Katie Kosko

In 1999, Meg Lowry learned that her platelet count ran high after having routine bloodwork done during an annual physical exam. Her primary care physician told her not to worry. 

Eight years later, after her annual physical, she received a life-changing phone call from her doctor’s office. 

“The nurse said, ‘We need to see you at 8 a.m. tomorrow.’ When I went in, I was told that my platelet count was 890,000 and that I needed to start taking Hydrea (hydroxyurea),” Lowry recalls. 

Normally, platelet counts range from 150,000 to 400,000 platelets per microliter. Although Lowry was hesitant at first, she followed the instruction to take the chemotherapy medication. At the same time, she developed painful lesions on her skin. 

“They almost looked like mosquito bites. They were raised and itchy, then would scab over and stay on my skin for weeks,” she says.

Lowry saw a dermatologist who biopsied the lesions and was told she had Sweet syndrome, a rare skin condition characterized by infiltration of neutrophils (a type of white blood cell) that can be triggered by an infection, an illness such as cancer, medication and sometimes even pregnancy. She was given cortisone and told she would need to see an oncologist. Trying to wrap her head around those words, Lowry called her friend who works at The University of Texas MD Anderson Cancer Center in Houston to share what she was told. Within five days, Lowry had an appointment with the head of the leukemia department. In January 2008, Lowry, who was 56 years old at the time, received a diagnosis of essential thrombocythemia (ET), which is a rare blood cancer and one of three main types of myeloproliferative neoplasms (MPNs). She was told to continue the Hydrea and see an oncologist every six months.

The three main types of MPNs are ET, polycythemia vera (PV) and myelofibrosis (MF). ET is caused by the bone marrow producing too many platelets, the part of the blood needed for clotting; PV occurs when the bone marrow produces too many red blood cells; and MF is characterized by the buildup of scar tissue in the bone marrow. It is often found during routine bloodwork, usually in its early phases. Symptoms of the group of incurable diseases include anemia, fatigue, pain or fullness in the belly from an enlarged spleen, prolonged bleeding from minor cuts, shortness of breath and weakness. It can also less commonly cause blood clots. It wasn’t until 2014, however, that Lowry felt her condition was more dire. She began to run a low-grade fever daily, had brain fog, fatigue, joint and muscle aches, nausea and night sweats. 

Meg Lowry's platelet count in May 2015 was 3.1 million — considerably higher than the normal range of 150,000 to 400,000. 

“I got to the point where I carried a thermometer in my purse. I was always pushing through,” she says. In May 2015, Lowry left her home in Austin, Texas, and headed for MD Anderson Cancer Center yet again, where her labs showed that her platelets were 3.1 million and that her hemoglobin level had dropped.

“The doctor told me, ‘I think you have leukemia or myelofibrosis,’” Lowry recalls. Ten days later, she learned that her ET diagnosis had progressed to accelerated MPN and that she was positive for an IDH1 mutation. MPN in the accelerated phase is not as common as the chronic phase and is defined by 10% to 19% myeloid blasts (a type of immature white blood cell) in the peripheral blood or bone marrow, according to Dr. Aaron Gerds, an assistant professor of medicine and deputy director for clinical research at Cleveland Clinic Taussig Cancer Institute in Ohio. Accelerated-phase MPN is often a precursor to blast-phase MPN, also referred to as acute myeloid leukemia (AML). Blast-phase MPN is associated with 20% or more myeloid blasts. 

“Depending on the analysis, the lifetime risk for ET to turn into blast-phase disease is less than 5%,” Gerds says. “(For) MF, (it) is much higher — 10% to 20%.”

Progression can only be confirmed through blood or bone marrow biopsy analysis. Typically, patients will have significant blood changes — decreased hemoglobin, a rapid platelet drop and a rapid rise in white blood cells, explains Dr. Abdulraheem Yacoub, an associate professor of medicine in the Division of Hematologic Malignancies and Cellular Therapeutics and clinical director of the Ambulatory Hematology Clinics at University of Kansas Medical Center in Kansas City. Patient symptoms may also worsen, or new symptoms will develop, such as drenching night sweats, weight loss and an enlarged spleen. 

“Usually transformation is gradual, not sudden,” Yacoub says. “Patients considered high risk will be watched closely with labs every one to three months. So even at this rate, you can still catch it early as it happens.”

Although there is no specific predictor of which patients with MPNs might progress over time, certain patients are at higher risk based on specific disease features, i.e., having a primary diagnosis of MF and testing positive for genetic mutations such as IDH1/IDH2, RAS and TP53. 

“You can test for mutations at any time,” Gerds says. “Generally, it’s advised to test, if you can, a large panel of genes not only for driver mutations, but also others that can be important in prognosis.”

The only way to potentially cure MPNs in accelerated phase or blast phase is through an allogeneic stem cell transplant, which uses healthy blood stem cells from a donor to replace diseased or damaged bone marrow. Without a transplant, other therapies are short-lived — effective for just a few months — according to Dr. Naseema Gangat, an associate professor of medicine at Mayo Clinic in Rochester, Minnesota. However, based on age, functioning and comorbidities, not every patient is a good candidate for stem cell transplant.

“The majority of patients are about 65 years of age and not in the position to tolerate aggressive treatment,” Gangat says. “If they are fit and (younger than) 70 years old, I would go with intensive AML chemotherapy, followed by transplant.” 

Even with transplant, two-year overall survival rates (the time from treatment that a patient with cancer is still alive) range from 29% to 75% for advanced MPNs. With limited treatment options, researchers have begun to borrow therapies from other blood cancers, particularly molecularly targeted therapies, to see how well they work for these patients. Clinical trials, although small because of the available patient population, are being conducted for efficacy and safety. In one study, Venclexta (venetoclax), an inhibitor of the BCL2 protein, was combined with a hypomethylating agent (which can trigger the reprogramming of tumor cells), such as Vidaza (azacitidine) or decitabine, in patients with blastphase MPNs. 

The study included 32 patients with a median age of 69, and two-thirds of them had a mutation or three or more chromosomal aberrations. Twenty patients had not received prior therapy. A complete response (defined as a disappearance of all signs of cancer) was achieved by 14 patients and was more likely in those who did not have preleukemic PV/post-PV myelofibrosis. Six of these patients were able to go on to receive an allogeneic stem cell transplant.

“Even though these new approaches are available, they are being used more as a bridge to allogeneic stem cell transplant. And if you’re an unfit patient, they improve your quality of life,” says Gangat, who was an author on the study. Another study, presented at the 2021 annual meeting of the American Society of Hematology, included 39 patients with blast-phase MPNs and found that they responded best to the combination of Venclexta and a hypomethylating agent compared with intensive chemotherapy or a hypomethylating agent alone. Patients were divided into four groups to receive one of the following: Venclexta/hypomethylating agent; fludarabine, high-dose cytarabine and granulocyte-colony stimulating factor; a hypomethylating agent only; or daunorubicin and cytarabine. 

“What’s more important is understanding accelerated- and blast-phase disease and targeting it in innovative ways,” Gerds says. “There are patients who can have ET for decades, and then all of a sudden, it turns into blast-phase disease. The pattern of mutations is very different. Mutations in genes like TP53 and NRAS seem to be key with late disease progression, whereas mutations in EZH2 and RUNX1 are key players in those who progressed more (quickly) after diagnosis.” 

Unfortunately, there are no specific medications to target many of these mutations, explains Yacoub. Yet other mutations seen in MPNs can be targeted. For example, researchers are exploring the use of Rydapt (midostaurin), which targets the FLT3 mutation. This mutation appears in approximately 3% of patients with MPNs in accelerated phase or blast phase. Rydapt is already approved by the Food and Drug Administration (FDA) for the frontline treatment of patients with AML.

IDH1 and IDH2 are also potential targets because up to 20% to 25% of patients with accelerated- or blast-phase MPNs have one of these mutations. Tibsovo (ivosidenib), an IDH1 inhibitor, and Idhifa (enasidenib), an IDH2 inhibitor, are being examined in combination with chemotherapy or a hypomethylating agent. Lowry was lucky enough to arrive back at MD Anderson Cancer Center when she did because she was one of the first patients to join a clinical trial in June 2015 that investigated Tibsovo and which ultimately led to the FDA approval of this agent. 

“Before this, I was constantly nauseated,” Lowry says. “This was the best I’ve felt.” Within a year of starting the trial drug, her platelets were in normal range and all her symptoms disappeared. Lowry calls her response miraculous. “It gave me my life back, my energy back,” she says. “I try to live in gratitude.”

In addition to these approaches, research is being conducted using Janus kinase (JAK) inhibitors in combination with other medications because MPNs are caused in a large part by mutations that drive the JAK-STAT growth signaling pathway. For instance, clinical trials have examined Jakafi (ruxolitinib) plus decitabine. But patient responses have been modest, Gangat explains. The immunotherapy medication Keytruda (pembrolizumab) is also under investigation in an early clinical trial for patients with advanced MPNs, including accelerated phase and blast phase, who did not respond to therapy with a hypomethylating agent. Because so much research is evolving, Yacoub notes that it’s crucial for patients to be their own best advocates. 

“Sometimes you might have to travel for a clinical trial that would be best suited for your diagnosis,” he says. “I strongly recommend that patients seek care under the care of experts in a center that can deliver a transplant.” 

The ultimate goal, says Gerds, is to help patients with accelerated-phase and blast-phase MPNs live better and longer lives. “I think the key is finding treatments that can improve remissions but don’t cause a lot of toxicities,” he says. “We need to focus on treatments that can lead to response but not at the risk of a patient’s quality of life.” 

Currently, Lowry’s platelets are in the low 400,000s, and she continues to receive Hydrea and Tibsovo. The married mother of two is back to enjoying time with her five grandchildren, traveling with high school girlfriends and doing yoga three days a week. 

“If you know you have a blood disease, you need to see a hematologist,” Lowry says. “You need to be in a supportive community because if I had been going to someone who was more knowledgeable about blood, I wouldn’t have suffered so long.”

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

Articles

Researchers may have uncovered new ways to help patients with accelerated-phase and blast-phase MPNs live longer by borrowing therapies from other blood cancers.

Novel Approaches Create a Bridge to Transplant in MPNs

In October 2011, Kristen Wiley found a pea-sized lump in her breast. Having had a clear mammogram just seven months earlier, she thought it would go away.

When the lumps were still there in December, Wiley decided to go to her doctor at Mayo Clinic in Jacksonville, Florida. “She said, ‘I’m sure it’s nothing, but let’s be safe and do another mammogram,’” Wiley recalls her doctor telling her. The doctor also performed an ultrasound and biopsy. In January 2012, Wiley, then 41 years old, received a diagnosis of triple-positive breast cancer, which meant her tumors were human epidermal growth factor receptor 2 HER2-positive, estrogen receptor (ER)-positive and progesterone receptor (PR)-positive. This means the treatment like hormonal or HER2 antibody therapies would not be effective, and that the tumor was likely to be more dangerous.

When Kristen Wiley was 41 years old, her menstrual cycles stopped immediately following her mastectomy. They had been regular up to that point.

“I was a picture of health,” she says. “No family history of breast cancer. I was very active and fit. It completely took us by surprise.” Wiley, who had a 3-year-old daughter, decided she would go “full throttle” with her treatment after learning how aggressive her disease was. Her cancer was stage 2, and three lymph nodes were affected by the disease. Wiley had a double mastectomy with reconstruction, and over a 14-month period she underwent 29 rounds of chemotherapy, 27 radiation treatments and five surgeries.

Immediately after her mastectomy, her menstrual cycles — which Wiley describes as regular until that point — stopped. She began to have hot flashes hourly, seven days a week. “I would go from fine to bright, cherry red and pouring sweat within five minutes,” Wiley, now 50, says. Throughout treatment, she continued to work full time as a senior managing director for a global financial technology company, but the menopause-induced hot flashes and mood swings were difficult to hide because they would spring up without warning.

"I was a picture of health. No family history of breast cancer. I was very active and fit. It completely took us by surprise." - Kristen Wiley.

For most women in the United States, the average age of menopause is 51. But, like Wiley, many women with breast cancer can be propelled into medical menopause following treatment for the disease. All women who have an oophorectomy, a surgery to remove both ovaries, will go into immediate and permanent menopause if they weren’t menopausal before the surgery because the ovaries are no longer there to produce estrogen. In addition, up to 40% of women under age 40 and anywhere from 70% to 90% of women over age 40 go into permanent menopause because of chemotherapy, according to breastcancer.org. For other women, the loss of ovarian function is temporary.

For patients who are premenopausal, “some of the chemo- therapies are toxic to the ovaries, and the older women are, the more likely these agents will cause ovarian failure,” says Dr. Stephanie Faubion, director of Mayo Clinic Women’s Health and medical director for The North American Menopause Society (NAMS). “Early menopause caused by surgery is rapid and results in a sudden and dramatic decline in estrogen levels. Women are often very symptomatic with hot flashes, night sweats, joint aches, mood disturbances and sleep disturbances.”

Other symptoms of menopause include anxiety, depression, fatigue, brain fog and weight gain. Women may also experience bone loss and vaginal dryness, which can lead to painful intercourse. Vaginal dryness usually occurs in the months after menopause onset, according to Faubion.

Rebecca Seago-Coyle says she felt isolated after experiencing a lack of desire and vaginal dryness, which she says took a toll on her relationship with her husband. “I was in my 30s and wanted an active sex life,” says Seago-Coyle, who received a stage 1 ER-positive/HER2-positive breast cancer diagnosis in 2010 when she was 35. At the same time, she learned she was BRCA2-positive — a gene mutation she inherited from her father. Women who have BRCA mutations are at an increased risk of certain cancers — most notably, breast and ovarian cancer — and for developing them at a younger age, while men with BRCA2 mutations are at increased risk for breast cancer.

Rebecca Seago-Coyle says she felt isolated after experiencing a lack of desire and vaginal dryness, which she says took a toll on her relationship with her husband.

Seago-Coyle’s cancer was labeled aggressive because of the grade and tumor size. She was treated with 12 weeks of Taxol (paclitaxel) and a year of Herceptin (trastuzumab). She also underwent bilateral mastectomy with reconstruction and had her ovaries removed to decrease changes of recurrence. “I don’t think anyone prepares you for menopause,” Seago-Coyle says. “Medically induced menopause in your 30s is different (from what) the average person goes through gradually. When it happens medically, it’s a jolt.”

All of these symptoms can be stressful, as they are constant reminders not only of what is happening to the body at that moment but also the cancer itself. They can reduce day-to-day quality of life, which can be difficult for someone to navigate.

“Hot flashes, mood changes, body image, self-esteem — all of these things that may naturally happen with menopause later in life are happening for some women much earlier, so this could be at a time when they’re thinking about having families, or have young children, or being in the workforce more, and the day-to-day can take a toll on people emotionally, mentally and physically,” says Lauren Chatalian, a licensed clinical social worker and women and children’s program manager for 

Seago-Coyle enjoys reading and practicing yoga every night before going to bed. It helps her to fight restless sleep — a side effect of menopause.

Hormonal therapies that suppress estrogen levels can also cause side effects of menopause. When Wiley began taking aromatase inhibitors (AIs), more of the symptoms kicked in. She was first put on Arimidex (anastrozole), but it caused weight gain, so she switched medications to Femara (letrozole). However, she then began to have severe bone pain.

“It was like someone took a hammer to my toes and fingers and crushed all my bones overnight,” Wiley remembers. “You would feel like you were (being hit with) a meat tenderizer. I can take a lot of pain, but not this much.”

Her oncologist switched her AI a third time to Aromasin (exemestane), but that also caused bone pain. Wiley went back on Arimidex, which she says caused her to gain 30 to 40 pounds. But the extra pounds were a trade-off for less pain.

“When we think of menopause, we think about middle adulthood. You’re diagnosed and experiencing mixed emotions, prepping for treatment, surgery — and it goes fast, it’s hard to slow down,” Chatalian says.

In facilitating support groups for CancerCare, Chatalian advises women with breast cancer who experience menopause related to cancer treatments to have a conversation with their medical team and their loved ones about the life-disrupting symptoms and let them help.

Seago-Coyle ended up needing additional support. “My medical team had the best intentions, but it’s also feeling comfortable enough to share,” she says. “It’s hard to explain to other people because they interpret it in different ways. When I was going through chemotherapy, I went to a support group and learned how to talk more openly. These women shared tips and tricks.”

In addition to support groups, Chatalian encourages self-care, such as focusing on stress relief, using relaxation techniques, reading or journaling.

To fight restless sleep, which Seago-Coyle attributes to menopause, she created a routine that involves reading and doing yoga every night before bed. She also takes a natural supplement with magnesium and an Advil PM, and she is in bed by 8 p.m.

Wiley turned to an informal support group — two friends who received breast cancer diagnoses after she received hers. In addition, she became active with The DONNA Foundation, which supports families who are trying to make ends meet financially following breast cancer, thanks to a friend who introduced her to the group. She runs in the foundation’s annual marathon to help raise money and awareness for the cause.

On the home front, Wiley switched to cooling pillows and mattresses, and she doesn’t leave the house without a handheld fan. “I carry two in my purse at all times,” she says.

Pharmacologic options can help reduce menopause symptoms. For instance, results of several studies have shown that medications such as Effexor (venlafaxine), Neurontin (gabapentin) and Oxytrol (oxybutynin) may reduce the frequency and intensity of hot flashes. The only drug approved by the Food and Drug Administration to treat hot flashes associated with menopause is Brisdelle (paroxetine), which is an antidepressant. “Many of the antidepressants have been studied for hot flash management, and none of them have much more than a 40% to 50% reduction in symptoms,” Faubion says. “These are not magic cures. They take the edge off hot flashes.”

Researchers in phase 3 clinical trials are investigating NK3 inhibitors, which are a promising new class of drugs that target neurons in the brain’s hypothalamus responsible for hot flashes. Specifically, they take aim at the neuron complex kisspeptin/neurokinin B/dynorphin, known as KNDy neurons. Study results have shown an approximate 90% reduction in hot flashes in a couple of days compared with placebo at 25% to 30%.

Alternative therapies such as hypnosis and cognitive behavioral therapy have evidence to support their use for hot flash management. And in some cases, acupuncture has been more effective than medication, according to Dr. Amy Tiersten, a professor and clinical director of breast medical oncology at Mount Sinai in New York City.

Nonhormonal lubricants and moisturizers are initially offered to women who have vaginal dryness. But if those don’t work, low-dose vaginal estrogen can sometimes be considered after breast cancer survivors consult with their oncologists. Vaginal dilator therapy, which gently stretches vaginal tissue, and pelvic floor exercises to stretch and relax pelvic muscles may boost pelvic blood circulation and help relieve discomfort with sexual activity.

In women who experience joint pain following treatment with AIs, Cymbalta (duloxetine) may be prescribed. Bone- strengthening medications, such as Zometa (zoledronic acid), are often suggested for women taking AIs. “Not only do these bone-strengthening agents protect your bones from the negative effect on bone density from the aroma- tase inhibitors, but some studies show they also reduce the risk of the breast cancer coming back,” Tiersten says.

Typically, most patients are on anti-estrogen therapy for at least five years, but it could be as long as 10 years. The decision is made by looking at risk of recurrence and how well the drug is tolerated, according to Tiersten.

Perhaps the most beneficial thing a patient can do is to find a physician who specializes in helping women through menopause. NAMS has an easy-to-navigate menopause practitioner finder on its website.

If patients want to address symptoms without medication, they can lean on resources available at their cancer center in addition to finding nonprofit organizations that offer support. For instance, CancerCare offers in-person and virtual support groups.

“This is going to be disruptive, and I don’t wish it on anyone. But your mental outlook is key to your success,” Wiley emphasizes.

And when those feelings of isolation creep in, Chatalian wants patients to remember they’re not alone.

“Take it one step at a time,” Chatalian says. “You are your best advocate. For any symptoms that arise, have a discussion with your medical team. Have questions prepared. And know there is support available for all the mixed emotions.”

Some breast cancer therapies and surgeries cause a reduction in estrogen levels, forcing many women immediately into menopause.

Breast Cancer Treatments Propel Many Women Into 'Rapid, Dramatic' Medical Menopause

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

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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.

Katie Kosko

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