was caring for her husband who recently had had surgery and helped her mother move from Arizona to California, so she wasn’t focused on her own health. She just knew something wasn’t right. While carrying boxes in the moving process, Clements noticed bruising on her body. That’s when she made herself a doctor’s appointment and brought him a list of 14 signs of leukemia. However, when she received the results of her blood test, the nurse told her everything looked fine.

Clements got sicker, dropping 28 pounds in just under two weeks. She demanded a CT scan with full contrast. But before she could proceed with the procedure, she needed bloodwork. “When I got home that day, my phone was ringing and it was the doctor saying, ‘You have to come back to the hospital right now,’” says Clements, now 78, who lives in Costa Mesa, California. “My white blood cell count was 375,000.”

Clements, then 59 years old, learned she had CML and was told she had two to four years to live because there was no cure. Instead of waiting helplessly, she went to City of Hope Comprehensive Cancer Center in Duarte, California. That’s where she learned about Gleevec. “I said, ‘I want this drug. I’m going to fight this beast,’” she recalls.

Clements celebrated her 19-year “cancer-versary” in December. She’s thankful to still be alive because of Gleevec, which she will remain on for the rest of her life, but it didn’t come without unpleasant side effects, such as nausea, vomiting, fatigue, gastrointestinal issues, leg cramps, brain fog, full body rashes and periorbital edema, or swelling around the eyes. “It looked like water balloons on my eyes,” says Clements, who co-founded the CML Buster Foundation and leads its U.S.-based CML Busters family support group. Although many of these side effects are common when first taking TKIs, in Clement’s case, most subsided and the ones that remain — gastrointestinal issues, nausea and brain fog — are manageable.

Compared with chemotherapy, targeted therapy is more effective and typically has fewer side effects. “Chemotherapy is a bomb. You throw it and try to kill all the bad guys,” explains Cortes. “These targeted therapies are specifically directed to where the bad guys are to spare the good. It’s more precise.”

TKIs are given as initial treatment for patients, and the advantage to having so many is that if a patient doesn’t respond to one, the dose can be increased or they can switch TKIs. For those who can’t take TKIs, interferon or chemo- therapy may be used. And, although patients with chronic phase disease are rarely treated with stem cell transplants, that may be an option, especially for younger patients.

When deciding how to treat a patient, an oncologist takes into account many factors, such as comorbidities, schedule, cost, age and whether the patient is of childbearing age.

In three randomized studies, second-generation TKIs were compared with Gleevec, and there is no difference in overall survival, according to Radich. However, second- generation drugs achieve a deeper response more quickly, and they tend to have less disease progression to an advanced phase.

“If you have an older patient and aren’t worried about them going into advance phase or having kids, then you would go with imatinib,” says Radich. “If it’s chronic phase, but the patient has a big spleen and has been sick or is younger and they want a response so they can get off drug, they might be good for second-generation TKIs.”

Monitoring patients regularly in CML is common to see how well therapy is working. A polymerase chain reaction test is typically done every three months by blood or bone marrow, and it looks for molecular responses — seeing the number of leukemia cells. Hematologic responses can be measured through a CBC to make sure blood cell levels return to normal. To test for a cytogenic response, or examining mutated chromosomes, a doctor can use a bone marrow sample.

Although there is an abundance of treatment choices for patients with CML, researchers are always looking for something better.

“Several medications are in development to address specific resistance, a mutation called T315I, and the most significant development is a targeted drug that is similar to the available therapies, but it has a unique mechanism of inhibition,” says Dr. Michael Mauro, a hematologist at Memorial Sloan Kettering Cancer Center in New York City.

That drug is called asciminib (ABL001), and it targets the ABL myristoyl pocket. It’s known as a STAMP inhibitor. Results of a phase 3 clinical trial showed that the therapy was safe and improved response rates over current options. Experts anticipate it to be approved by the FDA this year.

“Sometimes the mutations don’t allow the TKI to find its place where it can do its job,” Cortes explains. “By binding in a different place, which asciminib does, it allows it to work and override the resistance.”

A medication being developed in China, HQP1351, is being examined for its efficacy. Its focus is zeroing in on the T3151 mutation, and it could potentially be a therapy for those with CML whose disease becomes resistant to a first- or second-generation TKI.

In a phase 1 study, the drug K0706 has shown to be safe in patients who have received at least three prior lines of TKI therapy. It’s effective against wild-type and mutated BCR-ABL1 proteins.

And in Russia, researchers are examining PF-114, which also has activity against the T3151 mutation, and has shown good responses.

However, maybe most remarkable in the evolution of CML therapy is the emerging goal for patients to enter treatment-free remission, or TFR. It’s a decision that isn’t taken lightly.

In Sardegna’s case, when she asked her oncologist about it, she wasn’t met with open arms. Sardegna reached out to Druker, who has become a lifelong friend, for a second opinion, and he felt she was a great candidate.

To be considered for TFR, patients must reach a deep molecular response, which is defined as four to five reductions in disease burden, Radich explains. This needs to be sustained for at least two years.

Only about 40% to 45% of patients can stop treatment safely, according to Cortes, and about half will relapse.

Patients are monitored every month for the first six months with routine blood tests. Then follow-ups go down to every two to three months for the next two years, Mauro explains.

In September, Angelina Shilcosky was asked by her doctor whether she wanted to stop therapy because she had been in complete remission for a few years. “I was nervous at first, but it took stress off my mind,” says Shilcosky, 43, who received a CML diagnosis at 27 when she was three months pregnant and had a 2-year-old at home. “My mom and mother-in-law told me to stay on it. But I trust my oncologist, and he said if numbers (started) to change, we (would) go back on it.”

Shilcosky feels like she’s forgetting to do something each night because she popped a Gleevec pill daily for 14 years, but she feels thankful to be off it and gives back to the CML community by participating in the Leukemia & Lymphoma Society’s Light the Night campaign each year.

A downside to TFR is the potential for withdrawal symptoms, which Sardegna experienced. “Around six months after I stopped treatment, I got excruciating muscle pain,” she says. “It felt like my muscles were turning over.”

About 10% to 30% of patients who stop TKI therapy report withdrawal symptoms like bone pain and/or rash. However, most can be managed through over- the-counter medications, according to the Leukemia & Lymphoma Society.

“It’s important to remember that it’s a marathon, not a sprint,” Mauro says. “But it should be one where side effects are minimal and response is on target hitting milestones.”

For more news on cancer updates, research and education, don’t forget to

Articles

Patients with chronic myeloid leukemia are living longer, some even stopping treatment, thanks to a plethora of targeted therapies.

Knocking Out Chronic Myeloid Leukemia with Precision

Finances can become the deciding factor in which treatment a patient with cancer chooses to receive, where they receive it and if they can keep on that treatment regimen for an extended period of time.

It’s crucial for all patients to find the right treatment team and that may mean traveling further from home for days or even weeks. For patients with mesothelioma, being treated at a large academic cancer center is key since this disease is rarer than other cancer types.

Certain organizations across the country have financial assistance programs to help. For instance, Cancer

, the leading national organization providing free, professional support services and information to those affected by cancer, has a new program that exclusively offers assistance to patients with mesothelioma.

Once a patient is interviewed by phone and completes a financial application, they are eligible to receive a portion of grant money from the Mesothelioma Transportation Assistance Program that can be used for services such as air travel to a treatment facility, lodging and airfare.

Francine Shuman is thankful she qualified for this help as she has to travel from Augusta, Georgia, to Atlanta, to receive treatment at Winship Cancer Institute of Emory University, which requires driving two hours one way from her home to the cancer center, as well as staying overnight a few days in a hotel. “I’ve got bills to pay. I can’t afford it,” she says.

Shuman received a peritoneal mesothelioma diagnosis in February 2020 and after undergoing chemotherapy, she recently had surgery to remove the cancer that develops in the lining of the abdomen. She believes her cancer was caused by years of inhaling talcum powder that she used on her three daughters as babies. Talc is a mineral that can absorb moisture and because it’s found in close proximity to asbestos — a known carcinogen — in the earth, there is concern that talc can become contaminated.

After calling several organizations, Shuman finally connected with Cancer

and through the program, Shuman received a $1,000 grant for expenses. “I was told I would get the loan and I wouldn’t have to pay it back. And I just thanked the Lord because I didn’t know how I was going to get back and forth,” she says.

To initiate the process for the Mesothelioma Transportation Assistance Program, the person who received the diagnosis or a caregiver can call Cancer

’s HOPEline at 1-800-813-4673 or email Charlotte Ference, a social worker, at 

A new grant program offers financial assistance for patients with mesothelioma who must travel for cancer care.

Making Cents of Mesothelioma

In August 2014, Russell Lamkins was given six months to a year to live after learning he had malignant mesothelioma. More than six years later, he is traveling the country in his motor home with his wife and, although the cancer has slowed him down, he says he feels good.

Lamkins credits this success to the care he has been receiving on a clinical trial at Moffitt Cancer Center in Tampa, Florida, which is about two hours north of his home in Bonita Springs.

“(Moffitt) never promised anything. They explained that it was all experimental,” recalls Lamkins, now 74. “My wife and I went back to the cancer specialist in town and all he could say was, ‘If you want to be a guinea pig ... fine, or we can start chemotherapy next week.’”

Lamkins stuck with Moffitt and was the second patient to enroll in a clinical trial in 2016 that offered transarterial chemoperfusion, a therapy that involves delivering a high concentration of medicine to the diseased tissue lining in the lungs. He began this after his disease progressed despite standard chemotherapy and immunotherapy.

“I thought, what did I have to lose? Maybe this is the miracle drug. If not, it’s going to help someone down the line,” he says.

Mesothelioma is an aggressive type of cancer that forms in the lining of the lungs, abdomen or heart. Considered rare, the number of mesothelioma cases diagnosed in the United States is about 3,000 each year.

It’s most commonly seen in men, white or Hispanic people and those who are older. The biggest risk factor for developing mesothelioma is exposure to asbestos, a group of minerals that occur naturally as bundles of tiny fibers that are found in the earth’s soil and rocks. Those fibers become dangerous when inhaled, as abestos is a known carcinogen. People most at risk for asbestos exposure include miners, factory workers, shipbuilders, insulation manufacturers and installers, railroad workers and construction workers. Lamkins had been in construction since he got out of the Marine Corps in 1967.

“We did all phases of construction ... roofing, drywall, insulating, and then remodeling of homes which involved tearing things apart that we later found out had asbestos in it,” he says.

Other potential risk factors include exposure to zeolites, minerals chemically related to asbestos; high doses of radiation to the chest or abdomen for other cancer treatment; and a mutation in the BAP1 gene, however, this is rare, according to the American Cancer Society.

Although Lamkins didn’t experience any symptoms, people with mesothelioma may show signs such as fever, excessive sweating, fatigue, weight loss and loss of appetite. However, symptoms can vary depending on the type of disease. Pleural mesothelioma, occurring in the chest, is most common, making up 70% of cases, said Dr. Jacques Fontaine, a medical oncologist at Moffitt Cancer Center. Peritoneal mesotheliomas begin in the abdomen and, very rarely, mesotheliomas can occur in the covering the heart or in the covering layer of the testicles. For patients whose disease starts in the chest, signs may appear as shortness of breath, cough, pain inside the chest or lower back, hoarseness and trouble swallowing.

In cases where the disease arises in the abdomen, patients may experience belly pain or swelling. Francine Shuman thought her protruding belly was a sign of old age. Her belly began to swell and she dropped 20 pounds quickly. “I had all the symptoms,” says Shuman, 67, of Augusta, Georgia. Not thinking it was cancer, Shuman ended up in the emergency room from dehydration brought on by not eating because of sciatica pain. A 4-centimeter lump was discovered and a biopsy revealed peritoneal mesothelioma, which she believes was a result of inhaling talcum powder that she used on her three daughters when they were babies. “I was told that only 600 people a year get this,” says Shuman.

Talc is located in close proximity to asbestos, therefore the talc could be contaminated with asbestos fibers. In recent years, there has been controversy surrounding talcum products and cancer risk, including mesothelioma.

Receiving a proper diagnosis can be challenging for patients since mesothelioma can mimic other diseases and is often mistaken for lung cancer, according to Fontaine. “It can take four to six months at the time of presentation to diagnose.”

Patients need to understand the importance of being seen at a high-volume cancer center, where more cases of mesothelioma are seen, says Dr. Daniel Sterman, director of the pulmonary oncology program at NYU Langone Health. He suggests interviewing a few oncologists before making a decision on where to be treated.

“This is a disease for which we have no cure,” Sterman says. “Even at its earliest stages, there is no proven curative therapy but that doesn’t mean therapies aren’t effective.”

Surgery, Combination and Tumor Treating Fields

Since staging of mesothelioma is complex, patients may undergo not only a CT or PET scan, but also an MRI of the chest, lymph node scanning and exploratory surgery, Sterman explains. Three major cell types can affect a person’s treatment regimen — epithelioid, sarcomatoid or a combination of both. More than half of cases are epithelioid and these patients respond best to chemotherapy. They also have the best prognosis.

About 10% to 20% of cases are sarcomatoid, which has the worst prognosis. While chemotherapy shows little response with this type of cell, immunotherapy is proving to be effective.

The type of treatment will depend on a patient’s stage, location of the cancer, subtype, whether it has spread and performance status or level of fitness. Surgery or systemic therapy, such as chemotherapy and immunotherapy, with or without radiation are treatment options for patients. Some may also choose no therapy at all, but rather receive palliative care to improve quality of life and control pain. About 25% of patients, those who are typically older with other health issues, opt for this, explains Fontaine.

Surgery to debulk mesothelioma is aggressive. “We cut the ribs and go in to remove the lining around the heart and then rebuild it with synthetic mesh,” says Fontaine. “It takes several hours of surgery plus a week stay in the hospital and a long time to recover.”

In addition, surgery alone may not be able to completely remove the cancer. Therefore, combining surgery with chemotherapy, immunotherapy, or a combination of both, either before or after surgery should be considered, Sterman suggests.

Following her diagnosis in February, Shuman received eight chemotherapy treatments and gained 32 pounds from the steroids she was put on. “It made me depressed,” she says. “By the eighth chemo treatment I could barely walk. This broke me down. I didn’t want to live anymore.” Shuman will soon undergo surgery to help get rid of her cancer.

“Although many patients with early-stage mesothelioma are referred for surgical resection, we still don’t know that surgical resection is the right thing to do,” Sterman says.

The MARS 2 clinical trial will examine how effective surgery is alone versus surgery and systemic therapy in more than 300 patients. Enrolling participants in the United Kingdom, researchers will investigate overall survival, safety, quality of life and cost in patients with pleural mesothelioma.

“After enrollment is complete, there will be two years of follow up so the results of the trial will be available at the end of 2022,” says chief investigator Dr. Eric Lim, a thoracic surgeon at Royal Brompton Hospital in London. “We don’t know if there is any benefit to the operation and that’s why this trial is important.”

Most exciting in the treatment of mesothelioma is the October approval by the Food and Drug Administration (FDA) of Opdivo (nivolumab) and Yervoy (ipilimumab), two types of immunotherapies, to treat adult patients with malignant pleural mesothelioma that can’t be removed by surgery — the first regimen approved for mesothelioma in 16 years.

The approval was based on the findings of a phase 3 clinical trial that included more than 600 patients who either received the immunotherapy combination or standard of care chemotherapy. Researchers saw a median overall survival of 18.1 months with the combination compared with 14.1 months with chemotherapy. The two-drug combination also reduced the risk of death by 26%.

“So far these are the most impressive results achieved,” Lim says. “All the other treatments have shown to be ineffective, so to reduce the risk of death by 26% is huge.”

Immunotherapy is an attractive option as it may have fewer side effects than chemotherapy. Patients who receive it have less vomiting and fewer kidney problems. It also doesn’t require a patient to sit for hours in an infusion center. However, patients who have immune diseases, such as arthritis, lupus and thyroid disease, can’t receive it.

In addition, data from the phase 2 DREAM trial based in Australia is promising for patients with pleural mesothelioma. In more than 50 patients, immunotherapy combined with chemotherapy was superior to chemotherapy alone.

The phase 2 clinical trial that Lamkins is part of was presented during the Society of Interventional Radiology 2020 Annual Scientific Meeting. Interim results of the study showed a median overall survival rate of 8.5 months, a disease control rate of 70.3% and minor side effects, such as mild nausea, with transarterial chemoperfusion.

A potential new second- or third-line treatment option is being studied in the form of gene therapy. The INFINITE trial is looking at an investigational drug in combination with anti-inflammatory and chemotherapy drugs. The therapy is called Adenovirus-Delivered Interferon Alpha-2b, and in earlier clinical trials it extended patients’ lives by 17 months. “This is what I’ve been working on for the last almost 25 years of my career ... what are other ways to stimulate immune responses which can synergize with chemotherapy and immunotherapy,” Sterman says.

There also is excitement in Tumor Treating Fields (TTFields), which uses low-voltage electricity to prevent the cancer from growing. It’s FDA approved in combination with Alimta (pemetrexed) with cisplatin or carboplatin. “It’s like a magnet. These electrical currents screw up polarization and the cells can’t grow or duplicate,” Fontaine says.

Chimeric antigen receptor (CAR)-T cell therapy and PARP inhibitors are being explored for the treatment of mesothelioma, but these clinical trials are very early.

“There has been tremendous scientific progress. Although we don’t have a cure, I remind patients that for people with high blood pressure, rheumatoid arthritis and diabetes, we don’t cure those diseases either,” Sterman says. “We manage them. We turn them into chronic diseases. We can prolong and improve quality of life with these advances.”

Despite feeling beat down by chemotherapy, Shuman remained positive for her daughters, 13 grandchildren and one great-grandchild. She also turned to her faith. “I believe in the power of prayer. I always have,” she says. “Had I known these were symptoms of cancer, I would have seen my doctor sooner.”

Lamkins continues to travel, hitting all but two of the 50 states — Hawaii and Alaska — and changed his diet by eating organic and eliminating sugar. His goal is to outlive a man who lived for 11 years after a mesothelioma diagnosis. Plus, Lamkins joked, “I have a list of stuff that my wife tells me I have to get done, so as long as I have a list, I’ve got to keep chugging along.”

Patients with mesothelioma are living longer thanks to new drug combinations – including the first FDA-approved regimen in 15 years.

New Drug Combinations Are Helping Patients With Mesothelioma Live Longer

Hope, knowledge and direction. Bonnie Addario’s goal is to make sure every newly diagnosed patient with lung cancer has all three to empower themselves and their caregivers.

In 2004, Addario received a stage 3b lung cancer diagnosis. As a wife, mother and grandmother, she didn’t want to give up — despite being given a 16% chance to live. For months, she received a chemotherapy regimen weekly and radiation daily to shrink her tumor.

Then she underwent a 14-hour surgery performed by three surgeons — thoracic, heart and vascular — each taking his turn along the way, followed by more radiation. Addario was then declared cancer free. Two years later, she was invited to speak with others like herself at a support group — and what she saw was life changing.

“Picture a large room with gray walls, gray carpeting, gray drapes and gray folding chairs positioned around a gray, oblong table — everything looked gray beneath the dull lighting. Even the people sitting there before me appeared gray. Nobody was living in that room,” wrote Addario in her upcoming book, “The Living Room: A Lung Cancer Community of Courage.”

“Instead of offering the support they’d come for, this place only reinforced the fact that they were dying. A support-group setting should be a place where patients come to live, not die.”

The book has been a life project for Addario, who is all about taking a personal approach to cancer care. Throughout the pages of her book, readers get to know 21 people who have survived advanced lung cancer, including a husband and wife both diagnosed with lung cancer, a man who rode 3,400 miles on his bike in honor of his mother who died from the disease in 2017 and a young woman who fought for her life after having no risk factors or family history of lung cancer. Their stories tell how they managed to find the courage, resources, spirit and faith to keep momentum while fighting a devastating disease.

Addario also shares in the book very personal details of her life and diagnosis, along with words of wisdom from some of the world’s leading lung cancer experts on various topics such as screening.

After that support group, Addario also realized that she wanted to create a cheerful place for thrivers to come together. And she did just that, developing a real-life Lung Cancer Living Room that offers education and support and has helped countless patients with lung cancer find hope.

“They are my new heroes, the very definition of what it means to be brave,” wrote Addario, a fierce advocate for lung cancer survivors through the GO2 Foundation for Lung Cancer. “They don’t give in and they don’t give up, men and women who come to the Living Room hopeless and leave hopeful. So come right in. Join us and make yourself comfortable. Our session is about to begin.”

Bonnie Addario, a 16-year lung cancer survivor, shares a message of hope and invites you to ‘The Living Room.’

Katie Kosko

Knocking Out Chronic Myeloid Leukemia with Precision

Making Cents of Mesothelioma

New Drug Combinations Are Helping Patients With Mesothelioma Live Longer

All Are Welcome: A Real-Life Lung Cancer 'Living Room'

Latest News